Mesenchymal Stem Cell Transplantation Reduces Glial Cyst and Improves Functional Outcome After Spinal Cord Compression

Background

Mesenchymal stem cells (MSCs) are multipotent stem cells that have a supportive role in regenerative therapies, especially in the central nervous system, where spontaneous regeneration is limited. MSCs can exert a paracrine activity and modulate the inflammatory response after a central nervous system injury. Spinal cord injury (SCI) leads to permanent neurologic deficits below the injury site, owing to neuronal and axonal damage. Among experimental treatments after SCI, cell transplantation has emerged as a promising approach.

Methods

Using a compression injury model in the mouse spinal cord, MSCs were acutely transplanted into the lesion cavity; injured mice without the graft served as controls. After 26 days, the survival of MSCs was investigated, and their effect on the formation of glial cyst and on injury-related inflammation was evaluated.

Results

Grafted MSCs remained permanently undifferentiated. The lesion volume was reduced by 31.6% compared with control mice despite the fact that astroglial and microglial activation was not altered by the graft. Sensory and motor tests showed that MSC cell therapy results in improvement on a battery of behavioral tests compared with control mice: MSC-treated mice versus control mice scored 0.00 versus 0.50 in the posture test, 0.00 versus 1.50 in the hindlimb flexion test, 3.00 versus 2.25 in the sensory test, and 7.50 mistakes versus 15.83 mistakes in the foot-fault test.

Conclusions

These results underscore the therapeutic potential of MSCs, making them promising treatments for central nervous system pathologies.

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.