Therapeutic Performance of Hydrogel‐Derived Extracellular Wharton's Jelly Matrix and Wharton's Jelly Mesenchymal Stem Cells in Repairing Infarcted Myocardium of Ischemic Rats: a Preclinical Study

Following myocardial infarction (MI), progressive death of cardiomyocytes and subsequent loss of the extracellular matrix leads to drastic alterations in the structure and mechanical performance of the heart, thereby leading to infarct expansion and cardiac dysfunction. To compensate for the lack of reparative potency in infarcted hearts and to inhibit negative remodeling in the myocardium after MI, stem cell-based therapy in combination with hydrogels has emerged as a promising strategy to improve cardiac function recovery. In this study, a novel injectable hydrogel derived from decellularized Wharton's jelly extracellular matrix (DWJM) is prepared and examined the therapeutic performance of a combination of bioactive DWJM hydrogels and Wharton's jelly mesenchymal stem cells (WJMSCs) for myocardial repair in ischemic rats. In vitro examinations indicated that the DWJM hydrogel exhibited appropriate rheological performance and is capable of undergoing sol-gel transition at 37 °C. After intramyocardial injection in MI rats, DWJM-trapped WJMSCs significantly improved cardiac function recovery, reduced scar formation, and promoted cardiomyogenesis and microvascular renewal compared to WJMSCs or DWJM hydrogels alone. The results demonstrated that the DWJM hydrogel and WJMSCs synergistically promoted myocardial repair, which further confirmed the promising stem cell therapy using the bioactive ECM hydrogel.