A cellular delivery system fabricated with autologous BMSCs and collagen scaffold enhances angiogenesis and perfusion in ischemic hind limb.

Although therapeutic cellular angiogenesis is effective for chronic ischemia, the optimal mode of cellular administration is still under exploration. This study aimed to develop a cellular delivery system to enhance the perfusion and angiogenesis in the ischemic hind limb. Collagen scaffold (CS) was prepared, and for morphology and toxicity analysis, bone marrow-derived mesenchymal stem cells (BMSCs) were isolated, expanded, filtrated, and seeded onto CS to construct BMSCs-CS. The ischemic hind limbs of rabbit models were implanted with autologous BMSCs-CS, CS, and autologous BMSCs; the untreated ischemic or normal animals were considered as the ischemic or normal control groups. Oxygen saturation parameters were regularly measured to determine the perfusion in the extremities. Histological examinations with hematoxylin and eosin immunostaining against von Willebrand factor and smooth muscle (SM) α-actin were performed for capillary and mature vessel evaluation. CS was a multiporous structure without cytotoxicity. At several intervals, the oxygen saturation ratio (OSR) in normal control was the highest. The OSRs in BMSCs-CS and CS were higher than that in BMSCs and ischemic control (p < 0.05); the OSR in BMSCs-CS group was higher than that in CS at 6 and 8 weeks (p < 0.05). The capillaries in BMSCs-CS and CS were higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The mature vessels in BMSCs-CS were higher than that in CS, BMSCs, and the ischemic or normal control (p < 0.05). The autologous cellular delivery system proved to be an effective approach for improving higher ischemic hind limb perfusion and angiogenesis as opposed to cellular therapy alone.