Triiodo-L-Thyronine Promotes the Maturation of Cardiomyocytes Derived From Rat Bone Marrow Mesenchymal Stem Cells

Abstract

Bone marrow mesenchymal stem cells (BMMSCs) can differentiate into cardiomyocytes and be used in cardiac tissue engineering for heart regeneration. However, the effective clinical application of cardiomyocytes derived from BMMSCs is limited because of their immature phenotype. The aim of this study was to investigate the potential of triiodo-L-thyronine (T3) to drive cardiomyocytes derived from BMMSCs to a more mature state. BMMSCs were divided into 3 groups: untreated controls, differentiated, and T3 treated. The differentiation potential was evaluated by immunofluorescence microscopy and flow cytometry. Data were represented as the numbers of cells positive for the troponin I (cTnI), α-actinin, GATA4, and the connexin-43 (Cx-43). The mRNA levels of these specific markers of cardiomyocytes were determined by quantitative real-time polymerase chain reaction. The levels of cardiomyocytes markers protein and octamer-binding transcription factor 4 (Oct-4) were determined by Western blot analyses. Our data demonstrate that T3 treatment leads to a significant increase in cells positive for cTnI, GATA4, Cx-43, and α-actinin. The mRNA and protein expression levels of these specific markers of cardiomyocytes were also increased after T3 treatment. At the same time, the protein expression level of Oct-4 was substantially downregulated in T3-treated cells. These results demonstrate that T3 treatment increases the differentiation of BMMSCs induced to cardiomyocytes and promotes their maturation.

Ticagrelor Improves Remodeling, Reduces Apoptosis, Inflammation and Fibrosis and Increases the Number of Progenitor Stem Cells After Myocardial Infarction in a Rat Model of Ischemia Reperfusion

“…Octamer-binding transcription factor 4 (Oct4) mediates pluripotency in embryonic stem cells and mesenchymal stem cells [45]. Cardiac differentiation of bone marrow stem cells was associated with downregulation of Oct4 expression [46,47]. Thus, the increase in Oct4 signifies recruitment of pluripotent stem cells.…”

Substrate Stiffness, Cell Anisotropy, and Cell–Cell Contact Contribute to Enhanced Structural and Calcium Handling Properties of Human Embryonic Stem Cell-Derived Cardiomyocytes

“…Previous studies with immature cardiomyocytes have shown enhanced maturation using several different methods. Prolonged cell culture is one of the most common techniques, which involves allowing the cells to grow in culture for an extended period of time. − Alternatively, cell biophysical pathways can be activated via cues such as cell anisotropy, − cell–cell contact, , substrate stiffness, − applied mechanical strain, − or electrical pacing. − Pharmacological and viral biochemical agents have also been found to enhance the maturation of immature cardiomyocytes. − While many of these developmental cues have been investigated, it would be beneficial to clarify the impact of these individual stimuli, or combinations of these stimuli, on hPSC-CM structure and function.…”

Small molecule-mediated rapid maturation of human induced pluripotent stem cell-derived cardiomyocytes

“…Hence, we selected two small molecules-asiatic acid (AA) and GW501516-to specifically activate the PPAR/PGC-1α pathway in iPSC-CMs. T3 is a hormone involved in cardiac development, well known for its effect on iPSC-CMs maturation and has been shown to stimulate mitochondrial respiratory capacity and biogenesis, by activating p43, an activator of mitochondrial genome replication [11,[25][26][27]. In this study, T3 was used as a positive control due to its known increased respiratory capacity and electrophysiological maturation in iPSC-CMs, though the mechanism has not been established yet [28] (Fig.…”