Transplantation of satellite stem cells, which are found in skeletal muscles, might potentially treat degenerative muscle diseases such as Duchenne muscular dystrophy. However, muscle satellite cells have an unfortunate tendency to lose their ability to be transplanted then they are grown in culture.
In order to generate enough cells for transplantation, the cells are isolated from the body and then they must be grown in culture. However, in order to properly grow in culture, the cells must be prevented from differentiating because fully differentiated cells stop growing and die soon after transplantation. Several growth factors, cytokines, and chemicals have been used in muscle satellite cell culture systems. Unfortunately, the optimal culture conditions required to maintain the undifferentiated state, inhibit differentiation, and enhance eventual transplantation efficiency have not yet been established satisfactorily.
Because it is impossible to extract enough satellite cells for therapeutic purposed from biopsies, these cells must be expanded in culture. However this very act of culturing satellite cells renders them inefficient for clinical purposes. How can we break away from this clinical catch-22?
Shin’ichi Takeda from the National Center of Neurology and Psychiatry and his colleagues have used growth factors to maintain muscle satellite cell efficiency during cell culture. In particular, Takeda and others used a growth factor called leukemia inhibitory factor (LIF). LIF effectively maintains the undifferentiated state of the satellite cells and enhances their expansion and transplantation efficiency. LIF is also thought to be involved in muscle regeneration.
This is the first study on the effect of LIF on the transplantation efficiency of primary satellite cells,” said Shin’ichi Takeda of the National Center of Neurology and Psychiatry. “This research enables us to get one step closer to the optimal culture conditions for muscle stem cells.”
The precise mechanisms by which LIF enhances transplantation efficiency remain unknown. Present work is trying to determine the downstream targets of LIF. Identifying the precise mechanisms by which LIF enhances satellite cell transplantation efficiency would help to clarify the functional importance of LIF in muscle regeneration, and, even more importantly, further its potential application in cell transplantation therapy.
The reference for this paper is: N. Ito et al., “Enhancement of Satellite Cell Transplantation Efficiency by Leukemia Inhibitory Factor,” Journal of Neuromuscular Diseases, 2016; 3 (2): 201. DOI: 10.3233/JND-160156.