Tailorable Hydrogel Improves Retention and Cardioprotection of Intramyocardial Transplanted Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice

BACKGROUND: Poor engraftment of intramyocardial stem cells limits their therapeutic efficiency against myocardial infarction (MI)‐induced cardiac injury. Transglutaminase cross‐linked Gelatin (Col‐Tgel) is a tailorable collagen‐based hydrogel that is becoming an excellent biomaterial scaffold for cellular delivery in vivo. Here, we tested the hypothesis that Col‐Tgel increases retention of intramyocardially‐injected stem cells, and thereby reduces post‐MI cardiac injury. METHODS AND RESULTS: Adipose‐derived mesenchymal stem cells (ADSCs) were co‐cultured with Col‐Tgel in a 3‐dimensional system in vitro, and Col‐Tgel encapsulated ADSCs were observed using scanning electron microscopy and confocal microscopy. Vitality, proliferation, and migration of co‐cultured ADSCs were evaluated. In addition, mice were subjected to MI and were intramyocardially injected with ADSCs, Col‐Tgel, or a combination thereof. ADSCs engraftment, survival, cardiac function, and fibrosis were assessed. In vitro MTT and Cell Counting Kit‐8 assays demonstrated that ADSCs survive and proliferate up to 4 weeks in the Col‐Tgel. In addition, MTT and transwell assays showed that ADSCs migrate outside the edge of the Col‐Tgel sphere. Furthermore, when compared with ADSCs alone, Col‐Tgel‐encapsulated ADSCs significantly enhanced the long‐term retention and cardioprotective effect of ADSCs against MI‐induced cardiac injury. CONCLUSIONS: In the current study, we successfully established a 3‐dimensional co‐culture system using ADSCs and Col‐Tgel. The Col‐Tgel creates a suitable microenvironment for long‐term retention of ADSCs in an ischemic area, and thereby enhances their cardioprotective effects. Taken together, this study may provide an alternative biomaterial for stem cell‐based therapy to treat ischemic heart diseases.