Mesenchymal Stem Cell Transplantation Reduces Glial Cyst and Improves Functional Outcome After Spinal Cord Compression
ABSTRACT OBJECTIVE: Mesenchymal stem cells (MSCs) are multipotent stem cells that play a supportive role in regenerative therapies, especially in the CNS where spontaneous regeneration is limited. MSCs can exert a paracrine activity and modulate the inflammatory response after a CNS injury, Spinal cord injury (SCI) leads to permanent neurological deficits below the injury site, due to neuronal and axonal damage. Among the experimental treatments following SCI, cell transplantation emerged as a promising approach. METHODS: We used a compression injury model in the mouse spinal cord and we acutely transplanted MSCs into the lesion cavity; injured mice without the graft served as controls. After 26 days we investigated the survival of MSCs and evaluated their effect on the formation of the glial cyst and on injury-related inflammation. RESULTS: Grafted MSCs remained permanently undifferentiated. In MSC-treated mice the lesion volume was reduced by 31.6%, compared to control mice, despite astroglial and microglial activation was not altered by graft. Moreover sensory and motor tests demonstrated that MSC cell therapy results in improvement on a battery of behavioural tests, in comparison to control mice: in detail, MSC-treated mice vs control ones respectively registered the score 0.00 vs 0.50 in the posture test, 0.00 vs 1.50 in the hindlimb flexion test, 3.00 vs 2.25 in the sensory test, and finally 7.50 mistakes vs 15.83, respectively, in the foot-fault test. CONCLUSION: Our results underscore the therapeutic potential of MSCs, making them promising candidates for CNS pathologies.
SourceAvailable from: Vikram Sabapathy
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ABSTRACT: Spinal cord injury (SCI) is a devastating trauma causing long-lasting disability. Although advances have occurred in the last decade in the medical, surgical and rehabilitative treatments of SCI, the therapeutic approaches are still not ideal. The use of cell transplantation as a therapeutic strategy for the treatment of SCI is promising, particularly since it can target cell replacement, neuroprotection and regeneration. Cell therapies for treating SCI are limited due to several translational roadblocks, including ethical and practical concerns regarding cell sources. The use of iPSCs has been particularly attractive, since they avoid the ethical and moral concerns that surround other stem cells. Furthermore, various cell types with potential for application in the treatment of SCI can be created from autologous sources using iPSCs. For applications in SCI, the iPSCs can be differentiated into neural precursor cells, neurons, oligodendrocytes, astrocytes, neural crest cells and mesenchymal stromal cells that can act by replacing lost cells or providing environmental support. Some methods, such as direct reprogramming, are being investigated to reduce tumorigenicity and improve reprogramming efficiencies, which have been some of the issues surrounding the use of iPSCs clinically to date. Recently, iPSCs have entered clinical trials for use in age-related macular degeneration, further supporting their promise for translation in other conditions, including SCI.