The role of cell cycle in reprogramming toward induced pluripotent stem cells (iPSCs)

2022 ◽  
pp. 147-194
Author(s):  
Irina Neganova
2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Wuqiang Zhu ◽  
Meng Zhao ◽  
Saidulu Mattapally ◽  
Ling Gao ◽  
Jianyi Zhang

Transplantation of cardiomyocytes derived from induced pluripotent stem cells (iPSCs) improves cardiac function in animal models with myocardial infarction. However, the poor number of survived cells and the low proliferation capability of cardiomyocyte derived from iPSCs are bottlenecks in myocardial repair with cell therapy. We hypothesize that increasing the number of surviving iPSC-CMs in the engraftment via cell cycle induction may lead to a transmural replacement of scar tissue and a lasting restoration of cardiac function. Cyclin D2 is a protein that regulates cell cycle transition from G1 to S phase. We transfected MHC-cyclin D2 (designated as MHC-cycD2) cDNA into the iPSCs, and differentiated the iPSCs into cardiomyocytes. Comparing to non-expressing cells, MHC-cycD2-expressing cardiomyocytes displayed increased Brdu incorporation activity, suggesting the enhanced cell cycle in MHC-cycD2-expressing cardiomyocytes. Cell cycle activity was confirmed by increased number of Ki-67 and PCNA positive immunostaining cardiomyocytes and more contractile embryonic body cell mass in MHC-cycD2-expressing culture compared to non-expressing culture. Data from Q-PCR and histology suggested that expression of MHC-cycD2 didn’t alter the pluripotency or cardiomyogenic potential of iPSCs. Thus, we have successfully induced cell cycle in iPSC-derived cardiomyocytes via expression of cyclin D2. We are currently studying if MHC-cycD2-expressing iPSC-cardiomyocytes exhibit superior regenerative potential compared to their non-expressing counterparts following transplantation into chronically infarcted hearts.


2015 ◽  
Vol 21 (7-8) ◽  
pp. 1261-1274 ◽  
Author(s):  
Brian O. Diekman ◽  
Pratiksha I. Thakore ◽  
Shannon K. O'Connor ◽  
Vincent P. Willard ◽  
Jonathan M. Brunger ◽  
...  

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