In Vitro Differentiation of Endometrium Stem Cells into Cardiomyocytes: The Putative Effect of miR-۱۷-۵p, miR-۲۶b-۵p, miR-۳۲-۵p, and SMAD۶

Background: The important role of SMAD۶ and several microRNAs (miRNAs), such as miR-۱۷-۵p, miR-۲۶b-۵p, and miR-۳۲-۵p, has been demonstrated in controlling the proliferation and differentiation of cardiomyocytes (CMs). Hence, this study was designed to assess the role of these regulatory factors in cardiac cell generation from human endometrium-derived mesenchymal stem cells (hEMSCs). Methods: To induce transdifferentiation into CMs, hEMSCs were treated with a cardiac-inducing medium containing ۵-azacytidine and bFGF for ۳۰ days. Immunofluorescence staining and qRT-PCR, respectively, were used to measure the protein levels of SMAD۶ and the mRNA expression of SMAD۶ and the three miRNAs every six days. Results: Our findings demonstrated the mesenchymal stem cell properties of hEMSCs and their ability to differentiate into various types of mesenchymal stem cells. The differentiated hEMSCs exhibited morphological features resembling CMs. During the induction period, the number of positive cells for SMAD۶ protein and the expression level of miR-۲۶b-۵p increased and peaking on days ۲۴ and ۳۰, while the expression levels of miR-۱۷-۵p and miR-۳۲-۵p decreased. The Pearson correlation coefficients revealed that SMAD۶ level is inversely correlated with miR-۱۷-۵p and miR-۳۲-۵p and directly correlated with miR-۲۶b-۵p. Conclusion: Our results indicate that miR-۱۷-۵p, miR-۲۶b-۵p, miR-۳۲-۵p, and SMAD۶ are potentially involved in the molecular signaling pathways of transdifferentiation of hEMSCs to CMs.

کلیدواژه ها:

Endometrium-derived mesenchymal stem cells (EMSCs) ، SMAD۶ ، miR-۱۷-۵p ، miR-۲۶b-۵p ، and miR-۳۲-۵p.