Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

The central nervous system (CNS) is known to have a limited regenerative capacity, making the path toward the development of effective therapeutic strategies challenging. Neuroregeneration and neural tissue engineering are highly diverse, relatively new biomedical fields that have the potential to target the cause of CNS conditions, and not only symptoms like currently used conventional clinical treatments. Experimental studies in animals such as mice have demonstrated curative techniques for severe and intractable CNS disorders such as stroke and SCI. However, we fail to cure humans when the therapies reach randomized clinical trials, suggesting that something is problematic with the translation pipeline.

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  Stem cell-derived exosomes have been found to promote tissue repair and regeneration, while it is believed that exosome inclusions induce epigenetic changes in the recipient’s cells, positively regulating their fates by promoting proliferation or inhibiting apoptosis.
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  An ideal hydrogel for CNS regeneration requires the following: 1) in situ gelling at the CNS lesion site to achieve an accurate fit with irregularly shaped tissue defects; 2) effective retention and stabilization of any bioactive molecules, cells or exosomes used, to avoid rapid clearance and reactions caused by non-targeted treatment applications.
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  Rodents, nonhuman primates and humans demonstrate crucial differences in qualities such as size, neuroanatomy, behavior, and pathophysiology. This raises the question of how these differences impact the restorative effect of a tested treatment, the functional impact on the subject after an intervention, the maintenance of desired results, and the emergence of adverse effects as well as their severity.