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The types of stem cell that can be extracted from accessible fetal tissues such as the umbilical cord and amniotic fluid are somewhat different to both adult stem cells and embryonic stem cells. Ultimately all of these various sources will go away in favor of cell reprogramming on the grounds that pretty much anything other than sourcing cells from a skin or blood sample from the patient in front of you is going to result in excessively costly treatments. It is simply too troublesome to manage the collection and preservation of fetal cells on an industrial scale unless it is the only useful alternative, which is not to mention that they cannot be patient-matched cells in any but the most rare of circumstances.

From a research perspective finding out what these various types of stem cell can achieve in terms of regenerative therapies is a necessary part of the process of guiding advances in cell programming. Embryonic and fetal stem cells provide aiming points and comparisons for cell reprogramming efforts, but that is only helpful if scientists know how to use these cells to produce therapies. Thus even as the production of induced pluripotent stem cells from ordinary skin cells is moving ahead, the first clinical trials are beginning, and researchers are becoming ever better at producing stem cells that are increasingly like those seen in various stages of embryonic development, it is still the case that various research groups are exploring what can be done with fetal and embryonic stem cells.

Here is an interesting review that notes fetal stem cells work in muscle regeneration in much the same way as other stem cell treatments have been shown to produce effects: they are not acting directly to restore tissue, but rather changing the signaling environment to alter the behavior of native cells. At some point the cell part of many cell therapies will fall away in favor of directly manipulating cell signaling, but there is still much to be discovered about which signals are needed and how to deliver them in a way that mimics the presence of stem cells.

Fetal stem cells and skeletal muscle regeneration: a therapeutic approach

More than 40% of the body mass is represented by muscle tissue, which possesses the innate ability to regenerate after damage through the activation of muscle-specific stem cells, namely satellite cells. Muscle diseases, in particular chronic degenerative states of skeletal muscle such as dystrophies, lead to a perturbation of the regenerative process, which causes the premature exhaustion of satellite cell reservoir due to continuous cycles of degeneration/regeneration. Nowadays, the research is focused on different therapeutic approaches, ranging from gene and cell to pharmacological therapy, but still there is no definitive cure in particular for genetic muscle disease. Keeping this in mind, in this article, we will give special consideration to muscle diseases and the use of fetal derived stem cells as a new approach for therapy. Cells of fetal origin, from cord blood to placenta and amniotic fluid, can be easily obtained without ethical concern, expanded and differentiated in culture, and possess immune-modulatory properties. The in vivo approach in animal models can be helpful to study the mechanism underneath the operating principle of the stem cell reservoir, namely the niche, which holds great potential to understand the onset of muscle pathologies.

Muscle pathologies are devastating diseases and nowadays researchers still make efforts to find a cure and not a therapy alone. It has been demonstrated that, after injection in injured or diseased muscle, fetal stem cells act through a mechanism that is mostly due to a bystander effect rather than a direct differentiation. The indirect action is mainly supposed to enhance the production of cytokines, such as VEGF, that stimulate the temporary restoring of the tissue function. To obtain a long lasting action due to efficient cell integration and tissue repopulation, fetal stem cells need to be genetically modified, forcing their differentiation in tissue-specific cells. Nevertheless, the development of safe genetic manipulation methods could make cells of fetal origin appealing for therapeutic application.

Conversely, the long-term positive effect observed using freshly isolated murine amniotic fluid stem (AFS) cells, highlights that they could have a decisive role in replenishing the muscle stem cell niche, which represent the reservoir of cells able to rescue the defect. Indeed, AFS cells are a safe and immune-privileged cell source prone to integrate in muscle tissue. This knowledge opens the challenge to improve the culture protocol for the AFS cells of human origin, which, so far, is still a limit to overcome for future clinical application to treat genetic and non-genetic muscle dysfunctions (dystrophies, skeletal muscle malformations, traumatic injuries).