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

• Published in: Journal of the American Heart Association 2020-01, Vol.9 (2), p.e013784-e013784
• Main Authors: Chen, Youhu, Li, Congye, Li, Chengxiang, Chen, Jiangwei, Li, Yan, Xie, Huaning, Lin, Chen, Fan, Miaomiao, Guo, Yongzhen, Gao, Erhe, Yan, Wenjun, Tao, Ling
• Format: Article
• Language: English
• Subjects: 3D culture; Animals; Cardio‐Oncology Spotlight; Cell Survival; Cells, Cultured; Cellular Microenvironment; Collagen - chemistry; Cross-Linking Reagents - chemistry; Disease Models, Animal; Fibrosis; Gelatin - chemistry; Graft Survival; Hydrogels; Male; Mesenchymal Stem Cell Transplantation - methods; mesenchymal stem cells; Mice, Inbred C57BL; myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - surgery; Myocardium - pathology; Original Research; Rats, Sprague-Dawley; Recovery of Function; Time Factors; transglutaminase cross‐linked gelatin; Transglutaminases - chemistry; Ventricular Function, Left
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/jaha.119.013784

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.