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. 2014 Dec 19;2014(12):CD008347.
doi: 10.1002/14651858.CD008347.pub3.

Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia

Kasra Moazzami  1 , Bobak Moazzami, Aria Roohi, Saharnaz Nedjat, Elena Dolmatova
Affiliations

Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia

Kasra Moazzami et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011.

Objectives: To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI).

Search methods: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1).

Selection criteria: We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication.

Data collection and analysis: Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author.

Main results: Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007).

Authors' conclusions: The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.

PubMed Disclaimer

Conflict of interest statement

KM: none known. BM: none known. AR: none known. SN: none known. ED: 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.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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References to studies excluded from this review

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Gupta 2013 {published data only}
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Gurunathan 2009 {published data only}
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Hernandez 2007 {published data only}
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Higashi 2010 {published data only}
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Holzinger 1994 {published data only}
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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
Iafrati 2011 {published data only}
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JUVENTAS {published data only}
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Lasala 2011 {published data only}
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Li 2013 {published data only}
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Lu 2011 {published data only}
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Madaric 2011 {published data only}
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    1. Madaric JK. Higher CD34+ cells concentration and lower degree of inflammation are associated with better therapeutic response to autologous bone marrow cells application in patients with critical limb ischemia. Journal of the American College of Cardiology 2011;58:B150.
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 and Diabetes 2013;121(1):48‐53. - PubMed
Napoli 2008 {published data only}
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NCT00282646 {published data only}
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NCT00498069 {published data only}
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NCT00539266 {published data only}
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NCT00595257 {published data only}
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NCT00616980 {published data only}
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NCT00904501 {published data only}
    1. NCT00904501. Bone marrow autograft in limb ischemia (BALI). www.clinicaltrials.gov/show/NCT00904501 (accessed November 2009).
NCT00913900 {published data only}
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NCT00922389 {published data only}
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NCT00955669 {published data only}
    1. NCT00955669. Comparison of autologous mesenchymal stem cells and mononuclear cells on diabetic critical limb ischemia and foot ulcer. www.clinicaltrials.gov/ct2/show/NCT00955669?term=nct00955669&rank=1 (accessed October 2014).
NCT01049919 {published data only}
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NCT01245335 {published data only}
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Ozturk 2012 {published data only}
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Pawan 2012 {published data only}
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Perin 2011 {published data only}
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RESTORE‐CLI Trial {published data only}
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Smadja 2012 {published data only}
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Takagi 2011 {published data only}
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Tateishi‐Yuyama 2002 {published data only}
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Van Huyen 2008 {published data only}
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References to other published versions of this review

Moazzami 2011
    1. Moazzami K, Majdzadeh R, Nedjat S. Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD008347.pub2] - DOI - PubMed

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