• Nanion技术: 离子通道研究的智能工具

    Nanion技术: 离子通道研究的智能工具

  • SyncroPatch 384: HTS Automated Patch Clamp

    SyncroPatch 384: HTS Automated Patch Clamp

  • SURFE²R 96SE: 非标记高通量转运体筛选

    SURFE²R 96SE: 非标记高通量转运体筛选

  • Dynamic Clamp: Patchliner

    Dynamic Clamp: Patchliner

  • 脂双层记录: Orbit产品系列

    脂双层记录: Orbit产品系列

  • CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

    CardioExcyte 96 SOL:用光遗传的手段起搏心肌细胞

我们的产品目录

SyncroPatch 384

SyncroPatch 384

Patchliner

Patchliner

Port-a-Patch

Port-a-Patch

Port-a-Patch mini

Port-a-Patch mini

CardioExcyte 96

CardioExcyte 96

FLEXcyte 96

FLEXcyte 96

SURFE²R 96SE

SURFE²R 96SE

SURFE²R N1

SURFE²R N1

Orbit 16 TC

Orbit 16 TC

Orbit Mini

Orbit Mini

Vesicle Prep Pro

Vesicle Prep Pro

Buffer Solution

Buffer Solution

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

icon sp96 CardioExcyte 96 prepublication in Research Square (2021)

Authors:
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.

Journal:

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


Abstract: 

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.

返回总览

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.