A prosurvival and proangiogenic stem cell delivery system to promote ischemic limb regeneration

Abstract

Stem cell therapy is a promising strategy to restore blood perfusion and promote muscle regeneration in ischemic limbs. Yet its therapeutic efficacy remains low owing to the inferior cell survival under the ischemic environment of the injured limbs. To increase therapeutic efficacy, high rate of cell survival is essential, which current approaches do not support. In this work, we tested the hypothesis that a stem cell delivery system that can continuously release a prosurvival and proangiogenic growth factor will promote high rates of cell survival in the ischemic limbs. The prosurvival effect could augment cell survival before vascularization is established, while the proangiogenic effect could stimulate quick angiogenesis to achieve long-term cell survival. Meanwhile, the differentiation of stem cells into endothelial and myogenic lineages, and cell paracrine effects will enhance vascularization and muscle regeneration.

Design of Injectable Materials to Improve Stem Cell Transplantation

“…Xu et al designed a synthetic, injectable hydrogel with a PNIPAAM backbone that exhibited strong mechanical properties (~17 kPa) when raised to body temperature. The incorporation of the pro-survival factor basic fibroblast growth factor (bFGF) with the hydrogel improved MSC survival after intramuscular injection, as well as increased blood vessel density, limb perfusion, and muscle diameter [114]. …”

Effects of lentiviral transfection containing bFGF gene on the biological characteristics of rabbit BMSCs

“…BFGF is a member of the family of fibroblast growth factors, which plays an important role in cell proliferation and differentiation and is widely recognized as a growth factor and differentiation inducer in the field of stem cell research . Studies by Du et al have shown that bFGF significantly enhances the ability of BMSCs to proliferate, possesses the ability to maintain osteogenesis, and is effective in stimulating vascular regeneration in vivo and promotes stem cell survival in vivo . In the present study, bFGF gene was successfully introduced into BMSCs.…”

Efficient differentiation of vascular endothelial cells from dermal-derived mesenchymal stem cells induced by endothelial cell lines conditioned medium

“…The high mortality associated with cardiovascular and cerebrovascular diseases is mainly caused by vascular disfunctions. Vascular disfunctions is also the vital characteristic of atherosclerotic peripheral artery disease, that affects more than 27 million people in North American and Europe [1]. Compared to drugs and traditional surgical treatments, cell therapy is an advantageous approach for the treatment of vascular abnormalities.…”

“…Mesenchymal stem cells (MSCs) are adult stem cells derived from the mesoderm, with high self-renewal ability and multi-directional differentiation potential, abundant in organs and the interstitial connective tissue. It has been proven that this kind of cells can differentiate into ECs [1] and other types of mature cells, under certain conditions. Moreover, ECs derived from MSCs have better plasticity than adult ECs, as they can effectively upregulate markers associated with an arterial phenotype [5].…”

“…Basic fibroblast growth factor (bFGF) can inhibit apoptosis of ECs under ischemic conditions by activating the endothelial cell hypoxia-induced factor-1 pathway [10]. It has been shown that more cells differentiate into ECs and participate in blood vessel formation in the presence of bFGF [1]. Data from Leroux et al revealed that ex vivo hypoxic preconditioning of MSCs plays a unique role in the enhancement of vessel formation [11].…”