Promoting Cardiomyogenesis of hBMSC with a Forming Self-Assembly hBMSC Microtissues/HA-GRGD/SF-PCL Cardiac Patch Is Mediated by the Synergistic Functions of HA-GRGD.

Abstract

Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces. The results show that the proliferations of hBMSC on HGSP patches significantly exceed those on the other patches, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Notably, the formation of 5-aza inducing cardiomyogenic differentiations of hBMSCMT/HGSP patches is observed with typical sizes of ≈317 μm wide and 26 μm high. The cardiomyogenesis of hBMSCMT/HGSP patches including the expressions of cardiac-specific genes (e.g., Gata4) and proteins (e.g., connexin43 (CX43)) significantly exceeds those of hBMSC monolayer on the HSP and SP patches. Promoting in vitro cardiomyogenesis of hBMSC with forming cardiomyogenic differentiation of hBMSCMT/HGSP hybrid patch is possibly mediated by the synergistic functions of HA-GRGD on enhancing the activity of F-actin. The hBMSCMT/HGSP cardiac patch may be further employed to cardiac tissue engineering.