SUMMARY
Researchers from the Department of Bioengineering at UCLA have identified key players in in both preventing and boosting cardiac reprogramming. This innovation can be used for in vivo human cardiac reprogramming to provide a novel approach for cardiac regeneration in the clinic and other fields of regenerative medicine.
BACKGROUND
Ischemic heart disease is a leading cause of global mortality, accounting for over 9 million deaths per year according to the World Health Organization. A variety of stem cell therapies have been explored including adult mesenchymal stem cells and cardiomyocytes derived from pluripotent stem cells. However, preclinical and clinical trials have not resulted in any effective therapies due to extensive cell death after transplantation, lack of integration of transplanted cardiomyocytes, and detrimental ventricular remodeling.
The advancement of cell reprogramming opens a new avenue to convert differentiated cells into induced pluripotent stem cells and other cells such as cardiomyocytes. This has a tremendous potential for regenerative medicine and disease modeling. Direct cardiac reprogramming can convert fibroblasts into induced cardiomyocytes in vitro and potentially translated in vivo by the local delivery of GMT encoding retroviruses to improve heart function and regeneration. Interestingly, it was observed that in vivo reprogramming cardiomyocytes were more efficient and mature than in vitro reprogramming, possible due to the local micro-environment. However, the underlying mechanisms are not clear, and the reprogramming efficiency needs further improvement for effective regenerative therapy.
INNOVATION
Dr. Song Li and his team at UCLA discovered that immune cells play important roles in preventing and boosting cardiac reprogramming. By recognizing critical cytokines that modulate cardiac reprogramming, the inventors discovered how to modulate immune polarization with steroidal anti-inflammatory drugs, nonsteroidal anti-inflammatory drugs and statin drugs to enhance cardiac reprogramming efficiency.
APPLICATIONS
ADVANTAGES
State of Development: The description of the present invention will be submitted for publication to Nature Biomedical Engineering.
Related Papers (from the inventors only): Pending