PMID- 36484201 OWN - NLM STAT- MEDLINE DCOM- 20230227 LR - 20230227 IS - 0261-1929 (Print) IS - 0261-1929 (Linking) VI - 51 IP - 1 DP - 2023 Jan TI - Cardiac Transcription Regulators Differentiate Human Umbilical Cord Mesenchymal Stem Cells into Cardiac Cells. PG - 12-29 LID - 10.1177/02611929221143774 [doi] AB - 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, alpha-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. FAU - Shafique, Shumaila AU - Shafique S AD - 208246Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. FAU - Ali, Syeda Roohina AU - Ali SR AD - 208246Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. FAU - Rajput, Shafiqa Naeem AU - Rajput SN AD - 208246Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. FAU - Salim, Asmat AU - Salim A AD - 208246Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. FAU - Khan, Irfan AU - Khan I AUID- ORCID: 0000-0003-1878-7836 AD - 208246Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan. LA - eng PT - Journal Article DEP - 20221209 PL - England TA - Altern Lab Anim JT - Alternatives to laboratory animals : ATLA JID - 8110074 RN - 0 (Transcription Factors) RN - 0 (Troponin I) SB - IM MH - Humans MH - Cell Differentiation/physiology MH - *Myocardium/metabolism MH - Transcription Factors/metabolism MH - Troponin I/metabolism MH - *Mesenchymal Stem Cells/metabolism MH - Umbilical Cord/metabolism OTO - NOTNLM OT - cardiac OT - differentiation OT - gene expression OT - immunostaining OT - transduction OT - umbilical cord mesenchymal stem cells EDAT- 2022/12/10 06:00 MHDA- 2023/03/03 06:00 CRDT- 2022/12/09 04:38 PHST- 2022/12/10 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2022/12/09 04:38 [entrez] AID - 10.1177/02611929221143774 [doi] PST - ppublish SO - Altern Lab Anim. 2023 Jan;51(1):12-29. doi: 10.1177/02611929221143774. Epub 2022 Dec 9.