Cardiac Transcription Regulators Differentiate Human Umbilical Cord Mesenchymal Stem Cells into Cardiac Cells. Issue 1 (January 2023)

• Record Type: Journal Article
• Authors: Shafique, Shumaila; Ali, Syeda Roohina; Rajput, Shafiqa Naeem; Salim, Asmat; Khan, Irfan
• Is Part Of: ATLA. Volume 51:Issue 1(2023)
• Page Start: 12
• Page End: 29
• Publication Date: 2023-01
• Subjects: cardiac -- differentiation -- gene expression -- immunostaining -- transduction -- umbilical cord mesenchymal stem cells; Laboratory animals -- Periodicals; 616.0273
• DOI: 10.1177/02611929221143774
• Languages: English
• ISSNs: 0261-1929

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.