Composite hydrogel modified by IGF-1C domain improves stem cell therapy for limb ischemia.

Stem cell treatment for critical limb ischemia yields a limited therapeutic effect due to cell loss and dysfunction caused by local ischemic environment. Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell fate via mimicking the components of stem cell niche. Herein, we prepared a bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized with C domain peptide of IGF-1 (IGF-1C), and examined whether this hydrogel could augment stem cell survival and therapeutic potential. Our results showed that IGF-1C-modified hydrogel increased in vitro viability and pro-angiogenic activity of adipose-derived stromal cells (ADSCs). Moreover, co-transplantation of hydrogel and ADSCs into ischemic hindlimbs of mice effectively ameliorated blood perfusion and muscle regeneration, leading to superior limb salvage. These therapeutic effects can be ascribed to improved ADSC retention, angiopoientin-1 secretion and neovascularization, as well as reduced inflammatory cell infiltration. Additionally, hydrogel enhanced anti-fibrotic activity of ADSCs as evidenced by decreased collagen accumulation at late stage. Together, our findings indicate that composite hydrogel modified by IGF-1C could promote survival and pro-angiogenic capacity of ADSCs and thereby represents a feasible option for cell-based treatment for critical limb ischemia.