Cardiomyogenic differentiation of human bone marrow‐derived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats

Abstract

Collagen is the major structural protein in myocardium and contributes to tissue strength and integrity, cellular orientation, and cell–cell and cell‐matrix interactions. Significant post‐myocardial infarction related loss of cardiomyocytes and cardiac tissue, and their subsequent replacement with fibrous scar tissue, negatively impacts endogenous tissue repair and regeneration capabilities. To overcome such limitations, tissue engineers are working toward developing a 3D cardiac patch which not only mimics the structural, functional, and biological hierarchy of the native cardiac tissue, but also could deliver autologous stem cells and encourage their homing and differentiation. In this study, we examined the utility of electrospun, randomly‐oriented, type‐I collagen nanofiber (dia = 789 ± 162 nm) mats on the cardiomyogenic differentiation of human bone marrow‐derived mesenchymal stem cells (BM‐MSC) spheroids, in the presence or absence of 10 μM 5‐azacytidine (aza). Results showed that these scaffolds are biocompatible and enable time‐dependent evolution of early (GATA binding protein 4: GATA4), late (cardiac troponin I: cTnI), and mature (myosin heavy chain: MHC) cardiomyogenic markers, with a simultaneous reduction in CD90 (stemness) expression, independent of aza‐treatment. Aza‐exposure improved connexin‐4 expression and sustained sarcomeric α‐actin expression, but provided only transient improvement in cardiac troponin T (cTnT) expression. Cell orientation and alignment significantly improved in these nanofiber scaffolds over time and with aza‐exposure. Although further quantitative in vitro and in vivo studies are needed to establish the clinical applicability of such stem‐cell laden collagen nanofiber mats as cardiac patches for cardiac tissue regeneration, our results underscore the benefits of 3D milieu provided by electrospun collagen nanofiber mats, aza, and spheroids on the survival, cardiac differentiation and maturation of human BM‐MSCs. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3303–3312, 2018.

Efficient cardiomyocyte differentiation of induced pluripotent stem cells on PLGA nanofibers enriched by platelet‐rich plasma

“…In another study, Li et al investigated the cardiomyocyte differentiation potential of the human iPSCs while cultured on the multi‐layered poly(D,L‐lactic‐co‐glycolic acid) nanofibers, and their results demonstrated that this scaffold could be considered as a potential framework for cardiac tissue engineering 31 . Increase in cardiomyocyte differentiation potential of embryonic stem cells (ESCs) cultured on PLGA‐collagen nanofibers and MSCs cultured on collagen nanofibers was reported previously by Prabhakaran et al 32 and Joshi et al, 33 respectively.…”

Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia–reperfusion injury via upregulation of splenic regulatory T cells

“…Results (17)(18)(19)(20). In particular, the role and potential of BM-MSCs in ameliorating MIRI has been previously demonstrated (21)(22)(23). It has been shown that BM-MSCs differentiate into cardiomyocytes under appropriate ex vivo culture conditions (22,23).…”

“…In particular, the role and potential of BM-MSCs in ameliorating MIRI has been previously demonstrated (21)(22)(23). It has been shown that BM-MSCs differentiate into cardiomyocytes under appropriate ex vivo culture conditions (22,23). Earlier animal studies reported that BM-MSCs transfusions promoted cardiomyocyte proliferation and angiogenesis (21).…”

Five Decades Later, Are Mesenchymal Stem Cells Still Relevant?

“…Such matrices can be worked into desired shapes using micromolding, microfluidics, electrostatic droplet extrusion, or bioprinting (Kim et al, 2019). MSC based scaffolds systems have been used for bone and cartilage regeneration (Kim et al, 2019), as well as for the reproduction of blood vessels (Pinnock et al, 2016), cardiac tissue (Rashedi et al, 2017;Ichihara et al, 2018;Joshi et al, 2018), and skeletal muscle (Witt et al, 2017). Optimal tissue replacement efficiency relies on the physical characteristics of the scaffolds (Alakpa et al, 2017;Jeon et al, 2017;Mouser et al, 2018), as each mechanical property can modify the fate of the transplanted cells.…”