Peer-Review ReportMesenchymal Stem Cell Transplantation Reduces Glial Cyst and Improves Functional Outcome After Spinal Cord Compression
Introduction
Mesenchymal stem cells (MSCs) are self-renewing, multipotent stem cells that can differentiate into several types of mesenchymal tissues (33). MSCs have an important supportive role in regenerative therapies, particularly in the central nervous system (where spontaneous regeneration is very limited), supporting axonal growth and the maintenance of synaptic connections and preventing neuronal death by reducing apoptosis and limiting free radical generation (17). MSCs also secrete cytokines and growth factors, exerting a paracrine influence on damaged tissues 5, 11. Finally, MSCs can interact with the host immune system, modulating the inflammatory response to insult 15, 29.
Spinal cord injury (SCI) affects approximately 6 million people worldwide with profound effects on the quality of life and life expectancy of SCI victims, most of whom are relatively young 25, 37. Traumatic SCI leads to hemorrhage, ischemia, edema, a strong inflammatory response, reactive gliosis, the formation of glial scars and cystic cavities, and loss of neurons and glia; it is often accompanied by severe neurologic dysfunction and disability 8, 25.
Stem cells hold great promise for treating SCI. In an earlier publication, we showed the benefits of using MSCs in a lesion model that involved spinal cord hemisection (3). In this article, we explore the potential benefits of using MSCs in a murine compression SCI model; the focus of our analysis is on how MSCs alter the inflammatory response and the formation of glial cyst and on how these changes influence functional recovery. To our knowledge, this is the first report to employ undifferentiated MSCs in an acute SCI model and to document lesion volume reduction and behavioral improvement.
Section snippets
Experimental Animals
We used 2-month-old C57BL/6J male mice (Harlan-Italy, San Pietro al Natisone, Italy) to produce the SCI model. Animals had free access to food and water. All experimental procedures on live animals were performed according to the European Communities’ Council Directive of 24 November 1986 (86/609/EEC) and University of Torino’s institutional guidelines for animal welfare (DL 116/92); efforts were made to minimize the number of animals used and their suffering. BCF1 mice, which express enhanced
Results
Neuronal survival, inflammation, and lesion size were analyzed and compared between transplanted and control groups.
Discussion
Having already obtained positive results with the use of MSC transplants in a hemisection model, we evaluated MSC transplantation as a possible therapeutic approach in the spinal cord compression model.
Conclusions
Our study shows that early transplantation of MSCs into the compressed spinal cord reduces glial cyst, resulting in neuroprotection and consequently supporting functional recovery after injury. These findings support our positive results with use of MSC grafts in a mouse SCI model, where they promote the sprouting of raphespinal axons caudal to the lesion (3). Such preclinical results identify MSCs as strong candidates for cell transplantation therapy after SCI to limit the histologic and
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Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.