Mesenchymal Stem Cell Therapy Aids Spinal Cord Regeneration in Rats

Arguably the most reliable of first generation stem cell therapies is the transplantation of mesenchymal stem cells. The cells don't last long in the recipient, which is a problem characteristic of all such cell therapies, but the signals they secrete while still alive act to change native cell behavior and suppress inflammation for an extended period of time. Since chronic inflammation degrades tissue maintenance and regeneration, this respite can allow some degree of healing that wouldn't have otherwise occurred - though that benefit is much less reliable than the initial suppression of inflammation.

In the study reported here, researchers turn this set of mechanisms towards regeneration from spinal injury, demonstrating improvements in rats. This is still a long way from comprehensive repair, and much of the discussion centers around just how variable and poorly controlled the cell behavior is in this "most reliable" of cell therapies, but it is a good deal better than failing to intervene in the inflammation that causes scarring following nerve injury. Nerves are in principle capable of regeneration in absence of that scar formation: the mechanisms to support that regeneration exist in mammals, but are not deployed at the right time and in the right way. One line item is the behavior of macrophages, an important player in the intricate dance of cell types involved in regeneration, and whether they adopt the beneficial M2 polarization or the inflammatory M1 polarization. This topic shows up in a lot of regenerative research these days.

There are numerous studies of the therapeutic potential of combinatorial approaches based on mesenchymal stem cell (MSC) therapy and biomaterials for spinal cord injury (SCI) treatment. The transplantation of bone marrow-MSCs combined with a gelatin matrix into the area of complete rat spinal cord transection in the subacute period improves inflammation, stimulates angiogenesis, reduces abnormal cavitation and promotes regeneration of nerve fibers. Human umbilical cord blood-derived MSCs combined with hydrogel implanted into the area of injury can significantly modify the immune response in a proinflammatory environment within the area of SCI by increasing the macrophage M2 population and promoting an appropriate microenvironment for regeneration.

We have studied the effects of the application of adipose-derived mesenchymal stem cells (AD-MSCs) combined with a fibrin matrix on structural and functional recovery following SCI in a subacute period in rats. Our results demonstrated that the AD-MSC application is found to exert a positive impact on the functional and structural recovery after SCI that has been confirmed by the behavioral/electrophysiological and morphometric studies demonstrating reduced area of abnormal cavities and enhanced tissue retention in the site of injury.

We have also assessed astroglial and microglial cells in this study. The results obtained confirm the evidence that AD-MSCs are able to prevent the second phase of neuronal injury by contributing to astroglia and microglia suppression. The latter is consistent with past results, which showed that intravenous injection of AD-MSCs after acute SCI in dogs may prevent further damage through enhancement of antioxidative and anti-inflammatory mechanisms including through lesser microglial infiltration in injured tissue.

Considering their unique therapeutic properties, their ease of accessibility and expansion, AD-MSCs combined with a scaffold reveals a potential for a widespread use in clinical medicine. Nevertheless, there remain critical challenges - (1) standardization of generation protocols, including cell culture conditions, (2) the heterogeneity of secretory phenotype of the MSC population, (3) cellular mechanisms and biological properties of MSCs should be disclosed more clearly, (4) translation to the clinic will need preclinical studies on larger animals, (5) randomized, controlled, multicenter clinical trials are necessary to determine the optimal conditions and doses for MSC therapy.

Link: https://doi.org/10.3389/fphar.2018.00343

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