Delivery of Stem Cells and BMP-2 With Functionalized Self-Assembling Peptide Enhances Regeneration of Infarcted...

Stem cell transplantation is a promising therapeutic strategy for myocardial infarction (MI). However, engraftment, survival and differentiation of the transplanted stem cells in ischemic and inflammatory microenvironment are poor. We designed a novel self-assembly peptide (SAP) by modifying the peptide RADA16 with cell-adhesive motif and BMP-2 (bone morphogenetic protein-2)-binding motif. Effects of the functionalized SAP on adhesion, survival and differentiation of c-kit⁺ MSCs (mesenchymal stem cells) were examined. Myocardial regeneration, neovascularization and cardiac function were assessed after transplantation of the SAP loading c-kit⁺ MSCs and BMP-2 in rat MI models. The SAP could spontaneously assemble into well-ordered nanofibrous scaffolds. The cells adhered to the SAP scaffolds and spread well. The SAP protected the cells in the condition of hypoxia and serum deprivation. Following degradation of the SAP, BMP-2 was released sustainedly and induced c-kit⁺ MSCs to differentiate into cardiomyocytes. At four weeks after transplantation of the SAP loading c-kit⁺ MSCs and BMP-2, myocardial regeneration and angiogenesis were enhanced, and cardiac function was improved significantly. The cardiomyocytes differentiated from the engrafted c-kit⁺ MSCs were increased markedly. The differentiated cells connected with recipient cardiomyocytes to form gap junctions. Collagen volume was decreased dramatically. These results suggest that the functionalized SAP promotes engraftment, survival and differentiation of stem cells effectively. Local sustained release of BMP-2 with SAP is a viable strategy to enhance differentiation of the engrafted stem cells and repair of the infarcted myocardium.