Reprogramming autologous skeletal myoblasts to express cardiomyogenic function. Challenges and possible approaches.
Cell transplantation therapy is emerging as a promising mode of treatment following myocardial infarction. Of the various cell types that can potentially be used for transplantation, autologous skeletal myoblasts appear particularly attractive, because this would avoid issues of immunogenicity, tumorigenesis, ethics and donor availability. Additionally, skeletal myoblasts display much higher levels of ischemic tolerance and graft survival compared to other cell types. There is some evidence for improvement in heart function with skeletal myoblast transplantation. However, histological analysis revealed that transplanted myoblasts do not transdifferentiate into functional cardiomyocytes in situ. This is evident by the lack of expression of cardiac-specific antigens, and the absence of intercalated disc formation. Instead, there is differentiation into myotubes that are not electromechanically coupled to neighboring cardiomyocytes. This could in turn limit the clinical efficacy of treatment. This review would therefore examine the various challenges faced in attempting to reprogram autologous skeletal myoblast to express cardiomyogenic function, together with the various possible strategies that could be employed to achieve this objective.
Heng
Boon Chin
BC
Department of Obstetrics and Gynaecology, Faculty of Medicine, National University of Singapore, Singapore.
Haider
Husnain Khawaja
HK
Sim
Eugene Kwang-Wei
EK
Cao
Tong
T
Tong
Guo Qing
GQ
Ng
Soon Chye
SC
D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D032448:Myoblasts, Skeletal / Q000378:metabolism* / Q000637:transplantation*; D032383:Myocytes, Cardiac / Q000502:physiology; D020127:Recovery of Function; D014157:Transcription Factors / Q000502:physiology; D014182:Transplantation, Autologous
D014157:Transcription Factors