Pharmacological activation of mesenchymal stem cells increases gene expression pattern of cell adhesion molecules and fusion with neonatal cardiomyocytes

• Published in: Cell biochemistry and function 2024-07, Vol.42 (5), p.e4090-n/a
• Main Authors: Khan, Irfan, Muneer, Rabbia, Qazi, Rida‐e‐Maria, Salim, Asmat
• Format: Article
• Language: English
• Subjects: Adhesion; Animals; Animals, Newborn; Cardiomyocytes; Cell activation; Cell adhesion; Cell adhesion & migration; Cell Adhesion - drug effects; Cell adhesion molecules; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; cell cycle; Cell Fusion; Cell therapy; Cells, Cultured; Connexins; fusion; Gene expression; Gene fusion; Genes; Homing behavior; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Neonates; Pharmacology; Polymerase chain reaction; rap1 GTP-Binding Proteins - genetics; rap1 GTP-Binding Proteins - metabolism; Rap1 protein; Rats; Regeneration (physiology); RNA-directed DNA polymerase; Stem cell transplantation; Stem cells; Survival; Tissue engineering; Transcription activation; Transplantation; Up-regulation
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.4090

Cellular therapy is considered a better option for the treatment of degenerative disorders. Different cell types are being used for tissue regeneration. Despite extensive research in this field, several issues remain to be addressed concerning cell transplantation. One of these issues is the survival and homing of administered cells in the injured tissue, which depends on the ability of these cells to adhere. To enhance cell adherence and survival, Rap1 GTPase was activated in mesenchymal stem cells (MSCs) as well as in cardiomyocytes (CMs) by using 8‐pCPT‐2′‐O‐Me‐cAMP, and the effect on gene expression dynamics was determined through quantitative reverse transcriptase‐polymerase chain reaction analysis. Pharmacological activation of MSCs and CMs resulted in the upregulation of connexin‐43 and cell adhesion genes, which increased the cell adhesion ability of MSCs and CMs, and increased the fusion of MSCs with neonatal CMs. Treating stem cells with a pharmacological agent that activates Rap1a before transplantation can enhance their fusion with CMs and increase cellular regeneration. Significance Statement Pharmacological activation of mesenchymal stem cells (MSCs) and cardiomyocytes (CMs) resulted in upregulation of cell adhesion genes. This, in turn, increased the cell adhesion ability of MSCs and CMs and promoted the fusion of MSCs with neonatal CMs. Treatment of stem cells before transplantation with a pharmacological agent that leads to Rap1a activation can promote the fusion of MSCs with CMs, leading to increased cellular regeneration.