Combination BM-MSC with BM-MNC is better than BM-MNC alone in resolution of large ischemic ulcers: A phase ll/lll clinical randomized study.

  • Journal: Cytotherapy Volume 18, Issue 6, Supplement S21June 2016
  • Authors: H. Harunarashid¹ ∙ M. Mohd Idris¹ ∙ S. Chin² ∙ F. Mohamad Yusoff¹ ∙ S. Shahari¹ ∙ N. Amran@Azman² ∙ S. Cheong²˒³ ∙ S.S. Abdul Wahid¹˒⁴

Affiliation

  1. Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
  2. Cytopeutics, Selangor, Malaysia
  3. Tunku Abdul Rahman University, Selangor, Malaysia
  4. Cell Therapy Centre, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia

Background

We previously demonstrated that combination bone marrow derived cultured mesenchymal stromal cell (BM-MSC) with bone marrow derived unselected mononuclear cell (BM-MNC) may help induce angiogenesis in diabetic patients with critical limb ischemia. In this new randomized Phase II/III clinical trial, we compared autologous BM-MSC with BM-MNC (Group A) versus BM-MNC alone (Group B) in severe lower limb ulcers secondary to critical limb ischemia with the aim of avoiding amputations.

Methods

Seven consecutive patients were randomized and underwent bone marrow aspiration (BMA) to collect 500mls that was then centrifuged and separated to obtain the unselected BM-MNC fraction. Group A (N = 3) patients underwent intra-muscular injection of the BM-MNC 1 hour after BMA on the affected limb, followed by intra-muscular injection of in-vitro expanded BM-MSC. Group B (N = 4) patients underwent injection of BM-MNC after BMA only. One patient in Group B had ulcers on each leg.

Results

All patients tolerated the BMA and injection well. The ulcer size at baseline, 1 month, 2 months and 5 months were as follows: Group A (22.5±14.2 vs. 6.3±10.1, 2.5±3.5, 0.0±0.0cm²; p = 0.07) Group B (25.4±12.0 vs. 29.1±22.8, 45.2±41.7, 54.8±52.7cm²; p = 0.84). All ulcers in Group A were completely healed by 5 months irrespective of baseline size (10-38cm²). In Group B, 2 ulcers (both smaller than 20 cm²) resolved while 3 ulcers (all greater than 20cm²) enlarged in size. Digital subtraction angiography (DSA) showed restoration of peripheral blood flow in all Group A patients. However, there were no difference in ankle brachial index at baseline to end of follow-up within both groups.

Conclusion

We have demonstrated that BM-MSC with BM-MNC is superior to BM-MNC alone in the resolution of severe foot ulcer secondary to critical limb ischemia, particularly for large ulcers.

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