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. 2018 Oct 31;10(10):CD012794.
doi: 10.1002/14651858.CD012794.pub2.

Stem cell therapy for treatment of thromboangiitis obliterans (Buerger's disease)

Daniel G Cacione  1 , Frederico do Carmo Novaes, Daniel H Moreno
Affiliations

Stem cell therapy for treatment of thromboangiitis obliterans (Buerger's disease)

Daniel G Cacione et al. Cochrane Database Syst Rev. .

Abstract

Background: Thromboangiitis obliterans, also known as Buerger's disease, is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Stem cell therapy is an option for patients with severe complications, such as ischemic ulcers or rest pain.

Objectives: To assess the effectiveness and safety of stem cell therapy in individuals with thromboangiitis obliterans (Buerger's disease).

Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 October 2017. The review authors searched the European grey literature OpenGrey Database, screened reference lists of relevant studies and contacted study authors.

Selection criteria: Randomized controlled trials (RCTs) or quasi-RCTs of stem cell therapy in thromboangiitis obliterans (Buerger's disease).

Data collection and analysis: The review authors (DC, DM, FN) independently assessed the studies, extracted data and performed data analysis.

Main results: We only included one RCT (18 participants with thromboangiitis obliterans) comparing the implantation of stem cell derived from bone marrow with placebo and standard wound dressing care in this review. We identified no studies that compared stem cell therapy (bone marrow source) versus stem cell therapy (umbilical cord source), stem cell therapy (any source) versus pharmacological treatment and stem cell therapy (any source) versus sympathectomy. Ulcer healing was assessed in the form of ulcer size. The mean ulcer area decreased more in the stem cell implantation group: from 5.04 cm2 (standard deviation (SD) 0.70) to 1.48 cm2 (SD 0.56) compared with the control group: mean ulcer size area decreased from 4.68 cm2 (SD 0.62) to 3.59 cm2 (SD 0.14); mean difference (MD) -2.11 cm2, 95% confidence interval (CI) -2.49 to -1.73; 1 study, 18 participants; very low-quality evidence. Pain-free walking distance showed more of an improvement in the stem cell implantation group: from mean of 38.33 meters (SD 17.68) to 284.44 meters (SD 212.12) compared with the control group: mean walking distance increased from 35.66 meters (SD 19.79) to 78.22 meters (SD 35.35); MD 206.22 meters, 95% CI 65.73 to 346.71; 1 study; 18 participants; very low-quality evidence.Outcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.The quality of evidence was classified as very low, with only one study, small numbers of participants, high risk of bias in many domains and missing information regarding tobacco exposure status.

Authors' conclusions: Very low-quality evidence suggests there may be an effect of the use of bone marrow-derived stem cells in the healing of ulcers and improvement in the pain-free walking distance in patients with Buerger's disease. High-quality trials assessing the effectiveness of stem cell therapy for treatment of patients with thromboangiitis obliterans (Buerger's disease) are needed.

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Conflict of interest statement

  1. DC: none known

  2. FN: none known

  3. DM: 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 Stem cell therapy (any source) versus any other modality of treatment: stem cell therapy (bone marrow source) versus placebo, Outcome 1 Ulcer size at 12 weeks.
1.2
1.2. Analysis
Comparison 1 Stem cell therapy (any source) versus any other modality of treatment: stem cell therapy (bone marrow source) versus placebo, Outcome 2 Pain‐free walking distance at 12 weeks.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD012794

References

References to studies included in this review

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):359‐99. - PubMed

References to studies excluded from this review

Dong 2013 {published data only}
    1. Dong Z, Chen B, Fu W, Wang Y, Guo D, Wei Z, et al. Transplantation of purified CD34+ cells in the treatment of critical limb ischemia. Journal of Vascular Surgery 2013;58(2):404‐11. - PubMed
Kawamoto 2009 {published data only}
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Lee 2012 {published data only}
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Matoba 2008 {published data only}
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Ra 2016 {published data only}
    1. Ra JC, Jeong EC, Kang SK, Lee SJ, Choi KH. A prospective, nonrandomized, no placebo‐controlled, phase I/II clinical trial assessing the safety and efficacy of intramuscular injection of autologous adipose tissue‐derived mesenchymal stem cells in patients with severe Buerger's Disease. Cell Medicine 2016;9(3):87‐102. [DOI: 10.3727/215517916X693069; NCT01302015] - DOI - PMC - PubMed

References to studies awaiting assessment

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. Chinese Journal of Reparative and Reconstructive Surgery 2007;21(7):675‐8. - PubMed
JPRN‐C000000330 {unpublished data only}
    1. JPRN‐C000000330. Peripheral blood mononuclear cell therapy in PAD patients with intermittent claudication randomized trial. upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000000377 (first received 15 February 2006).
JPRN‐UMIN000002280 {unpublished data only}
    1. JPRN‐UMIN000002280. Randomized controlled trial of G‐CSF‐mobilized peripheral blood mononuclear cells transplantation for the treatment of patients with peripheral arterial disease. upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000002791 (first received 1 August 2009).
Majumdar 2015 {published data only}
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NCT01446055 {unpublished 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/NCT01446055 (first received 4 October 2011).
Wen 2010 {published data only}
    1. Wen J, Huang P. Autologous peripheral blood mononuclear cells transplantation in treatment of 30 cases of critical limb ischemia: 3‐year safety follow‐up. Journal of Clinical Rehabilitative Tissue Engineering Research 2010;14(45):8526‐30.

References to ongoing studies

NCT02501018 {unpublished data only}
    1. NCT02501018. Study to assess the efficacy and safety of CLBS12 in patients with critical limb ischemia (CLI). clinicaltrials.gov/ct2/show/NCT02501018 (date first received 17 Juy 2015).

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