Polymer Cell Surface Coating Enhances Mesenchymal Stem Cell Retention and Cardiac Protection

Mesenchymal stem cell (MSC) therapy has been widely tested in clinical trials to promote healing post-myocardial infarction. However, low cell retention and the need for a large donor cell number in human studies remain a key challenge for clinical translation. Natural biomaterials such as gelatin are ideally suited as scaffolds to deliver and enhance cell engraftment after transplantation. A potential drawback of MSC encapsulation in the hydrogel is that the bulky matrix may limit their biological function and interaction with the surrounding tissue microenvironment that conveys important injury signals. To overcome this limitation, we adopted a gelatin methacrylate (gelMA) cell-coating technique that photocross-links gelatin on the individual cell surface at the nanoscale. The present study investigated the cardiac protection of gelMA coated, hypoxia preconditioned MSCs (gelMA-MSCs) in a murine myocardial infarction (MI) model. We demonstrate that the direct injection of gelMA-MSC results in significantly higher myocardial engraftment 7 days after MI compared to uncoated MSCs. GelMA-MSC further amplified MSC benefits resulting in enhanced cardioprotection as measured by cardiac function, scar size, and angiogenesis. Improved MSC cardiac retention also led to a greater cardiac immunomodulatory function after injury. Taken together, this study demonstrated the efficacy of gelMA-MSCs in treating cardiac injury with a promising potential to reduce the need for donor MSCs through enhanced myocardial engraftment.