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

Neuroscience Institute Cavalieri Ottolenghi, Neuroscience Institute of Turin, University of Turin, Italy. Electronic address: .
World Neurosurgery (Impact Factor: 2.88). 09/2012; 81(1). DOI: 10.1016/j.wneu.2012.08.014
Source: PubMed


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.

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.

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.

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

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    • "Therefore, progenitor OECs have been proposed as one of the most promising cell sources for SCI therapy. BMSCs have been shown to be able to promote functional recovery [11] [12], by intrathecal injection or intravenous perfusion. The mechanisms underlying the beneficial effects of BMSCs transplants may include neuroprotection by secreting or inducing the expression of neuroprotective molecules in the injured tissues [12], contribution to a permissive environment for axonal regeneration and neural tissue reconstruction [13], acceleration of the tissue repair process [9], and modulation of the neuroinflammatory response. "
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    ABSTRACT: The mechanisms behind the repairing effects of the cotransplantation of olfactory ensheathing cells (OECs) with bone marrow mesenchymal stromal cells (BMSCs) have not been fully understood. Therefore, we investigated the effects of the cotransplantation of OECs with BMSCs on antiapoptotic effects in adult rats for which the models of SCI are induced. We examined the changes in body weight, histopathological changes, apoptosis, and the expressions of apoptosis-related proteins after 14 days and 28 days after transplantation. We also assessed animal locomotion using BBB test. We found that treatment with OECs and BMSCs had a remissive effect on behavioral outcome and histopathological changes induced SCI. Furthermore, we observed the significant antiapoptotic effect on cotransplant treated group. In addition, cotransplantation of OECs with BMSCs was found to have more significant repairing effect than that of OECs or BMSCs alone. Furthermore, the recovery of hind limb could be related to antiapoptotic effect of OECs and BMSCs through downregulating the apoptotic pathways. Finally, our data suggested the cotransplantation of OECs with BMSCs holds promise for a potential cure after SCI through the ability to incorporate into the spinal cord.
    Full-text · Article · Aug 2015 · Stem cell International
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    ABSTRACT: Nearly 1.5 million people in the US live with a spinal cord injury (SCI). The cost to the health system is estimated at over $10billion annually likely because over 65% of SCIs occur at the cervical level. Despite medical advances, many SCI patients still experience substantial neurological disability and high dependency with severe loss of motor, sensory and autonomic function. The consensus from a combination of in vitro studies and in vivo models is that mesenchymal or stromal cells, and possibly even neural progenitors, regardless of derivation act through the provision of trophic support and inflammatory modulation. Indeed, they have been found to secrete a wide spectrum of diffusible factors with known roles in both. As such, mesenchymal cells, obtainable from multiple tissues, are ideally suited to addressing many pathophysiological consequences of SCI. Advances in understanding the latter, structural and functional magnetic resonance imaging, image-guided microneurosurgical techniques and transplantable cell biology have enabled the clinical use of cell-based therapies. Of the twenty most recent cell therapy clinical trials for SCI, seven involve adult bone marrow mesenchymal cells and six others umbilical cord cells. This reflects the growing recognition of the clinical potential of perinatal cells. However, a limited understanding of how best to exploit the capabilities of these cells impedes a full-scale clinical deployment. This mini-review focuses on recent developments that are likely to facilitate the targeted application of these cells to treat specific secondary pathophysiological processes.
    Full-text · Article · Dec 2012 · Current Stem Cell Research & Therapy
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    ABSTRACT: Cell transplantation, as a therapeutic intervention for spinal cord injury (SCI), has been extensively studied by researchers in recent years. A number of different kinds of stem cells, neural progenitors, and glial cells have been tested in basic research, and most have been excluded from clinical studies because of a variety of reasons, including safety and efficacy. The signaling pathways, protein interactions, cellular behavior, and the differentiated fates of experimental cells have been studied in vitro in detail. Furthermore, the survival, proliferation, differentiation, and effects on promoting functional recovery of transplanted cells have also been examined in different animal SCI models. However, despite significant progress, a “bench to bedside” gap still exists. In this paper, we comprehensively cover publications in the field from the last years. The most commonly utilized cell lineages were covered in this paper and specific areas covered include survival of grafted cells, axonal regeneration and remyelination, sensory and motor functional recovery, and electrophysiological improvements. Finally we also review the literature on the in vivo tracking techniques for transplanted cells.
    Full-text · Article · Jan 2013
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