DMPE-PEG scaffold binding with TGF-\u03b21 receptor enhances cardiomyogenic differentiation of adipose-derived stem cells

Fei Zhang,Yuhao Bian,Yuan Xie

doi:10.1186/s13287-018-1090-z

Abstract

BackgroundHeart failure has become a global health problem with increasing incidences worldwide. Traditional pharmacological treatments can delay but cannot reverse the underlying disease processes. The clinical application of myocardial tissue engineering represents a promising strategy because it features cell-based replacement therapies that replace partially or fully damaged cardiac tissues with in vitro-generated tissue equivalents. However, the effectiveness of this therapy is limited by poor viability and differentiation of the grafted cells. This limitation could be overcome by rapidly increasing the numbers of functional cardiomyocytes. In this study, we aimed to obtain functional myocardial tissue engineering seed cells with high proliferation and differentiation rates by combining 1,2-dimyristoyl-sn-glycero-3-phosphoethan-olamine-polyethylene glycol (DMPE-PEG) and recombinant transforming growth factor-β1 receptor I (rTGF-β1 RI), followed by binding to human adipose-derived stromal cells (hADSCs).MethodsTo induce higher expression level of TGF-β1 RI, DMPE-PEG was inoculated with rTGF-β1 RI to modify the surface of hADSCs. The differentiation ability and morphological characteristics of the modified hADSCs were examined in vitro and in vivo.ResultsThe caridiomyocartic differentiation ability of TGF-β1 RI-modified hADSCs was significantly enhanced, as indicated by elevated expression levels of the cardiac markers cardiac troponin T (cTnT) and α-smooth muscle actin (SMA) via increased phosphorylation of the Smad signaling pathway-related proteins.ConclusionOur findings provide new insights into stem cell transplantation therapy in myocardial tissue engineering.

Highlights

Heart failure has become a global health problem with increasing incidences worldwide
Culture and identification of human adipose-derived stromal cells (hADSCs) Based on previous literature reports, hADSCs were subsequently cultured after isolation from fat depots
After 2 weeks in culture, the hADSCs grew into clusters and exhibited a long spindle shape (Fig. 1c). hADSCs derived from the mesoderm have multi-lineage differentiation potentials and can differentiate into adipocyte, osteoblast, cardiomyocyte, and other cell types

Summary

Introduction

Heart failure has become a global health problem with increasing incidences worldwide. The effectiveness of this therapy is limited by poor viability and differentiation of the grafted cells This limitation could be overcome by rapidly increasing the numbers of functional cardiomyocytes. With the rapid developments of in vitro cell culture and tissue engineering technologies, myocardial tissue engineering provides new and exciting possibilities for the treatment of end-stage ischemic heart disease. The application of myocardial tissue engineering in end-stage ischemic heart diseases begins with the transplantation of cardiomyocytes [4]. The in situ construction of engineered myocardial tissue features a strategy where functional seed cells, such as cardiac muscle stem cells, bone marrow mesenchymal stem cells, and induced pluripotent stem cells, are transplanted into the heart together with bioactive molecules (including growth factors and drugs) in order to repair or replace damaged myocardial tissues [5]. The cells should have the potential to differentiate into mature functional cardiomyocytes both in vivo and in vitro [6]

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