• CE Slide 1
  • CE Slide 2
  • CE slide 3
  • CE slide 4
  • CardioExcyte 96

    Combined impedance and MEA-like recordings
  • CardioExcyte 96

    For cardiac safety screening
  • CardioExcyte 96

    Next generation label-free cell analysis
  • CardioExcyte 96

    Intuitive data analysis & arrhythmia detection

2021 - Transient Cell Cycle Induction in Cardiomyocytes to Treat Ischemic Heart Failure

icon sp96 CardioExcyte 96 prepublication in Research Square (2021)

Abouleisa R., Ou Q., Tang X-L., Solanki M., Guo Y., Nong Y., Mcnally L., Lorkiewicz P., Kassem K., Ahern B., Choudhary K., Thomas R., Huang Y., Juhardeen H., Siddique A., Ifthikar Z., Salama A-B., Hammad S., Elbaz A., Ivey K., Satin J., Hill B., Srivastava D., Bolli R., Mohamed T.


Research Square (2021) doi: 10.21203/rs.3.rs-122026/v1


The regenerative capacity of the heart after myocardial infarction (MI) is limited. Our previous study showed that ectopic introduction of Cdk1/CyclinB1 and Cdk4/CyclinD1 complexes (4F) promotes cardiomyocyte proliferation in 15-20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after MI. Here, we aim to identify the necessary reprogramming stages during the forced cardiomyocyte proliferation with 4F on a single cell basis. Also, we aim to start the first preclinical testing to introduce 4F gene therapy as a candidate for the treatment of ischemia-induced heart failure. Temporal bulk and single-cell RNAseq and further biochemical validations of mature hiPS-CMs treated with either LacZ or 4F adenoviruses revealed full cell cycle reprogramming in 15% of the cardiomyocyte population after 48 h post-infection with 4F, which was associated with sarcomere disassembly and metabolic reprogramming. Transient overexpression of 4F, specifically in cardiomyocytes, was achieved using a polycistronic non-integrating lentivirus (NIL) encoding the 4F; each is driven by a TNNT2 promoter (TNNT2-4F-NIL). TNNT2-4F-NIL or control virus was injected intramyocardially one week after MI in rats or pigs. TNNT2-4F-NIL treated animals showed significant improvement in left ventricular ejection fraction and scar size compared with the control virus treated animals four weeks post-injection.

In conclusion, the present study provides a mechanistic demonstration of the process of forced cardiomyocyte proliferation and advances the clinical feasibility of this approach by minimizing the oncogenic potential of the cell cycle factors using a novel transient and cardiomyocyte-specific viral construct.

Download here.

Back to Overview

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.