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

Anish S Majumdar²  Arun Pherwani⁴  Naveen Anthony²  Sagar Krishnamurthy²  Sanjay Gottipamula²  Anjan Das²  Sanjay Desai¹  Rajiv Parakh³  Anoop Chullikana²  Pawan K Gupta² 

[1] Department of Vascular and Endovascular Surgery, MS Ramaiah Memorial Hospital, MSR Nagar, MSRIT Post, Bangalore, 560054, India;Stempeutics Research Pvt Ltd, Akshay Tech Park, No. 72 & 73, 2nd Floor, EPIP Zone, Phase I-Area, Whitefield, Bangalore, 560066, India;Department of Vascular Surgery, Medanta - The Medicity, Sector – 38, Gurgaon, Haryana, 122 001, India;Consultant Vascular Surgeon, University Hospital of North Staffordshire, Newcastle-under-Lyme, Stoke-on-Trent, United Kingdom, Newcastle, ST5 0QP, UK

关键词: Allogeneic;    Bone marrow;    ABPI;    Mesenchymal stem cells;    CLI;   

Others  :  827435
DOI  :  10.1186/1479-5876-11-143

 received in 2013-01-30, accepted in 2013-05-27,  发布年份 2013

【 摘 要 】

Background

Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI.

Methods

Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment – related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb.

Results

Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells.

Conclusion

BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies.

Trial registration

NIH website (http://www.clinicaltrials.gov/ct2/show/NCT00883870 webcite)

【 授权许可】

   
2013 Gupta et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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