Immobilization of insulin-like growth factor-1 onto thermosensitive hydrogels to enhance cardiac progenitor cell survival and differentiation under ischemic conditions

Abstract

Stem cell therapy is a promising approach to treat myocardial infarction. However, direct delivery of stem cells into hearts experiences poor cell engraftment and differentiation, due to ischemic conditions (low nutrient and oxygen) in the infarct hearts. Development of suitable cell carriers capable of supporting cell survival and differentiation under these harsh conditions is critical for improving the efficacy of current stem cell therapy. In this work, we created a family of novel cell carriers based on thermosensitive hydrogels and insulin-like growth factor 1 (IGF-1), and investigated if these cell carriers can improve cell survival and differentiation under ischemic conditions. The thermosensitive hydrogels were synthesized from N-isopropylacrylamide, acrylic acid, acrylic acid N-hydroxysuccinicimide ester, and 2-hydroxyethyl methacrylate-oligo(hydroxybutyrate). The hydrogel solutions can be readily injected through 26G needles, and can quickly solidify at 37 °C to form highly flexible hydrogels. IGF-1 was immobilized into the hydrogels in order to support long-term cell survival and differentiation. Different amount of IGF-1 was immobilized by using hydrogels with different content of N-hydroxysuccinicimide ester groups. Cardiosphere derived cells were encapsulated in the hydrogels and cultured under ischemic conditions. The results demonstrated that a significant improvement of cell survival and differentiation was achieved after IGF-1 immobilization. These IGF-1 immobilized hydrogels have the potential to improve cell survival and differentiation in infarct hearts.