Introduction
lower limb amputation, PAD, peripheral artery disease, diabetic, ischemic cardiovascular disease, diabetes
PAD, DIABETES, PERIPHERAL ARTERY DISEASE, CHRONIC LIMB-THREATENING ISCHEMIA
Chronic limb-threatening ischemia (CLTI) constitutes the most severe condition of peripheral artery disease (PAD) [PAD and diabetes are main risk factors for lower limb amputation [Therefore, new biological revascularization options to improve CLTI are under study, among which cell-based therapy offers the greatest hope for these patients. These therapies have provided new prospects for patients without conventional, open, or endovascular therapeutic options for two decades by potentially enabling neo-angiogenesis.The rationale behind using cell-based therapy as a treatment for ischemic cardiovascular disease was motivated by the discovery that human blood contained progenitor cells that mobilize to ischemic tissues and augmented angiogenesis [These EPCs were initially thought to promote angiogenesis by forming new vessels as they actively homed to ischemic areas after injection. They contribute to vascular regeneration by differentiating into mature endothelial cells (EC), forming a structural component of capillaries and secreting angiogenic factors. However, several studies have demonstrated that diabetic patients showed a reduced number of EPCs, that are dysfunctional, and the cultured EPCs presented profound functional impairment [Recently, a number of researchers have conducted clinical studies on treating CLTI with other stem cells. Indeed, a recent study by Khodayari et al. reveals that endometrial tissue can be considered a suitable candidate for isolating new safe, effective, and feasible multipotent stem cells (endometrial-derived stem cells (EnSCs)) for limb regeneration. EnSCs can generate diverse types of cells, essential for limb reconstruction, including endothelial cells, smooth muscle cells, muscle cells, and even peripheral nervous system populations (Khodayari, 2022 #70).On the other hand, the most common stem cells include CD34In our present work, we conducted a pilot study to determine the safety and beneficial therapeutic effect of auto-BM-MNC and allogeneic Wharton jelly-derived mesenchymal stem cells (allo-WJ-MSCs) as treatments for diabetic patients with CLTI. Briefly, we compared the used of one dose of auto-BM-MNC, one dose of allo-WJ-MSCs, or one dose of placebo solution (saline solution with 2% of autologous serum), which were injected into the periadventitial layer of the arterial walls under eco-Doppler guidance. In addition, the (i) Rutherford’s classification, (ii) TcPO