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Meta-Analysis
. 2018 Aug 29;8(8):CD010747.
doi: 10.1002/14651858.CD010747.pub2.

Autologous cells derived from different sources and administered using different regimens for 'no-option' critical lower limb ischaemia patients

S Fadilah Abdul Wahid  1 , Nor Azimah Ismail, Wan Fariza Wan Jamaludin, Nor Asiah Muhamad, Muhammad Khairul Azaham Abdul Hamid, Hanafiah Harunarashid, Nai Ming Lai
Affiliations
Meta-Analysis

Autologous cells derived from different sources and administered using different regimens for 'no-option' critical lower limb ischaemia patients

S Fadilah Abdul Wahid et al. Cochrane Database Syst Rev. .

Abstract

Background: Revascularisation is the gold standard therapy for patients with critical limb ischaemia (CLI). In over 30% of patients who are not suitable for or have failed previous revascularisation therapy (the 'no-option' CLI patients), limb amputation is eventually unavoidable. Preliminary studies have reported encouraging outcomes with autologous cell-based therapy for the treatment of CLI in these 'no-option' patients. However, studies comparing the angiogenic potency and clinical effects of autologous cells derived from different sources have yielded limited data. Data regarding cell doses and routes of administration are also limited.

Objectives: To compare the efficacy and safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients.

Search methods: The Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and trials registries (16 May 2018). Review authors searched PubMed until February 2017.

Selection criteria: We included randomised controlled trials (RCTs) involving 'no-option' CLI patients comparing a particular source or regimen of autologous cell-based therapy against another source or regimen of autologous cell-based therapy.

Data collection and analysis: Three review authors independently assessed the eligibility and methodological quality of the trials. We extracted outcome data from each trial and pooled them for meta-analysis. We calculated effect estimates using a risk ratio (RR) with 95% confidence interval (CI), or a mean difference (MD) with 95% CI.

Main results: We included seven RCTs with a total of 359 participants. These studies compared bone marrow-mononuclear cells (BM-MNCs) versus mobilised peripheral blood stem cells (mPBSCs), BM-MNCs versus bone marrow-mesenchymal stem cells (BM-MSCs), high cell dose versus low cell dose, and intramuscular (IM) versus intra-arterial (IA) routes of cell implantation. We identified no other comparisons in these studies. We considered most studies to be at low risk of bias in random sequence generation, incomplete outcome data, and selective outcome reporting; at high risk of bias in blinding of patients and personnel; and at unclear risk of bias in allocation concealment and blinding of outcome assessors. The quality of evidence was most often low to very low, with risk of bias, imprecision, and indirectness of outcomes the major downgrading factors.Three RCTs (100 participants) reported a total of nine deaths during the study follow-up period. These studies did not report deaths according to treatment group.Results show no clear difference in amputation rates between IM and IA routes (RR 0.80, 95% CI 0.54 to 1.18; three RCTs, 95 participants; low-quality evidence). Single-study data show no clear difference in amputation rates between BM-MNC- and mPBSC-treated groups (RR 1.54, 95% CI 0.45 to 5.24; 150 participants; low-quality evidence) and between high and low cell dose (RR 3.21, 95% CI 0.87 to 11.90; 16 participants; very low-quality evidence). The study comparing BM-MNCs versus BM-MSCs reported no amputations.Single-study data with low-quality evidence show similar numbers of participants with healing ulcers between BM-MNCs and mPBSCs (RR 0.89, 95% CI 0.44 to 1.83; 49 participants) and between IM and IA routes (RR 1.13, 95% CI 0.73 to 1.76; 41 participants). In contrast, more participants appeared to have healing ulcers in the BM-MSC group than in the BM-MNC group (RR 2.00, 95% CI 1.02 to 3.92; one RCT, 22 participants; moderate-quality evidence). Researchers comparing high versus low cell doses did not report ulcer healing.Single-study data show similar numbers of participants with reduction in rest pain between BM-MNCs and mPBSCs (RR 0.99, 95% CI 0.93 to 1.06; 104 participants; moderate-quality evidence) and between IM and IA routes (RR 1.22, 95% CI 0.91 to 1.64; 32 participants; low-quality evidence). One study reported no clear difference in rest pain scores between BM-MNC and BM-MSC (MD 0.00, 95% CI -0.61 to 0.61; 37 participants; moderate-quality evidence). Trials comparing high versus low cell doses did not report rest pain.Single-study data show no clear difference in the number of participants with increased ankle-brachial index (ABI; increase of > 0.1 from pretreatment), between BM-MNCs and mPBSCs (RR 1.00, 95% CI 0.71 to 1.40; 104 participants; moderate-quality evidence), and between IM and IA routes (RR 0.93, 95% CI 0.43 to 2.00; 35 participants; very low-quality evidence). In contrast, ABI scores appeared higher in BM-MSC versus BM-MNC groups (MD 0.05, 95% CI 0.01 to 0.09; one RCT, 37 participants; low-quality evidence). ABI was not reported in the high versus low cell dose comparison.Similar numbers of participants had improved transcutaneous oxygen tension (TcO₂) with IM versus IA routes (RR 1.22, 95% CI 0.86 to 1.72; two RCTs, 62 participants; very low-quality evidence). Single-study data with low-quality evidence show a higher TcO₂ reading in BM-MSC versus BM-MNC groups (MD 8.00, 95% CI 3.46 to 12.54; 37 participants) and in mPBSC- versus BM-MNC-treated groups (MD 1.70, 95% CI 0.41 to 2.99; 150 participants). TcO₂ was not reported in the high versus low cell dose comparison.Study authors reported no significant short-term adverse effects attributed to autologous cell implantation.

Authors' conclusions: Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.

PubMed Disclaimer

Conflict of interest statement

SFAW: none known. NAI: none known. WFWJ: none known. NAM: none known. MKAAH: none known. HH: none known. NML: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 1 Amputation rate.
1.2
1.2. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 2 Wound/ulcer healing: number of participants with healing ulcers.
1.3
1.3. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 3 Wound/ulcer healing: change in ulcer size.
1.4
1.4. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 4 Reduction in rest pain: number of participants with any reduction in rest pain score.
1.5
1.5. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 5 Reduction in rest pain: rest pain score.
1.6
1.6. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 6 Improvement in lower limb perfusion: number of participants with increased ABI.
1.7
1.7. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 7 Improvement in lower limb perfusion: ABI score.
1.8
1.8. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 8 Improvement in lower limb perfusion: TcO₂ reading in mmHg.
1.9
1.9. Analysis
Comparison 1 BM‐MNCs vs mPBSCs, Outcome 9 Improvement in ischaemic symptoms: PFWD in metres at 12 weeks.
2.1
2.1. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 1 Amputation rate.
2.2
2.2. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 2 Wound/ulcer healing: number of participants with healing ulcers.
2.3
2.3. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 3 Reduction in rest pain: rest pain score.
2.4
2.4. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 4 Improvement in lower limb perfusion: ABI score.
2.5
2.5. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 5 Improvement in lower limb perfusion: TcO₂ reading in mmHg.
2.6
2.6. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 6 Improvement in ischaemic symptoms: PFWT in minutes at 24 weeks.
2.7
2.7. Analysis
Comparison 2 BM‐MNCs vs BM‐MSCs, Outcome 7 Improvement in vascularity and blood supply: number of participants with increase in numbers of collateral vessels.
3.1
3.1. Analysis
Comparison 3 Low cell dose vs high cell dose, Outcome 1 Amputation rate.
4.1
4.1. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 1 Amputation rate.
4.2
4.2. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 2 Wound/ulcer healing: number of participants with healing ulcer.
4.3
4.3. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 3 Reduction in rest pain: number of participants with reduction in rest pain score.
4.4
4.4. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 4 Improvement in lower limb perfusion: number of participants with increased ABI.
4.5
4.5. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 5 Improvement in lower limb perfusion: ABI score.
4.6
4.6. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 6 Improvement in lower limb perfusion: number of participants with improved TcO₂ reading.
4.7
4.7. Analysis
Comparison 4 Route of injection: IM injection vs IA injection, Outcome 7 Improvement in vascularity and blood supply: number of participants with increase in numbers of collateral vessels.
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Update of

References

References to studies included in this review

Gu 2008 {published data only}
    1. Gu YQ, Zhang J, Guo LR, Qi LX, Zhang SW, Xu J, et al. Transplantation of autologous bone marrow mononuclear cells for patients with lower limb ischemia. Chinese Medical Journal 2008;121(11):963‐7. [PUBMED: 18706241] - PubMed
Huang 2007 {published data only}
    1. Huang PP, Yang XF, Li SZ, Wen JC, Zhang Y, Han ZC. Randomised comparison of G‐CSF‐mobilized peripheral blood mononuclear cells versus bone marrow‐mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans. Thrombosis and Haemostasis 2007;98(6):1335‐42. [PUBMED: 18064333] - PubMed
Klepanec 2012 {published data only}
    1. Klepanec A, Mistrik M, Altaner C, Valachovicova M, Olejarova I, Slysko R, et al. No difference in intra‐arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia. Cell Transplantation 2012;21(9):1909‐18. [PUBMED: 22472173] - PubMed
    1. Madaric J, Klepanec A, Mistrik M, Altaner C, Valachovicova M, Necpal R, et al. Autologous bone marrow cells transplantation in patients with advanced critical limb ischemia: no difference in intra‐arterial and intramuscular application. Journal of the American College of Cardiology 2011;57(14):E1473.
Losordo 2012 {published data only}
    1. Losordo DW, Kibbe MR, Mendelsohn F, Marston W, Driver VR, Sharafuddin M, et al. A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia. Circulation. Cardiovascular Interventions 2012;5(6):821‐30. [PUBMED: 23192920] - PMC - PubMed
Lu 2011 {published data only}
    1. Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow‐derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double‐blind, randomized, controlled trial. Diabetes Research and Clinical Practice 2011;92(1):26‐36. [PUBMED: 21216483] - PubMed
Van Tongeren 2008 {published data only}
    1. Tongeren RB, Hamming JF, Fibbe WE, Weel V, Frerichs SJ, Stiggelbout AM, et al. Intramuscular or combined intramuscular/intra‐arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. Journal of Cardiovascular Surgery 2008;49(1):51‐8. [PUBMED: 18212687] - PubMed
Zhang 2009 {published data only}
    1. Zhang HF, Zhao ZG, Zhang CL, Yuan HJ, Wang YF. Autologous transplantation of bone marrow stem cells versus peripheral blood stem cells for treatment of diabetic lower limb ischemia: a comparative study in 52 cases. Journal of Clinical Rehabilitative Tissue Engineering Research 2009;13(6):1109‐12.

References to studies excluded from this review

Afan 2015 {published data only}
    1. Afan S, Bitterli L, Buhler S, DiSanto S, Zwahlen M, Schmidlin K, et al. Endothelial progenitor cells as biological marker of peripheral arterial disease. Vasa‐European Journal of Vascular Medicine 2015;44(Suppl 88):59‐60. - PubMed
Amann 2008 {published data only}
    1. Amann B, Ludemann C, Ruckert R, Lawall H, Liesenfeld B, Schneider M, et al. Design and rationale of a randomized, double‐blind, placebo‐controlled phase III study for autologous bone marrow cell transplantation in critical limb ischemia: the BONe Marrow Outcomes Trial in Critical Limb Ischemia (BONMOT‐CLI). VASA. Zeitschrift fur Gefasskrankheiten 2008;37(4):319‐25. [PUBMED: 19003741] - PubMed
Amato 2012 {published data only}
    1. Amato B, Compagna R, Della Corte GA, Martino G, Bianco T, Coretti G, et al. Peripheral blood mono‐nuclear cells implantation in patients with peripheral arterial disease: a pilot study for clinical and biochemical outcome of neoangiogenesis. BMC Surgery 2012;12(Suppl 1):S1. [PUBMED: 23173612] - PMC - PubMed
Arai 2006 {published data only}
    1. Arai M, Misao Y, Nagai H, Kawasaki M, Nagashima K, Suzuki K, et al. Granulocyte colony‐stimulating factor: a noninvasive regeneration therapy for treating atherosclerotic peripheral artery disease. Circulation Journal 2006;70(9):1093‐8. [PUBMED: 16936417] - PubMed
Arici 2015 {published data only}
    1. Arici V, Perotti C, Fabrizio C, Fante C, Ragni F, Alessandrino F, et al. Autologous immuno magnetically selected CD133+ stem cells in the treatment of no‐option critical limb ischemia: clinical and contrast enhanced ultrasound assessed results in eight patients. Journal of Translational Medicine 2015;13:342. [PUBMED: 26526721] - PMC - PubMed
Barć 2006 {published data only}
    1. Barć P, Skóra J, Pupka A, Turkiewicz D, Dorobisz AT, Garcarek J, et al. Bone‐marrow cells in therapy of critical limb ischaemia of lower extremities ‐ own experience. Acta Angiologica 2006;12(4):155‐66.
Bartsch 2007 {published data only}
    1. Bartsch T, Brehm M, Zeus T, Kogler G, Wernet P, Strauer BE. Transplantation of autologous mononuclear bone marrow stem cells in patients with peripheral arterial disease (the TAM‐PAD study). Clinical Research in Cardiology 2007;96(12):891‐9. [PUBMED: 17694378] - PubMed
Benoit 2011 {published data only}
    1. Benoit E, O'Donnell TF Jr, Iafrati MD, Asher E, Bandyk DF, Hallett JW, et al. The role of amputation as an outcome measure in cellular therapy for critical limb ischemia: implications for clinical trial design. Journal of Translational Medicine 2011;9:165. [PUBMED: 21951607] - PMC - PubMed
    1. Iafrati MD, Hallett JW, Geils G, Pearl G, Lumsden A, Peden E, et al. Early results and lessons learned from a multicenter, randomized, double‐blind trial of bone marrow aspirate concentrate in critical limb ischemia. Journal of Vascular Surgery 2011;54(6):1650‐8. [PUBMED: 22019148] - PubMed
Bing 2009 {published data only}
    1. Bing C, De‐bin L, Zi‐wen L, You‐zao J, Fu‐hua W, Qi‐nan W, et al. Autologous bone marrow mesenchymal stem cell transplantation for treatment of diabetic foot following amplification in vitro. Journal of Clinical Rehabilitative Tissue Engineering Research 2009;13:6227‐30.
Bura 2014 {published data only}
    1. Bura A, Planat‐Benard V, Bourin P, Silvestre JS, Gross F, Grolleau JL, et al. Phase I trial: the use of autologous cultured adipose‐derived stroma/stem cells to treat patients with non‐revascularizable critical limb ischemia. Cytotherapy 2014;16(2):245‐57. [PUBMED: 24438903] - PubMed
Burt 2010 {published data only}
    1. Burt RK, Testori A, Oyama Y, Rodriguez HE, Yaung K, Villa M, et al. Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. Bone Marrow Transplantation 2010;45(1):111‐6. [PUBMED: 19448678] - PMC - PubMed
Capiod 2009 {published data only}
    1. Capiod JC, Tournois C, Vitry F, Sevestre MA, Daliphard S, Reix T, et al. Characterization and comparison of bone marrow and peripheral blood mononuclear cells used for cellular therapy in critical leg ischaemia: towards a new cellular product. Vox Sanguinis 2009;96(3):256‐65. [PUBMED: 19207166] - PubMed
Chochola 2008 {published data only}
    1. Chochola M, Pytlik R, Kobylka P, Skalicka L, Kideryova L, Beran S, et al. Autologous intra‐arterial infusion of bone marrow mononuclear cells in patients with critical leg ischemia. International Angiology 2008;27(4):281‐90. [PUBMED: 18677289] - PubMed
Choi 2012 {published data only}
    1. Choi ET, Geraghty P, Cooke C, Schechtman K, Link D, Chambers CM, Veeraswamy RK. Stem cell mobilization to treat severe peripheral artery disease (STEMPAD). Vascular Annual Meeting 2012:LB7.
    1. NCT00797056. Stem cell mobilization by G‐CSF to treat severe peripheral artery disease. clinicaltrials.gov/ct2/show/NCT00797056 (first received 25 November 2008).
Cobellis 2008 {published data only}
    1. Cobellis G, Silvestroni A, Lillo S, Sica G, Botti C, Maione C, et al. Long‐term effects of repeated autologous transplantation of bone marrow cells in patients affected by peripheral arterial disease. Bone Marrow Transplantation 2008;42(10):667‐72. [PUBMED: 18695661] - PubMed
Cobellis 2010 {published data only}
    1. Cobellis G, Botti C, Taddeo A, Silvestroni A, Lillo S, Ponte A, et al. Successful bone marrow transplantation reveals the lack of endothelial progenitor cells mobilization in a patient with critical limb ischemia: a case report. Transplantation Proceedings 2010;42(7):2816‐20. [PUBMED: 20832596] - PubMed
Darinskas 2017 {published data only}
    1. Darinskas A, Paskevicius M, Apanavicius G, Vilkevicius G, Labanauskas L, Ichim TE, et al. Stromal vascular fraction cells for the treatment of critical limb ischemia: a pilot study. Journal of Translational Medicine 2017;15(1):143. [PUBMED: 28629476] - PMC - PubMed
Das 2013 {published data only}
    1. Das AK, Bin Abdullah BJ, Dhillon SS, Vijanari A, Anoop CH, Gupta PK. Intra‐arterial allogeneic mesenchymal stem cells for critical limb ischemia are safe and efficacious: report of a phase I study. World Journal of Surgery 2013;37(4):915‐22. [PUBMED: 23307180] - PubMed
Dash 2009 {published data only}
    1. Dash NR, Dash SN, Routray P, Mohapatra S, Mohapatra PC. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow‐derived mesenchymal stem cells. Rejuvenation Research 2009;12(5):359‐66. [PUBMED: 19929258] - PubMed
De Angelis 2014 {published data only}
    1. Angelis B, Gentile P, Orlandi F, Bocchini I, Pasquali C, Agovino A, et al. Limb rescue: a new autologous‐peripheral blood mononuclear cells technology in critical limb ischemia and chronic ulcers. Tissue Engineering. Part C, Methods 2014;21(5):423‐35. [PUBMED: 25341088] - PubMed
Debin 2008 {published data only}
    1. Debin L, Youzhao J, Ziwen L, Xiaoyan L, Zhonghui Z, Bing C. Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Journal of Medical Colleges of PLA 2008;23(2):106‐15.
Dou 2015 {published data only}
    1. Dou Y, Zhao J, Zhang L, Wang X, Yuan H, Yuan C. A follow‐up study on autologous bone marrow mononuclear cells transplantation for critical lower arteriosclerosis obliterans in diabetic patients. Zhongguo Xiu fu Chong Jian Wai ke za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery 2015;29(7):893‐8. [PUBMED: 26540987] - PubMed
Doudar 2013 {published data only}
    1. Doudar N, El AM, Abdel SS. Stem cell implantation in the treatment of peripheral vascular disease. Vox Sang 2013;Suppl 1(105):290.
Du 2017 {published data only}
    1. Du JW, Wu T, Zhang K, Su BY, Lu CP, Wang WC, et al. Umbilical cord mesenchymal stem cells combined with bone marrow stem cells for treatment of lower limb ischemia [脐带间充质干细胞联合骨髓干细胞治疗下肢缺血]. Chinese Journal of Tissue Engineering Research 2017;21(1):82‐6.
Dubsky 2013 {published data only}
    1. Dubsky M, Jirkovska A, Bem R, Fejfarova V, Pagacova L, Sixta B, et al. Both autologous bone marrow mononuclear cell and peripheral blood progenitor cell therapies similarly improve ischaemia in patients with diabetic foot in comparison with control treatment. Diabetes/Metabolism Research and Reviews 2013;29(5):369‐76. [PUBMED: 23390092] - PubMed
Duong 2008 {published data only}
    1. Duong Van Huyen JP, Smadja DM, Bruneval P, Gaussem P, Dal‐Cortivo L, Julia P, et al. Bone marrow‐derived mononuclear cell therapy induces distal angiogenesis after local injection in critical leg ischemia. Modern Pathology 2008;21(7):837‐46. [PUBMED: 18487998] - PubMed
Flugelman 2017 {published data only}
    1. Flugelman MY, Halak M, Yoffe B, Schneiderman J, Rubinstein C, Bloom AI, et al. Phase Ib safety, two‐odse study of MultiGeneAngio in patients with chronic critical limb ischemia. Molecular Therapy 2017;25(3):816‐25. [PUBMED: 28143739] - PMC - PubMed
Franz 2011 {published data only}
    1. Franz RW, Parks A, Shah KJ, Hankins T, Hartman JF, Wright ML. Use of autologous bone marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease. Journal of Vascular Surgery 2009;50(6):1378‐90. [PUBMED: 19837539] - PubMed
    1. Franz RW, Shah KJ, Johnson JD, Pin RH, Parks AM, Hankins T, et al. Short‐ to mid‐term results using autologous bone‐marrow mononuclear cell implantation therapy as a limb salvage procedure in patients with severe peripheral arterial disease. Vascular and Endovascular Surgery 2011;45(5):398‐406. [PUBMED: 21669864] - PubMed
Frogel 2017 {published data only}
    1. Frogel M, Niven MJ, Galili O, Sivak G, Kafri E, Moshe M, et al. Adult stem/progenitor cells derived from peripheral blood as a personalized treatment for critical limb ischemia (CLI). Vascular 2017;25(2 Suppl 1):88.
Gabr 2011 {published data only}
    1. Gabr H, Hedayet A, Imam U, Nasser M. Limb salvage using intramuscular injection of unfractionated autologous bone marrow mononuclear cells in critical limb ischemia: a prospective pilot clinical trial. Experimental and Clinical Transplantation 2011;9(3):197‐202. [PUBMED: 21649569] - PubMed
Grossman 2016 {published data only}
    1. Grossman PM, Mohler ER 3rd, Roessler BJ, Wilensky RL, Levine BL, Woo EY, et al. Phase I study of multi‐gene cell therapy in patients with peripheral artery disease. Vascular Medicine (London, England) 2016;21(1):21‐32. [PUBMED: 26584888] - PubMed
Gu 2006 {published data only}
    1. Gu Y, Zhang J, Qi L. Effective autologous bone marrow stem cell dosage for treatment of severe lower limb ischemia. Zhongguo Xiu fu Chong Jian Wai ke za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery 2006;20(5):504‐6. [PUBMED: 16752834] - PubMed
Gu 2007 {published data only}
    1. Gu Y, Zhang J, Qi L. [Comparative study on autologous implantation between bone marrow stem cells and peripheral blood stem cells for treatment of lower limb ischemia]. Zhongguo Xiu fu Chong Jian Wai ke za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery 2007;21(7):675‐8. [PUBMED: 17694651] - PubMed
Gu 2017 {published data only}
    1. Gu Y, Guo L, Guo J, Dardik A, Zhang S, Tong Z, et al. Granulocyte colony‐stimulating factor improves the efficacy of autologous bone marrow‐derived mononuclear cell transplantation treatment for lower limb ischemia. International Angiology 2017;36(4):346‐53. [PUBMED: 27958690] - PubMed
Guo 2018 {published data only}
    1. Guo J, Guo L, Cui S, Tong Z, Dardik A, Gu Y. Autologous bone marrow‐derived mononuclear cell therapy in Chinese patients with critical limb ischemia due to thromboangiitis obliterans: 10‐year results. Stem Cell Research & Therapy 2018;9(1):43. [PUBMED: 29471870] - PMC - PubMed
Gupta 2013 {published data only}
    1. Gupta PK, Chullikana A, Parakh R, Desai S, Das A, Gottipamula S, et al. A double blind randomized placebo controlled phase I/II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia. Journal of Translational Medicine 2013;11:143. [PUBMED: 23758736] - PMC - PubMed
Gupta 2017 {published data only}
    1. Gupta PK, Chullikana A, Rajkumar M, Krishna M, Dutta S, Sarkar U, et al. Role of bone marrow derived allogeneic mesenchymal stromal cells (Stempeucel) in critical limb ischemia due to Buerger's disease‐efficacy and safety results of non‐randomized, open label, multicentric, dose ranging, phase II study in India. Cytotherapy 2014;16(4):S80‐1.
    1. Gupta PK, Krishna M, Chullikana A, Desai S, Murugesan R, Dutta S. Administration of adult human bone marrow‐derived, cultured, pooled, allogeneic mesenchymal stromal cells in critical limb ischemia due to Buerger's disease: phase II study report suggests clinical efficacy. Journal of Vascular Surgery 2017;66(4):1303. - PMC - PubMed
    1. Gupta PK, Krishna M, Chullikana A, Desai S, Murugesan R, Dutta S, et al. Administration of adult human bone marrow‐derived, cultured, pooled, allogeneic mesenchymal stromal cells in critical limb ischemia due to Buerger's disease: phase II study report suggests clinical efficacy. Stem Cells Translational Medicine 2017;6(3):689‐99. - PMC - PubMed
Harunarashid 2016 {published data only}
    1. Harunarashid H, Mohd Idris M, Chin S, Mohamad Yusoff F, Shahari S, Amran@Azman N, et al. Combination BM‐MSC with BM‐MNC is better than BM‐MNC alone in resolution of large ischemic ulcers: a phase II/III clinical randomised study. 22nd Annual ISCT Meeting 2016;18(6 Suppl):S21.
Heo 2016 {published data only}
    1. Heo SH, Park YS, Kang ES, Park KB, Do YS, Kang KS, et al. Early results of clinical application of autologous whole bone marrow stem cell transplantation for critical limb ischemia with Buerger's disease. Scientific Reports 2016;6:19690. [PUBMED: 26791280] - PMC - PubMed
Hernandez 2007 {published data only}
    1. Hernandez P, Cortina L, Artaza H, Pol N, Lam RM, Dorticos E, et al. Autologous bone‐marrow mononuclear cell implantation in patients with severe lower limb ischaemia: a comparison of using blood cell separator and Ficoll density gradient centrifugation. Atherosclerosis 2007;194(2):e52‐6. [PUBMED: 16982058] - PubMed
Higashi 2004 {published data only}
    1. Higashi Y, Kimura M, Hara K, Noma K, Jitsuiki D, Nakagawa K, et al. Autologous bone‐marrow mononuclear cell implantation improves endothelium‐dependent vasodilation in patients with limb ischemia. Circulation 2004;109(10):1215‐8. [PUBMED: 15007007] - PubMed
Holzinger 1994 {published data only}
    1. Holzinger C, Zuckermann A, Kopp C, Schollhammer A, Imhof M, Zwolfer W, et al. Treatment of non‐healing skin ulcers with autologous activated mononuclear cells. European Journal of Vascular Surgery 1994;8(3):351‐6. [PUBMED: 8013688] - PubMed
Hoshino 2007 {published data only}
    1. Hoshino J, Ubara Y, Hara S, Sogawa Y, Suwabe T, Higa Y, et al. Quality of life improvement and long‐term effects of peripheral blood mononuclear cell transplantation for severe arteriosclerosis obliterans in diabetic patients on dialysis. Circulation Journal 2007;71(8):1193‐8. [PUBMED: 17652880] - PubMed
Huang 2005 {published data only}
    1. Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony‐stimulating factor‐mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care 2005;28(9):2155‐60. [PUBMED: 16123483] - PubMed
    1. NCT00730561. Hematopoietic stem cell transplantation for the treatment of limb ischemia and diabetic neuropathy. clinicaltrials.gov/ct2/show/NCT00730561 (first received 8 August 2008).
Iafrati 2016 {published data only}
    1. Iafrati MD, O'Donnell Jr TF, Perler B, Illig KA, Hallett J, Woo K, et al. SS03. Bone marrow aspirate concentrate in critical limb ischemia: results of an abridged prospective randomized pivotal trial in no option CLI. Abstracts of the 2016 Vascular Annual Meeting, The Society for Vascular Surgery 2016;63(6 Suppl):47S.
Idei 2011 {published data only}
    1. Idei N, Soga J, Hata T, Fujii Y, Fujimura N, Mikami S, et al. Autologous bone‐marrow mononuclear cell implantation reduces long‐term major amputation risk in patients with critical limb ischemia: a comparison of atherosclerotic peripheral arterial disease and Buerger disease. Circulation. Cardiovascular Interventions 2011;4(1):15‐25. [PUBMED: 21205941] - PubMed
Ishida 2005 {published data only}
    1. Ishida A, Ohya Y, Sakuda H, Ohshiro K, Higashiuesato Y, Nakaema M, et al. Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia. Circulation Journal 2005;69(10):1260‐5. [PUBMED: 16195628] - PubMed
Iso 2010 {published data only}
    1. Iso Y, Soda T, Sato T, Sato R, Kusuyama T, Omori Y, et al. Impact of implanted bone marrow progenitor cell composition on limb salvage after cell implantation in patients with critical limb ischemia. Atherosclerosis 2010;209(1):167‐72. [PUBMED: 19748620] - PubMed
Kamata 2007 {published data only}
    1. Kamata Y, Takahashi Y, Iwamoto M, Matsui K, Murakami Y, Muroi K, et al. Local implantation of autologous mononuclear cells from bone marrow and peripheral blood for treatment of ischaemic digits in patients with connective tissue diseases. Rheumatology (Oxford, England) 2007;46(5):882‐4. [PUBMED: 17309890] - PubMed
Kawamoto 2009 {published data only}
    1. Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, et al. Intramuscular transplantation of G‐CSF‐mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single‐blinded, dose‐escalation clinical trial. Stem Cells 2009;27(11):2857‐64. [PUBMED: 19711453] - PubMed
Kinoshita 2012 {published data only}
    1. Kinoshita M, Fujita Y, Katayama M, Baba R, Shibakawa M, Yoshikawa K, et al. Long‐term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor‐mobilized CD34 positive cells in patients with critical limb ischemia. Atherosclerosis 2012;224(2):440‐5. [PUBMED: 22877866] - PubMed
Kirana 2012 {published data only}
    1. Kirana S, Stratmann B, Prante C, Prohaska W, Koerperich H, Lammers D, et al. Autologous stem cell therapy in the treatment of limb ischaemia induced chronic tissue ulcers of diabetic foot patients. International Journal of Clinical Practice 2012;66(4):384‐93. [PUBMED: 22284892] - PubMed
    1. NCT01065337. Induced wound healing by application of expanded bone marrow stem cells in diabetic patients with critical limb ischemia. clinicaltrials.gov/ct2/show/NCT01065337 (first received 9 February 200).
Kolvenbach 2010 {published data only}
    1. Kolvenbach R, Kreissig C, Cagiannos C, Afifi R, Schmaltz E. Intraoperative adjunctive stem cell treatment in patients with critical limb ischemia using a novel point‐of‐care device. Annals of Vascular Surgery 2010;24(3):367‐72. [PUBMED: 19896796] - PubMed
Kondo 2016 {published data only}
    1. Kondo K, Hayashida R, Shibata R, Murohara T. Therapeutic angiogenesis for critical limb ischemia by implantation of autologous adipose‐derived regenerative cells: a clinical pilot study. Circulation 2016;134(Suppl 1):A18595.
Kondo 2018 {published data only}
    1. Kondo K, Yanishi K, Hayashida R, Shintani S, Shibata R, Murotani K, et al. Long‐term clinical outcomes survey of bone marrow‐derived cell therapy in critical limb ischemia in Japan. Circulation Journal 2018;82(4):1168‐78. [PUBMED: 29386474] - PubMed
Lara‐Hernandez 2010 {published data only}
    1. Lara‐Hernandez R, Lozano‐Vilardell P, Blanes P, Torreguitart‐Mirada N, Galmes A, Besalduch J. Safety and efficacy of therapeutic angiogenesis as a novel treatment in patients with critical limb ischemia. Annals of Vascular Surgery 2010;24(2):287‐94. [PUBMED: 20142004] - PubMed
Lasala 2010 {published data only}
    1. Lasala GP, Silva JA, Gardner PA, Minguell JJ. Combination stem cell therapy for the treatment of severe limb ischemia: safety and efficacy analysis. Angiology 2010;61(6):551‐6. [PUBMED: 20498146] - PubMed
Lee 2012 {published data only}
    1. Lee HC, An SG, Lee HW, Park JS, Cha KS, Hong TJ, et al. Safety and effect of adipose tissue‐derived stem cell implantation in patients with critical limb ischemia: a pilot study. Circulation Journal 2012;76(7):1750‐60. [PUBMED: 22498564] - PubMed
Lenk 2005 {published data only}
    1. Lenk K, Adams V, Lurz P, Erbs S, Linke A, Gielen S, et al. Therapeutical potential of blood‐derived progenitor cells in patients with peripheral arterial occlusive disease and critical limb ischaemia. European Heart Journal 2005;26(18):1903‐9. [PUBMED: 15855189] - PubMed
Li 2013 {published data only}
    1. Li M, Zhou H, Jin X, Wang M, Zhang S, Xu L. Autologous bone marrow mononuclear cells transplant in patients with critical leg ischemia: preliminary clinical results. Experimental and Clinical Transplantation 2013;11(5):435‐9. [PUBMED: 23477421] - PubMed
Madaric 2016 {published data only}
    1. Madaric J, Klepanec A, Valachovicova M, Mistrik M, Bucova M, Olejarova I, et al. Characteristics of responders to autologous bone marrow cell therapy for no‐option critical limb ischemia. Stem Cell Research & Therapy 2016;7(1):116. [PUBMED: 27530339] - PMC - PubMed
Madaric 2017 {published data only}
    1. Madaric J, Valachovicova M, Paulis L, Pribojova J, Mateova R, Sebekova K, et al. Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia. Stem Cell Research & Therapy 2017;8(1):165. [PUBMED: 28697789] - PMC - PubMed
Maione 2013 {published data only}
    1. Maione C, Botti C, Coppola CA, Silvestroni C, Lillo S, Schiavone V, et al. Effect of autologous transplantation of bone marrow cells concentrated with the MarrowXpress system in patients with critical limb ischemia. Transplantation Proceedings 2013;45(1):402‐6. [PUBMED: 23375329] - PubMed
Majumdar 2015 {published data only}
    1. Majumdar AS, Balasubramanian S, Thej C, Rajkumar M, Krishna M, Dutta S, et al. A first of its kind phase II clinical trial in critical limb ischemia patients using bone marrow derived, pooled, allogeneic mesenchymal stromal cells (Stempeucel). Cytotherapy 2015; Vol. 17:S84.
Malyar 2014 {published data only}
    1. Malyar NM, Radtke S, Malyar K, Arjumand J, Horn PA, Kröger K, et al. Autologous bone marrow mononuclear cell therapy improves symptoms in patients with end‐stage peripheral arterial disease and reduces inflammation‐associated parameters. Cytotherapy 2014;16(9):1270‐9. - PubMed
Matoba 2009 {published data only}
    1. Matoba S, Tatsumi T, Murohara T. Long‐term clinical outcome after intramuscular implantation of bone barrow mononuclear cells (therapeutic angiogenesis by cell transplantation [TACT] Trial) in patients with chronic limb ischemia. American Heart Journal 2009;50(1):233. - PubMed
Matsui 2003 {published data only}
    1. Matsui K, Murakami Y, Yoshioka T, Muroi K, Kasuda H, Shimpo M, et al. Therapeutic angiogenesis by transplantation of autologous bone marrow and peripheral blood mononuclear cells in patients with peripheral arterial disease. International Journal of Angiology 2003;12:155–61.
Mohamed 2017 {published data only}
    1. Mohamed S, McInerney V, Dunne A, Hayat A, Krawczyk J, Naughton S, et al. Autologous mesenchymal stem cells as a novel therapy for no‐option critical limb ischemia: preliminary results of a phase 1 study. Cytotherapy 2017;19(5):S198.
    1. Mohamed S, McInerney V, Dunne A, Hayat A, Krawczyk J, Naughton S, et al. Autologous mesenchymal stem cells as a novel therapy for no‐option critical limb ischemia: preliminary results of a phase 1 study. Irish Journal of Medical Science 2017;186(Suppl 2):S82.
Mohammadzadeh 2013 {published data only}
    1. Mohammadzadeh L, Samedanifard SH, Keshavarzi A, Alimoghaddam K, Larijani B, Ghavamzadeh A, et al. Therapeutic outcomes of transplanting autologous granulocyte colony‐stimulating factor‐mobilised peripheral mononuclear cells in diabetic patients with critical limb ischaemia. Experimental and Clinical Endocrinology & Diabetes 2013;121(1):48‐53. [PUBMED: 23329572] - PubMed
Moriya 2009 {published data only}
    1. Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, et al. Long‐term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. Circulation. Cardiovascular Interventions 2009;2(3):245‐54. [PUBMED: 20031722] - PubMed
Motukuru 2008 {published data only}
    1. Motukuru V, Suresh KR, Vivekanand V, Raj S, Girija KR. Therapeutic angiogenesis in Buerger's disease (thromboangiitis obliterans) patients with critical limb ischemia by autologous transplantation of bone marrow mononuclear cells. Journal of Vascular Surgery 2008;48(6 Suppl):53S‐60S; discussion 60S. [PUBMED: 19084740] - PubMed
Murphy 2011 {published data only}
    1. Murphy MP, Lawson JH, Rapp BM, Dalsing MC, Klein J, Wilson MG, et al. Autologous bone marrow mononuclear cell therapy is safe and promotes amputation‐free survival in patients with critical limb ischemia. Journal of Vascular Surgery 2011;53(6):1565‐74.e1. [PUBMED: 21514773] - PMC - PubMed
Murphy 2017 {published data only}
    1. Murphy MP, Ross CB, Kibbe M, Kelso R, Sharafuddin M, Tzeng E, et al. Intramuscular injection of autologous bone marrow cells to prevent amputation in critical limb ischemia: the results of the phase III MOBILE trial. Abstracts of the 2017 Vascular Annual Meeting 2017;65(6 Suppl):131S‐2S.
Napoli 2008 {published data only}
    1. Napoli C, Farzati B, Sica V, Iannuzzi E, Coppola G, Silvestroni A, et al. Beneficial effects of autologous bone marrow cell infusion and antioxidants/L‐arginine in patients with chronic critical limb ischemia. European Journal of Cardiovascular Prevention and Rehabilitation 2008;15(6):709‐18. [PUBMED: 19050436] - PubMed
NCT00306085 {published data only}
    1. Cobellis G, Botti C, Taddeo A, Silvestroni A, Lillo S, Ponte A, et al. Successful bone marrow transplantation reveals the lack of endothelial progenitor cells mobilization in a patient with critical limb ischemia: a case report. Transplantation Proceedings 2010;42(7):2816‐20. [PUBMED: 20832596] - PubMed
    1. Maione C, Botti C, Coppola CA, Silvestroni C, Lillo S, Schiavone V, et al. Effect of autologous transplantation of bone marrow cells concentrated with the MarrowXpress system in patients with critical limb ischemia. Transplantation Proceedings 2013;45(1):402‐6. [PUBMED: 23375329] - PubMed
    1. NCT00306085. Autologous bone marrow cell treatment in peripheral atherosclerosis. clinicaltrials.gov/ct2/show/study/NCT00306085 (first received 22 March 2006).
    1. Napoli C, Farzati B, Sica V, Iannuzzi E, Coppola G, Silvestroni A, et al. Beneficial effects of autologous bone marrow cell infusion and antioxidants/L‐arginine in patients with chronic critical limb ischemia. European Journal of Cardiovascular Prevention and Rehabilitation 2008;15(6):709‐18. [PUBMED: 19050436] - PubMed
NCT00434616 {published data only}
    1. NCT00434616. Autologous bone marrow stem cell transplantation for critical, limb‐threatening ischemia (BONMOT). clinicaltrials.gov/ct2/show/NCT00434616 (first received 13 February 2007).
NCT00539266 {published data only}
    1. NCT00539266. Autologous bone marrow‐derived mononuclear cells for therapeutic arteriogenesis in patients with limb ischemia (ABC). clinicaltrials.gov/ct2/show/NCT00539266 (first received October 2007).
NCT00922389 {published data only}
    1. NCT00922389. A clinical trial on diabetic foot using peripheral blood derived stem cells for treating critical limb ischemia. clinicaltrials.gov/ct2/show/NCT00922389 (first received 17 June 2009).
NCT01049919 {published data only}
    1. NCT01049919. Safety and efficacy study of autologous concentrated bone marrow aspirate (cBMA) for critical limb ischemia (CLI) (MOBILE). clinicaltrials.gov/ct2/show/NCT01049919 (first received 15 January 2010).
NCT01245335 {published data only}
    1. NCT01245335. Bone marrow aspirate concentrate (BMAC) for treatment of critical limb ischemia (CLI). clinicaltrials.gov/ct2/show/NCT01245335 (first received 22 November 2010).
NCT01584986 {published data only}
    1. NCT01584986. Autologous angiogenic cell precursors (ACPs) for the treatment of peripheral artery disease. clinicaltrials.gov/ct2/show/NCT01584986 (first received 25 April 2012).
NCT02336646 {published data only}
    1. NCT02336646. Cell therapy with mesenchymal stem cell in ischemic limb disease. clinicaltrials.gov/ct2/show/NCT02336646 (first received 13 January 2015).
NCT03174522 {published data only}
    1. NCT03174522. The efficacy and safety of Rexmyelocel‐T to treat ischemic ulcers in subjects with CLI Rutherford category 5 and DM. clinicaltrials.gov/ct2/show/NCT03174522 (first received 2 June 2017).
NCT03214887 {published data only}
    1. NCT03214887. Autologous BMMNC combined with HA therapy for PAOD. clinicaltrials.gov/ct2/show/NCT03214887 (first received 12 July 2017).
NCT03304821 {published data only}
    1. NCT03304821. Granulocyte‐macrophage stimulating factor (GM‐CSF) in peripheral arterial disease. clinicaltrials.gov/ct2/show/NCT03304821 (first received 9 October 2017).
NCT03339973 {published data only}
    1. NCT03339973. Allogeneic ABCB5‐positive stem cells for treatment of PAOD. clinicaltrials.gov/ct2/show/NCT03339973 (first received 13 November 2017).
Nemcova 2017 {published data only}
    1. Nemcova A, Jirkovska A, Dubsky M, Bem R, Fejfarova V, Pysna A, et al. Serum levels of angiogenic cytokines in the assessment of vasculogenesis after autologous cell therapy in diabetic patients with critical limb ischaemia. Diabetologia. 2017; Vol. 60:S468.
Niven 2017 {published data only}
    1. Niven MJ, Sivak G, Kafri E, Moshe M, Galili O, Frogel M, et al. Adult stem/progenitor cells as a personalised treatment for peripheral vascular disease. Diabetologia. 2017; Vol. 60:S31.
Nizankowski 2005 {published data only}
    1. Nizankowski R, Petriczek T, Skotnicki A, Szczeklik A. The treatment of advanced chronic lower limb ischaemia with marrow stem cell autotransplantation. Kardiologia Polska 2005;63(4):351‐60; discussion 361. [PUBMED: 16273471] - PubMed
Ohtake 2017 {published data only}
    1. Ohtake T, Mochida Y, Ishioka K, Oka M, Maesato K, Moriya H, et al. Effect of autologous G‐CSF‐mobilized CD34+ cell transplantation in hemodialysis patients with critical limb ischemia. Nephrology Dialysis Transplantation 2017;32(Suppl 3):iii309.
Onodera 2011 {published data only}
    1. Onodera R, Teramukai S, Tanaka S, Kojima S, Horie T, Matoba S, et al. Bone marrow mononuclear cells versus G‐CSF‐mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: pooled analysis for long‐term prognosis. Bone Marrow Transplantation 2011;46(2):278‐84. [PUBMED: 20479708] - PubMed
Ozturk 2012 {published data only}
    1. Ozturk A, Kucukardali Y, Tangi F, Erikci A, Uzun G, Bashekim C, et al. Therapeutical potential of autologous peripheral blood mononuclear cell transplantation in patients with type 2 diabetic critical limb ischemia. Journal of Diabetes and Its Complications 2012;26(1):29‐33. [PUBMED: 22240264] - PubMed
Peeters 2016 {published data only}
    1. Peeters Weem SMO, Teraa M, Ruijter HM, Borst GJ, Verhaar MC, Moll FL. Quality of life after treatment with autologous bone marrow derived cells in no option severe limb ischemia. European Journal of Vascular and Endovascular Surgery 2016;51(1):83‐9. - PubMed
Perin 2011 {published data only}
    1. Perin EC, Silva G, Gahremanpour A, Canales J, Zheng Y, Cabreira‐Hansen MG, et al. A randomized, controlled study of autologous therapy with bone marrow‐derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia. Catheterization and Cardiovascular Interventions 2011;78(7):1060‐7. [PUBMED: 21594960] - PubMed
Perin 2017 {published data only}
    1. Perin EC, Murphy M, Cooke JP, Moye L, Henry TD, Bettencourt J, et al. Rationale and design for PACE: patients with intermittent claudication injected with ALDH bright cells. American Heart Journal 2014;168(5):667‐73. [PUBMED: 25440794] - PMC - PubMed
    1. Perin EC, Murphy MP, March KL, Bolli R, Loughran J, Yang PC, et al. Evaluation of cell therapy on exercise performance and limb perfusion in peripheral artery disease: the CCTRN PACE Trial (patients with intermittent claudication injected with ALDH bright cells). Circulation 2017;135(15):1417‐28. - PMC - PubMed
Pignon 2017 {published data only}
    1. NCT00904501. Bone marrow autograft in limb ischemia (BALI). clinicaltrials.gov/ct2/show/study/NCT00904501 (first received 19 May 2009).
    1. Pignon B, Sevestre MA, Kanagaratnam L, Pernod G, Stephan D, Emmerich J, et al. Autologous bone marrow mononuclear cell implantation and its impact on the outcome of patients with critical limb ischemia: results of a randomized, double‐blind, placebo‐controlled trial. Circulation Journal 2017;81(11):1713‐20. [PUBMED: 28603176] - PubMed
Ponemone 2017 {published data only}
    1. Ponemone V, Gupta S, Sethi D, Suthar M, Sharma M, Powell RJ, et al. Safety and effectiveness of bone marrow cell concentrate in the treatment of chronic critical limb ischemia utilizing a rapid point‐of‐care system. Stem Cells International 2017;2017:4137626. [PUBMED: 28194186] - PMC - PubMed
Poole 2013 {published data only}
    1. Poole J, Mavromatis K, Binongo JN, Khan A, Li Q, Khayata M, et al. Effect of progenitor cell mobilization with granulocyte‐macrophage colony‐stimulating factor in patients with peripheral artery disease: a randomized clinical trial. JAMA 2013;310(24):2631‐9. [PUBMED: 24247554] - PMC - PubMed
Powell 2012 {published data only}
    1. Powell RJ, Marston WA, Berceli SA, Guzman R, Henry TD, Longcore AT, et al. Cellular therapy with Ixmyelocel‐T to treat critical limb ischemia: the randomized, double‐blind, placebo‐controlled RESTORE‐CLI trial. Molecular Therapy 2012;20(6):1280‐6. [PUBMED: 22453769] - PMC - PubMed
Prochazka 2010 {published data only}
    1. Prochazka V, Gumulec J, Jaluvka F, Salounova D, Jonszta T, Czerny D, et al. Cell therapy, a new standard in management of chronic critical limb ischemia and foot ulcer. Cell Transplantation 2010;19(11):1413‐24. [PUBMED: 20529449] - PMC - PubMed
Rajagopalan 2003 {published data only}
    1. Rajagopalan S, Mohler E 3rd, Lederman RJ, Saucedo J, Mendelsohn FO, Olin J, et al. Regional angiogenesis with vascular endothelial growth factor (VEGF) in peripheral arterial disease: design of the RAVE trial. American Heart Journal 2003;145(6):1114‐8. [PUBMED: 12796772] - PubMed
Ruiz‐Salmeron 2011 {published data only}
    1. Ruiz‐Salmeron R, Cuesta‐Diaz A, Constantino‐Bermejo M, Perez‐Camacho I, Marcos‐Sanchez F, Hmadcha A, et al. Angiographic demonstration of neoangiogenesis after intra‐arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb ischemia. Cell Transplantation 2011;20(10):1629‐39. [PUBMED: 22289660] - PubMed
Saito 2007 {published data only}
    1. Saito Y, Sasaki K, Katsuda Y, Murohara T, Takeshita Y, Okazaki T, et al. Effect of autologous bone‐marrow cell transplantation on ischemic ulcer in patients with Buerger's disease. Circulation Journal 2007;71(8):1187‐92. [PUBMED: 17652879] - PubMed
Schiavetta 2012 {published data only}
    1. Schiavetta A, Maione C, Botti C, Marino G, Lillo S, Garrone A, et al. A phase II trial of autologous transplantation of bone marrow stem cells for critical limb ischemia: results of the Naples and Pietra Ligure Evaluation of Stem Cells study. Stem Cells Translational Medicine 2012;1(7):572‐8. [PUBMED: 23197862] - PMC - PubMed
Smadja 2012 {published data only}
    1. Smadja DM, Duong‐van‐Huyen JP, Dal Cortivo L, Blanchard A, Bruneval P, Emmerich J, et al. Early endothelial progenitor cells in bone marrow are a biomarker of cell therapy success in patients with critical limb ischemia. Cytotherapy 2012;14(2):232‐9. [PUBMED: 22040109] - PubMed
Subramaniyam 2009 {published data only}
    1. Subramaniyam V, Waller EK, Murrow JR, Manatunga A, Lonial S, Kasirajan K, et al. Bone marrow mobilization with granulocyte macrophage colony‐stimulating factor improves endothelial dysfunction and exercise capacity in patients with peripheral arterial disease. American Heart Journal 2009;158(1):53‐60.e1. [PUBMED: 19540392] - PubMed
Szabo 2013 {published data only}
    1. Szabo GV, Kovesd Z, Cserepes J, Daroczy J, Belkin M, Acsady G. Peripheral blood‐derived autologous stem cell therapy for the treatment of patients with late‐stage peripheral artery disease ‐ results of the short‐ and long‐term follow‐up. Cytotherapy 2013;15(10):1245‐52. [PUBMED: 23993298] - PubMed
Takagi 2011 {published data only}
    1. Takagi G, Miyamoto M, Tara S, Takagi I, Takano H, Yasutake M, et al. Controlled‐release basic fibroblast growth factor for peripheral artery disease: comparison with autologous bone marrow‐derived stem cell transfer. Tissue Engineering. Part A 2011;17(21‐22):2787‐94. [PUBMED: 21810028] - PubMed
Tateishi‐Yuyama 2002 {published data only}
    1. Tateishi‐Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, et al. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone‐marrow cells: a pilot study and a randomised controlled trial. Lancet 2002;360(9331):427‐35. [PUBMED: 12241713] - PubMed
Teraa 2014 {published data only}
    1. Teraa M, Fledderus JO, Rozbeh RI, Leguit RJ, Verhaar MC. Bone marrow microvascular and neuropathic alterations in patients with critical limb ischemia. Circulation Research 2014;114(2):311‐4. [PUBMED: 24218170] - PubMed
Teraa 2015 {published data only}
    1. Sprengers RW, Moll FL, Teraa M, Verhaar MC. Rationale and design of the JUVENTAS trial for repeated intra‐arterial infusion of autologous bone marrow‐derived mononuclear cells in patients with critical limb ischemia. Journal of Vascular Surgery 2010;51(6):1564‐8. [PUBMED: 20488328] - PubMed
    1. Teraa M, Sprengers RW, Schutgens RE, Slaper‐Cortenbach IC, Graaf Y, Algra A, et al. Effect of repetitive intra‐arterial infusion of bone marrow mononuclear cells in patients with no‐option limb ischemia: the randomized, double‐blind, placebo‐controlled rejuvenating endothelial progenitor cells via transcutaneous intra‐arterial supplementation (JUVENTAS) trial. Circulation 2015;131(10):851‐60. [PUBMED: 25567765] - PubMed
Tournois 2015 {published data only}
    1. Tournois C, Pignon B, Sevestre MA, Djerada Z, Capiod JC, Poitevin G, et al. Critical limb ischemia: thrombogenic evaluation of two autologous cell therapy products and biologic profile in treated patients. Transfusion 2015;55(11):2692‐701. [PUBMED: 26222701] - PubMed
Walter 2011 {published data only}
    1. NCT00282646. Safety and feasibility study of autologous bone marrow cell transplantation in patients with PAOD. clinicaltrials.gov/ct2/show/study/NCT00282646 (first received 27 January 2006).
    1. Walter DH, Krankenberg H, Balzer JO, Kalka C, Baumgartner I, Schluter M, et al. Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia: a randomized‐start, placebo‐controlled pilot trial (PROVASA). Circulation. Cardiovascular Interventions 2011;4(1):26‐37. [PUBMED: 21205939] - PubMed
Wang 2014 {published data only}
    1. Wang X, Jiang L, Wang X, Yin F, Li G, Feng X, et al. Combination of autologous transplantation of G‐CSF‐mobilized peripheral blood mononuclear cells and Panax notoginseng saponins in the treatment of unreconstructable critical limb ischemia. Annals of Vascular Surgery 2014;28(6):1501‐12. [PUBMED: 24632316] - PubMed
Wang 2017 {published data only}
    1. Wang SK, Green L, Babbey C, Wilson M, Motaganahalli R, Fajardo A, et al. Ethnic minorities with critical limb ischemia derive equal amputation risk reduction from autologous cell therapy compared to Caucasians. Journal of Vascular Surgery 2017;65(6):113S. - PubMed
    1. Wang SK, Green LA, Motaganahalli RL, Wilson MG, Fajardo A, Murphy MP. Rationale and design of the MarrowStim PAD Kit for the treatment of critical limb ischemia in subjects with severe peripheral arterial disease (MOBILE) trial investigating autologous bone marrow cell therapy for critical limb ischemia. Journal of Vascular Surgery 2017;65(6):1850‐7.e2. [PUBMED: 28390770] - PubMed
Wang 2018 {published data only}
    1. Wang SK, Green LA, Drucker NA, Motaganahalli RL, Fajardo A, Murphy MP. Rationale and design of the Clinical and Histologic Analysis of Mesenchymal stromal cells in amPutations (CHAMP) trial investigating the therapeutic mechanism of mesenchymal stromal cells in the treatment of critical limb ischemia. Journal of Vascular Surgery 2018;68(1):176‐81.e1. [PUBMED: 29395424] - PMC - PubMed
Wester 2008 {published data only}
    1. Wester T, Jorgensen JJ, Stranden E, Sandbaek G, Tjonnfjord G, Bay D, et al. Treatment with autologous bone marrow mononuclear cells in patients with critical lower limb ischaemia. A pilot study. Scandinavian Journal of Surgery 2008;97(1):56‐62. [PUBMED: 18450207] - PubMed
Wijnand 2018 {published data only}
    1. NCT03042572. Allogeneic mesenchymal stromal cells for angiogenesis and neovascularization in no‐option ischemic limbs (SAIL). clinicaltrials.gov/ct2/show/NCT03042572 (first received 3 February 2017).
    1. Wijnand JGJ, Teraa M, Gremmels H, Rhijn‐Brouwer FCC, Borst GJ, Verhaar MC. Rationale and design of the SAIL trial for intramuscular injection of allogeneic mesenchymal stromal cells in no‐option critical limb ischemia. Journal of Vascular Surgery 2018;67(2):656‐61. [PUBMED: 29242062] - PubMed
Yanishi 2017 {published data only}
    1. Yanishi K, Nakanishi N, Zen K, Ogata T, Nakamura T, Yamano T, et al. Long‐term clinical outcome of therapeutic angiogenesis by cell transplantation in patients with critical limb ischemia. European Heart Journal. 2017;38(Suppl 1):1080.
Zafarghandi 2010 {published data only}
    1. Zafarghandi MR, Ravari H, Aghdami N, Namiri M, Moazzami K, Taghiabadi E, et al. Safety and efficacy of granulocyte‐colony‐stimulating factor administration following autologous intramuscular implantation of bone marrow mononuclear cells: a randomized controlled trial in patients with advanced lower limb ischemia. Cytotherapy 2010;12(6):783‐91. [PUBMED: 20078390] - PubMed
Zhang 2016 {published data only}
    1. Zhang X, Lian W, Lou W, Han S, Lu C, Zuo K, et al. Transcatheter arterial infusion of autologous CD133(+) cells for diabetic peripheral artery disease. Stem Cells International 2016;2016:6925357. [PUBMED: 26981134] - PMC - PubMed
Zhao 2008 {published data only}
    1. Zhao ZG, Yuan HJ, Zhang HF, Zhang CL, Wang YF, Ma SP, et al. Combined transplantation of autologous peripheral blood and bone marrow stem cells for the treatment of diabetic lower limb ischaemia: randomized controlled trial. [Chinese]. Journal of Clinical Rehabilitative Tissue Engineering Research 2008;12(8):1464‐6.
Zhou 2017 {published data only}
    1. Zhou HM, Liu F, Yang AG, Guo YQ, Zhou YR, Gu YQ, et al. Efficacy, safety and influencing factors of intra‐calf muscular injection of bone marrow mononuclear cells in the treatment of type 2 diabetes mellitus‐induced lower extremity vascular disease. Experimental and Therapeutic Medicine 2017;14(5):5177‐85. [PUBMED: 29201234] - PMC - PubMed
Zhou 2017a {published data only}
    1. Zhou CH, Xu LL, Hao XX, Sun XJ, Guo MJ, Liu B. Autologous CD34+ cell transplantation promotes angiogenesis in older adult patients with atherosclerotic ischemia: study protocol for a prospective, single‐center, open‐label, randomized controlled clinical trial [外周血CD34+细胞自体移植促进老年动脉粥样性缺血肢体的血管新生：前瞻性、单中心、开放性、随机对照临床试验方案]. Chinese Journal of Tissue Engineering Research 2017;21(13):1998‐2002.

References to studies awaiting assessment

Gurunathan 2009 {published data only}
    1. Gurunathan Mani S, Raju R, Kuppu Sampath V. Multicentre randomised clinical trial on the role of autologous bone‐marrow aspirate‐concentrate (BMAC)/CD34/(EPC) in non‐reconstructable critically ischaemic limbs. The Vascular Society of Great Britain & Ireland Yearbook 2009. 2009:56.
Korymasov 2009 {published data only}
    1. Korymasov EA, Tiumina OV, Aiupov AM, Kazantsev AV, Rossiev VA, Mikheev GV, et al. Use of autologous progenitor cells of the bone marrow in treatment of patients with lower‐limb atherosclerosis obliterans. Angiologiia i Sosudistaia Khirurgiia = Angiology and Vascular Surgery 2009;15(3):28‐31. [PUBMED: 20092179] - PubMed
Molavi 2016 {published data only}
    1. Molavi B, Zafarghandi MR, Aminizadeh E, Hosseini SE, Mirzayi H, Arab L, et al. Safety and efficacy of repeated bone marrow mononuclear cell therapy in patients with critical limb ischemia in a pilot randomized controlled trial. Archives of Iranian Medicine 2016;19(6):388‐96. [PUBMED: 27293053] - PubMed
    1. NCT01480414. Side effects of 4 times bone marrow mononuclear transplantation in patients with ischemic lower limb. clinicaltrials.gov/ct2/show/NCT01480414 (first received 28 November 2011).
NCT00595257 {published data only}
    1. NCT00595257. Feasibility study of autologous bone marrow aspirate concentrate for treatment of CLI. clinicaltrials.gov/ct2/show/study/NCT00595257 (first received 16 January 2008).
NCT00987363 {published data only}
    1. NCT00987363. Intraarterial infusion of autologous bone marrow in diabetic patients with chronic ischemia of lower limbs (CLI) no revascularization. clinicaltrials.gov/ct2/show/study/NCT00987363 (first recieved 30 September 2009).
NCT02993809 {published data only}
    1. NCT02993809. Autologous transplantation of BM‐ECs with platelet‐rich plasma extract for the treatment of critical limb ischemia. clinicaltrials.gov/ct2/show/study/NCT02993809 (first received 15 December 2016).

References to ongoing studies

NCT00311805 {published data only}
    1. NCT00311805. Autologous CD34+ stem cell injection for severe intermittent claudication (leg pain). clinicaltrials.gov/ct2/show/study/NCT00311805 (first received 6 April 2006).
NCT00753025 {published data only}
    1. NCT00753025. Autologous bone marrow for lower extremity ischemia treating. clinicaltrials.gov/ct2/show/study/NCT00753025 (first received 16 September 2008).
NCT01257776 {published data only}
    1. NCT01257776. Human adipose derived mesenchymal stem cells for critical limb ischemia (CLI) in diabetic patients. clinicaltrials.gov/ct2/show/study/NCT01257776 (first received 10 December 2010).
NCT01408381 {published data only}
    1. NCT01408381. Intra‐arterial infusion of autologous bone marrow mononuclear cells in non‐diabetic patients with critical limb ischemia (CLI). clinicaltrials.gov/ct2/show/study/NCT01408381 (first received 3 August 2011).
NCT01446055 {published data only}
    1. NCT01446055. Safety and efficacy study of autologous BM‐MNC processed by two methods for treating patients with chronic limb ischemia. clinicaltrials.gov/ct2/show/study/NCT01446055 (first received 4 October 2011).
NCT01745744 {published data only}
    1. NCT01745744. Application of cell regeneration therapy with mesenchymal stem cells from adipose tissue in critical chronic ischemic syndrome of lower limbs (CLI) in nondiabetic patients. clinicaltrials.gov/ct2/show/study/NCT01745744 (first received 10 December 2012).
NCT02454231 {published data only}
    1. NCT02454231. Monocentric trial: stem cell emergency life threatening limbs arteriopathy (SCELTA). clinicaltrials.gov/ct2/show/NCT02454231 (first received 27 May 2015).

Additional references

Benoit 2013
    1. Benoit E, O'Donnell TF, Patel AN. Safety and efficacy of autologous cell therapy in critical limb ischemia: a systematic review. Cell Transplantation 2013;22(3):545‐62. - PubMed
Botti 2012
    1. Botti C, Maione C, Coppola A, Sica V, Cobellis G. Autologous bone marrow cell therapy for peripheral arterial disease. Stem Cells and Cloning: Advances and Applications 2012;5:5‐14. - PMC - PubMed
Conrad 2011
    1. Conrad MF, Crawford RS, Hackney LA, Paruchuri V, Abularrage CJ, Patel VI, et al. Endovascular management of patients with critical limb ischemia. Journal of Vascular Surgery 2011;53(4):1020‐5. - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG, editor(s). Chapter 9. Analysing data and undertaking meta‐analyses. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Dormandy 2000
    1. Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter‐Society Consensus (TASC). Journal of Vascular Surgery 2000;31(1 Pt 2):S1‐S296. [PUBMED: 10666287] - PubMed
Drescher 2006
    1. Drescher R, Haller S, Koster O, Rothenburg T, Titschert A. Standard‐protocol moving‐table magnetic resonance angiography for planning of interventional procedures in patients with peripheral vascular occlusive disease. Clinical Imaging 2006;30(6):382‐7. [PUBMED: 17101406] - PubMed
Durdu 2006
    1. Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone‐marrow mononuclear cell implantation for patients with Rutherford grade II‐III thromboangiitis obliterans. Journal of Vascular Surgery 2006;44(4):732‐9. - PubMed
Fadilah 2013
    1. Fadilah SA, Mohd‐Razif MI, Seery ZA, Nor‐Rafeah T, Wan‐Fariza WJ, Habsah A, et al. Predictors of the yield of mobilized peripheral blood CD34+ cells in HLA‐matched sibling donor. Transfusion and Apheresis Science 2013;49(3):583‐9. [PUBMED: 24012241] - PubMed
Fadini 2007
    1. Fadini GP, Agostini C, Sartore S, Avogaro A. Endothelial progenitor cells in the natural history of atherosclerosis. Atherosclerosis 2007;194(1):46‐54. - PubMed
Fadini 2010
    1. Fadini GP, Agostini C, Avogaro A. Autologous stem cell therapy for peripheral arterial disease meta‐analysis and systematic review of the literature. Atherosclerosis 2010;209(1):10‐7. [PUBMED: 19740466] - PubMed
Guyatt 1993
    1. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence‐Based Medicine Working Group. JAMA 1993;270(21):2598‐601. - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated 2011). The Cochrane Collaboration 2011. Available from handbook.cochrane.org.
Honold 2006
    1. Honold J, Lehmann R, Heeschen C, Walter DH, Assmus B, Sasaki K, et al. Effects of granulocyte colony stimulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arteriosclerosis Thrombosis and Vascular Biology 2006;26(10):2238‐43. - PubMed
Huang 2004
    1. Huang PP, Li SZ, Han MZ, Xiao ZJ, Yang RC, Qui LG, et al. Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities. Thrombosis and Haemostasis 2004;91(3):606‐9. - PubMed
Inaba 2002
    1. Inaba S, Egashira K, Komori K. Peripheral‐blood or bone‐marrow mononuclear cells for therapeutic angiogenesis?. Lancet 2002;360(9350):2083. - PubMed
Jarajapu 2010
    1. Jarajapu YP, Grant MB. The promise of cell‐based therapies for diabetic complications challenges and solutions. Circulation Research 2010;106(5):854‐69. - PMC - PubMed
Kaelin 2008
    1. Kaelin WG, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molecular Cell 2008;30(4):393‐402. - PubMed
Kawamura 2006
    1. Kawamura A, Horie T, Tsuda I, Abe Y, Yamada M, Egawa H, et al. Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs. Journal of Artificial Organs 2006;9(4):226‐33. - PubMed
Liew 2016
    1. Liew A, Bhattacharya V, Shaw J, Stansby G. Cell therapy for critical limb ischemia: a meta‐analysis of randomized controlled trials. Angiology 2016;67(5):444‐555. [PUBMED: 26195561] - PubMed
Liu 2012
    1. Liu FP, Dong JJ, Sun SJ, Gao WY, Zhang ZW, Zhou XJ, et al. Autologous bone marrow stem cell transplantation in critical limb ischemia: a meta‐analysis of randomized controlled trials. Chinese Medical Journal 2012;125(23):4296‐300. [PUBMED: 23217403] - PubMed
Liu 2015
    1. Liu Y, Xu Y, Fang F, Zhang J, Guo L, Weng Z. Therapeutic efficacy of stem cell‐based therapy in peripheral arterial disease: a meta‐analysis. PloS One 2015;10(4):e0125032. [PUBMED: 25923119] - PMC - PubMed
Miyamoto 2006
    1. Miyamoto K, Nishigami K, Nagaya N, Akutsu K, Chiku M, Kamei M, et al. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation 2006;114(24):2679‐84. - PubMed
Moazzami 2014
    1. Moazzami K, Moazzami B, Roohi A, Nedjat S, Dolmatova E. Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia. Cochrane Database of Systematic Reviews 2014, Issue 12. [DOI: 10.1002/14651858.CD008347.pub3] - DOI - PMC - PubMed
NGC 2012
    1. National Guideline Clearinghouse (NGC). Lower limb peripheral arterial disease: diagnosis and management. National Institute for Health and Clinical Excellence (NICE) 2012 Aug. 28, issue Clinical guideline no. 147.
Norgren 2007
    1. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, TASC II Working Group. Inter‐society consensus for the management of peripheral arterial disease (TASC II). Journal of Vascular Surgery 2007;45(Suppl S):S5‐67. - PubMed
Norgren 2010
    1. Norgren L, Hiatt WR, Dormandy JA, Hirsch AT, Jaff MR, Diehm C, et al. The next 10 years in the management of peripheral artery disease: Perspectives from the 'PAD 2009' conference. European Journal of Vascular and Endovascular Surgery 2010;40:375‐80. - PubMed
Pittenger 1999
    1. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284(5411):143‐7. - PubMed
Raval 2014
    1. Raval AN, Schmuck EG, Tefera G, Leitzke C, Ark CV, Hei D, et al. Bilateral administration of autologous CD133+ cells in ambulatory patients with refractory critical limb ischemia: lessons learned from a pilot randomized, double‐blind, placebo‐controlled trial. Cytotherapy 2014;16(12):1720‐32. [PUBMED: 25239491] - PMC - PubMed
RevMan 5.3 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Reyes 2002
    1. Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM. Origin of endothelial progenitors in human postnatal bone marrow. Journal of Clinical Investigation 2002;109(3):337‐46. - PMC - PubMed
Sasajima 1997
    1. Sasajima T, Kubo Y, Inaba M, Goh K, Azuma N. Role of infrainguinal bypass in Buerger's disease: an eighteen‐year experience. European Journal of Vascular and Endovascular Surgery 1997;13(2):186‐92. - PubMed
Schatteman 2004
    1. Schatteman GC, Awad O. Hemangioblasts, angioblasts, and adult endothelial cell progenitors. The Anatomical Record Part A. Discoveries in Molecular, Cellular, and Evolutionary Biology 2004;276(1):13‐21. - PubMed
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Vist GE, Higgins JP, Deeks JJ, Glasziou P, et al. on behalf of the Cochrane Applicability and Recommendations Methods Group. Chapter 12. Interpreting results and drawing conclusions. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Schünemann 2011a
    1. Schünemann HJ, Oxman AD, Higgins JP, Vist GE, Glasziou P, Guyatt GH, on behalf of the Cochrane Applicability and Recommendations Methods Group and the Cochrane Statistical Methods Group. Chapter 11. Presenting results and ‘Summary of findings’ tables. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Sultan 2014
    1. Sultan S, Hynes N. Critical appraisal of stem cell therapy in peripheral arterial disease: do current scientific breakthroughs offer true promise or false hope?. Journal of Biomedical Science and Engineering 2014;7:75‐85.
Sun 2015
    1. Sun X, Ying J, Wang Y, Li W, Wu Y, Yao B, et al. Meta‐analysis on autologous stem cell transplantation in the treatment of limb ischemia. International Journal of Clinical and Experimental Medicine 2015;8(6):8740‐8. [PUBMED: 26309525] - PMC - PubMed
Teraa 2013
    1. Teraa M, Sprengers RW, Graaf Y, Peters CE, Moll FL, Verhaar MC. Autologous bone marrow‐derived cell therapy in patients with critical limb ischemia: a meta‐analysis of randomized controlled clinical trials. Annals of Surgery 2013;258(6):922‐9. [PUBMED: 23426345] - PubMed
Wen 2011
    1. Wen Y, Meng L, Gao Q. Autologous bone marrow cell therapy for patients with peripheral arterial disease: a meta‐analysis of randomized controlled trials. Expert Opinion on Biological Therapy 2011;11(12):1581‐9. [PUBMED: 21973046] - PubMed

References to other published versions of this review

Abdul Wahid 2013
    1. Abdul Wahid SF, Ismail NA, Abdul Hamid MKA, Harunarashid H, Idris MAM, Muhamad NA, Lai NM. Different sources of autologous mononuclear cells and stem cells for critical lower limb ischaemia. Cochrane Database of Systematic Reviews 2013, Issue 9. [DOI: 10.1002/14651858.CD010747] - DOI - PMC - PubMed

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