TY - JOUR
T1 - Cardiomyogenic differentiation of human bone marrow-derived mesenchymal stem cell spheroids within electrospun collagen nanofiber mats
AU - Joshi, Jyotsna
AU - Brennan, David
AU - Beachley, Vince
AU - Kothapalli, Chandrasekhar R.
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2018/12
Y1 - 2018/12
N2 - 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.
AB - 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.
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U2 - 10.1002/jbm.a.36530
DO - 10.1002/jbm.a.36530
M3 - Article
C2 - 30242963
AN - SCOPUS:85053711075
SN - 1549-3296
VL - 106
SP - 3303
EP - 3312
JO - Journal of Biomedical Materials Research - Part A
JF - Journal of Biomedical Materials Research - Part A
IS - 12
ER -