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A Placental Stem Cell Derived Treatment for Acquired Spinal Cord Injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Spinal cord injury (SCI) results in functional impairments ranging from sensory and motor deficits to irreversible paralysis. Approximately 1.4 million people in the United States suffer from some form of SCI and associated healthcare costs can exceed 4.5 million dollars per patient. Spina bifida (SB) is a congenital form of SCI and is the most common cause of congenital paralysis. Using placental mesenchymal stromal cells (PMSCs), we have developed a new treatment for SB. Our preclinical results indicate that PMSCs dramatically and consistently cure hindlimb paralysis in a well-established fetal lamb model. Given the success of the congenital model of SCI, we hypothesize that PMSCs can be used to treat acquired acute SCI with similar success. In addition to improved motor function, our studies demonstrate neuronal preservation in the spinal cords of treated animals. However, no engraftment of the transplanted cells has been identified suggesting that the observed neuroprotection is the result of PMSC paracrine secretion. Complete analysis of the PMSC secretome will allow us to identify the pathways involved in neuronal survival following injury. Therefore, for this study we propose two distinct but interrelated aims. First, we will perform complete characterization of the PMSC secretome, including cultured media and isolated exosomes. PMSC secretions will be analyzed for potentially therapeutic factors, including proteins, mRNA, miRNA, and metabolites. The PMSC secretome will then be assessed using a trio of established functional assays to determine the impact of cultured media and isolated exosomes on neuroprotection, angiogenesis, and immunomodulation. PMSCs found to be the most efficacious on in vitro functional testing will be utilized for the in vivo arm. The therapeutic capability of PMSCs or isolated exosomes will be assessed using a validated unilateral cervical spinal cord contusion rodent model. Following injury, Sprague-Dawley rats will be treated with either PMSCs or exosomes via intrathecal injection in proximity to the injury. All animals will be evaluated on skilled forelimb use, paw preference, gait analysis, and limb coordination. Animals will be euthanized at 8 weeks post-injury for histologic analysis, which will include volumetric analysis, grey and white matter preservation, and motor neuron preservation. Sham surgical animals and untreated injured animals will serve as controls. In this way, we intend to elucidate the mechanism of action behind the neuroprotective capabilities of PMSCs and develop a PMSC-derived treatment for acquired acute SCI. (CHN: SCIRTS chn:wdg)
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    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC


  • RCDC

    Regenerative Medicine

  • RCDC


  • RCDC

    Spinal Cord Injury

  • RCDC


  • RCDC


  • RCDC




  • Health Research Areas


  • Broad Research Areas

    Basic Science