Cardiac Transcription Regulators Differentiate Human Umbilical Cord Mesenchymal Stem Cells into Cardiac Cells

Abstract

Stem cell-based therapy presents an attractive alternative to conventional therapies for degenerative diseases. Numerous studies have investigated the capability of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) to contribute to the regeneration of cardiomyocytes, and the results have encouraged further basic and clinical studies on the MSC-based treatment of cardiomyopathies. This study aimed to determine the potential of cardiomyogenic transcription factors in differentiating hUC-MSCs into cardiac-like cells in vitro. MSCs were isolated from umbilical cord tissue and were transduced with the transcription factor genes, GATA-4 and Nkx 2.5, via infection with lentiviruses, to promote differentiation into the cardiomyogenic lineage. Gene and protein expression were analysed with qPCR and immunocytochemical staining. After transduction, differentiated cardiac-like cells showed significant expression of cardiac genes and proteins, namely GATA-4, Nkx-2.5, cardiac troponin I (cTnI) and myosin heavy chain (MHC). The cardiomyogenic-induced group significantly overexpressed cardiac-specific genes ( GATA-4, Nkx-2.5, cTnI, MHC, α-actinin and Wnt2). Expression of the calcium channel gene was also significantly increased, while the sodium channel gene was downregulated in the transduced hUC-MSCs, as compared to non-transduced cells. The results suggest that GATA-4 and Nkx-2.5 interact synergistically in the activation of downstream cardiac transcription factors, demonstrating the functional convergence of hUC-MSC differentiation into cardiac-like cells. These findings could potentially be utilised in the efficient production of cardiac-like cells from stem cells; these cardiac-like cells could then be used in various applications, such as for in vivo implantation in infarcted myocardium, and for drug screening in toxicity testing.

Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine

“…Study investigated that MSCs are capable to differentiate into osteogenic, chondrogenic, and adipogenic lineages. However, current techniques for inducing differentiation have been improved, and MSCs derived from different tissue sources can be differentiated into any type of body cell[ 64 ]. It has been found that after 21 d of induction with osteogenic, chondrogenic, and adipogenic induction media, the MSCs differentiated, as confirmed by the presence of calcium deposits, proteoglycan formation, and oil droplets, respectively[ 22 ].…”

Editorial

“…The recent, rapid expansion of stem cell-based research, and its successful translation into therapy, presents an opportunity for significant advancements in developing novel treatments in the future. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) that may contribute to the regeneration of cardiomyocytes, were the subject of the study by Shafique et al 3 By overexpressing GATA-4 and Nkx-2.5 in hUC-MSCs, following lentiviral gene transduction, the authors demonstrated the potential of these factors to act synergistically in the activation of downstream cardiac transcription factors, facilitating the differentiation of hUC-MSCs into cardiac-like cells in vitro . Such findings may be useful for developing in vivo treatments following myocardial infarction.…”