DMPE-PEG scaffold binding with TGF-β1 receptor enhances cardiomyogenic differentiation of adipose-derived stem cells

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.

Role of human adipose-derived stem cells (hADSC) on TGF-β1, type I collagen, and fibrosis degree in bladder obstruction model of Wistar rats

“…Smooth muscle regeneration was mainly achieved by paracine factors or by direct differentiation into new smooth muscle tissue by injecting SCs. The interaction of cell surface receptors, ligands, and short-range-acting molecules between differentiated and undifferentiated cells significantly contributes to stem cell differentiation [ 17 ].…”

An Update on Adipose‐Derived Stem Cells for Regenerative Medicine: Where Challenge Meets Opportunity

“…used a polyethylene glycol‐conjugated phospholipid derivative (DMPE‐PEG) as a scaffold to bind recombinant TGF‐ β 1 receptor I to the surface of ADSCs. [ 183 ] Their results showed that the cardiomyogenic differentiation of ADSCs was significantly promoted by enhancing Smad2/3 phosphorylation. In addition, genetic modification of ADSCs has offered a potential route for inducing their differentiation into cardiomyocytes.…”

Engineering the cardiac tissue microenvironment

“…Synthetic biomaterials may be tailored to have high mechanical properties, with little batch-to-batch variability and immunogenicity, but they have limited functionality and resemblance to the natural cardiac ECM [179]. Synthetic biomaterials used for cardiac regeneration include polyethylene glycol [93,209], poly(lactic acid) [210,211], poly(lactic-co-glycolic acid) (PLGA) [212], poly (N-isopropylacrylamide) [213], and poly (glycerol sebacate) [211,214], as well as conductive materials such as polypyrrole [204,206], carbon nanotubes [215,216], gold [217,218], carbon nanofibers [219], and MXene [189] nanoparticles.…”

“…Scaffolds, hydrogels High solubility, high manipulability, non-adhesive, non-toxic, highly stable [93,209] Poly(lactic acid) (PLA) Scaffolds, nanofibers Biocompatability, controllable degradation, ease of modification, non-toxic [210,211] Poly(lactic-coglycolic acid) (PLGA) Scaffolds, hydrogels Biocompatability, controllable biodegradability, ease of functionalization [212] Poly (Nisopropylacrylamide) (PIPAAm) Hydrogels Thermosensitivity, protein preservative, ease of conjugation to other substrates [213] Poly (glycerol sebacate) (PGS)…”