Mesenchymal stem cell (MSC) transplantation has shown tremendous promise as a therapy for repair of various tissues of the musculoskeletal, vascular, and central nervous systems. Based on this success, recent research in this field has focused on complex tissue damage, such as that which occurs from traumatic spinal cord injury (TSCI). As the critical event for successful exogenous, MSC therapy is their migration to the injury site, which allows for their anti-inflammatory and morphogenic effects on fracture healing, neuronal regeneration, and functional recover. Thus, there is a need for a cost-effective in vivo model that can faithfully recapitulate the salient features of the injury, therapy, and recovery. To address this, we review the recent advances in exogenous MSC therapy for TSCI and traumatic vertebral fracture repair and the existing challenges regarding their translational applications. We also describe a novel murine model designed to take advantage of multidisciplinary collaborations between musculoskeletal and neuroscience researchers, which is needed to establish an efficacious MSC therapy for TSCI. 1. Introduction With almost 12,000 new spinal cord injuries (SCI) occurring every year in the United States alone, near half a million chronic SCI patients suffer the long term consequences of this devastating injury. Since the major disabilities from SCI are neurological deficits, neural regeneration remains the priority. Consequently, other aspects of SCI, such as vertebral fracture reconstruction, receive less attention. Thus, one major limitation in this field that has contributed to the lack of progress has been the absence of multidisciplinary cooperation between neuroscientists working towards nerve regeneration and orthopaedic investigators working with mesenchymal stem cells (MSCs) for bone repair [1]. One of the most challenging aspects of treating injuries to the spinal cord is the multitude of problems that need to be addressed to restore normal function. These include neural cell death, limited axon regeneration, inflammation and scar formation, and disruption of the neurovascular supply and loss of structural support from the surrounding vertebra. Thus, any therapeutic approach aimed at SCI tissue regeneration requires a coordinated approach in which neural repair is accompanied by fracture repair and revascularization of newly formed tissues [2]. Several types of cell transplants have been proposed for SCI and fracture repair, including stem cells and their differentiated progeny, with the purpose of directly replacing lost
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