Reviewing the Development of Stem Cell Treatments for Muscle Wasting and Retinal Degeneration

Below you'll find links to open access reviews on the current state of two different areas of applied stem cell science: reversing muscle loss in aging and degenerative conditions, and repairing forms of blindness caused by retinal degeneration. Consider these representative of many other similar efforts, as for near every part of the body there are teams out there somewhere working on how to apply stem cells to reverse damage and restore function. It is a very broad, active, and well-funded field of research, all told.

Retinal Stem Cells and Regeneration of Vision System

Eye formation requires the coordination of complex interactions from multiple cellular sources to create the cell behaviors that progressively shape the developing eye. The mechanisms of development and differentiation of eye are remarkably similar in all vertebrates. During retinogenesis, proliferating retinal pigment cells (RPCs) and newly generated cells are confined at the peripheral margin of the retina. In fish and amphibians, this region is maintained after embryonic development and this specialized region referred to as the CMZ. The retina of many fish and amphibians continue to grow throughout their life. The increase in retinal size is due to in part to the addition of new neurons, at the CMZ. In birds, neurogenesis at the CMZ decreases dramatically than that observed in fish and amphibians. Furthermore, in rodents the retinal margin does not exhibit mitotic activities after the first week of postnatal life. It is interesting to note that there might be a direct correlation of the evolutionary importance of the ability of retina to regenerate with the presence of RPCs and their potential to generate retinal neurons.

Adult mammalian retina has long been known to be devoid of stem cells and has lost the ability to regenerate after damage. Nevertheless, several groups have reported that pigmented cells isolated from the adult human ciliary epithelium can transdifferentiate to retinal progenitor-like cells and Müller glia cells can display characteristics of neural progenitor cells, thus identified both cell populations as potential candidate for stem-cell based therapies to regenerate visual function.

It seems logical that it is preferable to mobilize endogenous RPCs to drive the repair process in the retina. However, the challenge of using endogenous RPCs for self repair will be to identify appropriate cellular sources and molecules, including pharmacological agents, that can expand the endogenous cell pool and reactivate the regenerative processes similar to those described for the lower vertebrates in the mammalian retina.

Recent advances in stem cell research have raised the possibility to use human embryonic stem cells and induced pluripotent stem cells to repair or regenerate damaged mammalian retina. Cell transplantation is the most direct approach towards replacing damaged retinal cells and restoration of lost visual function. To achieve a breakthrough in cell replacement therapies in retinal degenerative diseases would require isolation and molecular characterization of human RPCs for specific neuronal replacement in the actively degenerating adult retina and that these new cells survive without immune suppression as well as displaying evidence of integration into host circuitry.

Advancements in stem cells treatment of skeletal muscle wasting

Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders, in which progressive muscle wasting and weakness is often associated with exhaustion of muscle regeneration potential. Although physiological properties of skeletal muscle tissue are now well known, no treatments are effective for these diseases. Muscle regeneration was attempted by means of transplantation of myogenic cells (from myoblast to embryonic stem cells) and also by interfering with the malignant processes that originate in pathological tissues, such as uncontrolled fibrosis and inflammation. Taking into account the advances in the isolation of new subpopulation of stem cells and in the creation of artificial stem cell niches, we discuss how these emerging technologies offer great promises for therapeutic approaches to muscle diseases and muscle wasting associated with aging.

New approaches using organisms genetically modified and transgenic mouse models proposed the importance of the microenvironment - like the niche and the extrinsic factors - to be a key component in stem cell regulation. Particularly, significant progress has been made in understanding how satellite cells can act as tissue-specific adult stem cells in skeletal muscle. In the same time, many studies investigated the satellite cell properties in term of efficacy after in vivo transplantation using novel approaches such as non-invasive bioluminescence imaging. These tools provided information for assessing not only satellite cell function but, in general, stem cell function. Investigations on the molecular nature of stem cell niche signals on in vivo models and short-term cultures of isolated myofibers, are now on-going.

Bioengineering offers significant tools for the development of strategies to mimic biochemical and biophysical features of the in vivo niche microenvironment. We hope that the synthesis of biomaterials, micro-fabrication technology and stem cell biology will provide systems potentially innovative to better understand how stem cell fate is controlled. Development of biomaterials able to re-create an in vitro stem cell niche could give rise to novel insights into understanding the molecular cues, critical for the in vitro maintenance and expansion of muscle stem cells. Above all, these in vitro systems can well lead to the generation of adequate numbers of stem cells and the ability to control their differentiation in order to maximize their utility, not only as cell-based therapeutics for tissue regeneration and replacement, but also as the control of inflammation after muscle damage.


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