Abstract
The skeletal muscle is considered to be an ideal target for stem cell therapy as it has an inherent regenerative capacity. Upon injury, the satellite cells, muscle stem cells that reside under the basal lamina of the myofibres, start to differentiate in order to reconstitute the myofibres while maintaining the initial stem cell pool. In recent years, it has become more and more evident that epigenetic mechanisms such as histon modifications, DNA methylations and microRNA modulations play a pivatol role in this differentiation process. By understanding the mechanisms behind myogenesis, researchers are able to use this knowledge to enhance the differentiation and engraftment potential of different muscle stem cells. Besides manipulation on an epigenetic level, recent advances in the field of genome-engineering allow site-specific modifications in the genome of these stem cells. Combining epigenetic control of the stem cell fate with the ability to site-specifically correct mutations or add genes for further cell control, can increase the use of stem cells as treatment of muscular dystrophies drastically. In this review, we will discuss the advances that have been made in genome-engineering and the epigenetic regulation of muscle stem cells and how this knowledge can help to get stem cell therapy to its full potential.
Highlights
The skeletal muscle accounts for ~40% of the human body weight and is important for movement and stability
In the case of valproic acid, this epigenetic reprogramming was even strong enough to induce myocyte differentiation from PSCs without the need for prior mesoderm formation or to directly transdifferentiate fibroblast and adipose-derived stem cells [65,66,67]. These findings indicate that these molecules can boost the myogenic potential of several sorts of stem cells in order to increase their in vivo efficacy.it should be noted that in adult stem cells, the effect of HDACi is stage-specific
We examined the convergence of genetics and epigenetics that act in concert to advance our knowledge on myogenic stem cells and accelerate the development of novel therapies
Summary
The skeletal muscle accounts for ~40% of the human body weight and is important for movement and stability. Despite preclinical results, or clinical responsible for muscle regeneration in a physiological setting They have the inherent capacity to reconstitute the muscle fibres, these stem cells lose their engraftment potential rapidly when they are cultured ex vivo. These cells lack migratory capacity causing the need for high-density cell injections at multiple sites to reach significant engraftment [10,11]. Another inherent stem cell is the mesoangioblast (MAB), a vessel-associated stem cell that can differentiate into all tissues of mesodermal origin [12]. Researchers are still struggling to obtain a pure myogenic population from iPSCs in order to avoid the risk of uncontrolled cell growth, once injected in vivo
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