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

Abstract

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 ( ADSC s) were co‐cultured with Col‐Tgel in a 3‐dimensional system in vitro, and Col‐Tgel encapsulated ADSC s were observed using scanning electron microscopy and confocal microscopy. Vitality, proliferation, and migration of co‐cultured ADSC s were evaluated. In addition, mice were subjected to MI and were intramyocardially injected with ADSC s, Col‐Tgel, or a combination thereof. ADSC s engraftment, survival, cardiac function, and fibrosis were assessed. In vitro MTT and Cell Counting Kit‐8 assays demonstrated that ADSC s survive and proliferate up to 4 weeks in the Col‐Tgel. In addition, MTT and transwell assays showed that ADSC s migrate outside the edge of the Col‐Tgel sphere. Furthermore, when compared with ADSC s alone, Col‐Tgel‐encapsulated ADSC s significantly enhanced the long‐term retention and cardioprotective effect of ADSC s against MI ‐induced cardiac injury. Conclusions In the current study, we successfully established a 3‐dimensional co‐culture system using ADSC s and Col‐Tgel. The Col‐Tgel creates a suitable microenvironment for long‐term retention of ADSC s 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.

Adipose-Derived Stem Cells: Current Applications and Future Directions in the Regeneration of Multiple Tissues

“…LVEF: left ventricular ejection fraction; LVESD: left ventricular end-systolic diameter; LVEDD: left ventricular end-diastolic diameter. Adapted from a previous study [ 144 ], with permission.…”

“…T gel-ADSCs significantly increased the LVEF at 4 weeks after MI. Additionally, T gel-ADSCs significantly decreased the left ventricular end-systolic diameter (LVESD), but not the left ventricular end-diastolic diameter (LVEDD), at 4 weeks after MI when compared with PBS treatment ( Figure 6(c) ) [ 144 ]. Furthermore, the decellularized extracellular matrix created a favorable microenvironment for ADSCs in the infarct area, reducing fibrosis and increasing the LVEF [ 145 ].…”

Biomaterials Loaded with Growth Factors/Cytokines and Stem Cells for Cardiac Tissue Regeneration

“…ADSCs, which are the MSCs derived from adipose tissue, are shown to have several advantages over the bone marrow-derived MSCs. These include a more attractive cost and yield, a less invasive method for isolation, and a higher rate of cell growth [ 93 ]. In the study by Blocki and colleagues, injectable microcapsules made of agarose and ECM components were developed to enhance the survival of bone marrow-derived MSCs after their transplantation to rats with acute MI.…”

Cardiac Stem Cell-Loaded Delivery Systems: A New Challenge for Myocardial Tissue Regeneration

“…In this contest, nanotechnologies could help to reduce the current limitations associated to cell therapies. In particular, one of the most promising approaches is based on the in vitro cells’ loading into 3D-scaffolds, such as hydrogels or patches, to improve their engraftment in the injured site, reducing their clearance rate and increasing their differentiation potential [ 16 , 17 , 18 , 19 ].…”