Discussion
death, ®, CLI, PAD, amputation, ischemia, pain, T cell sensitization of the recipient, ulcer
ISCHEMIA, ULCERS, EPITHELIALIZATION, PAD, NEOVASCULARIZATION, ULCER
Patients with PAD require aggressive modification of risk factor, exercise rehabilitation, treatment with antiplatelet drugs, vasodilators, reconstruction of the blood circulation by endovascular interventions and bypass therapy [Various phases of randomized clinical trials have shown that cell therapy is a feasible option for CLI patients, using either intramuscular or intra-arterial (or combination of both) administration either by single or repeated administrations [In the current study, stem cell was injected intramuscularly into the gastrocnemius muscle which might have created local depots of stem cells in the ischemic muscle, which will increase neovascularization by cell-to-cell contact, cell trans-differentiation and paracrine activity in the ischemic area. The angiogenic effect of the cells may be related to their ability to induce vascular and muscular regeneration by paracrine factors secreted. The angiogenic factors secreted by these cells especially vascular endothelial growth factor (VEGF) likely contribute to the increase in blood flow as evidenced by increase in ASP and ABPI in this study. Further, animal studies have also shown that intramuscular cell therapy may contribute to regeneration by tissue integration and/or secretion of paracrine factors [In this present study, multiple intramuscular injections of stempeucel® showed statistical significant reduction of rest pain and ulcer size along with healing of ulcers in an accelerated fashion as compared to baseline. There was statistically significant increased blood flow to the ischemic limbs as evidenced by increased ABPI and ASP. The QoL of patients improved along with increase in TWD. We have included no-option patients (patients without revascularization options) in the study which has a high rate of limb loss and death. In this study, no major amputation and no mortality were seen in the one-year follow-up period (amputation-free survival) and this may be due to increased neovascularization due to paracrine factors which has rescued the tissues from critical ischemia.The mean time taken for complete epithelialization in our study was 435 days, while partial epithelization was observed within 375 days. Overall, the data suggest that more than 96% ulcers showed healing, which include more than 82% ulcers with complete healing. Such improvement in ulcer healing was also observed by Ponemone V et al. [Several preclinical and clinical studies have shown that administration of allogeneic MSCs in an unrelated mismatched allogeneic host does not stimulate the formation of allo-specific antibodies or lead to a T cell sensitization of the recipient to alloantigen in different animal models.