Please enable JavaScript or talk to your local administrator to get JavaScript enabled.

Project

A Placental Stem Cell Derived Treatment for Acquired Spinal Cord Injury

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
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)
Similar projects All >
Sorted by: Start Date
Project list item
Neural Pathways and Recovery of Motor Function with Epidural Stimulation

Craig H Neilsen Foundation to Jessica Maria D'Amico, Claudia Angeli, Susan Harkema

USD 300,000
2019 - 2021
Project list item
Pioglitazone fosters neuroprotection via specific interaction with mitoNEET

Craig H Neilsen Foundation to Alexander G Rabchevsky, John Carib Gensel, Patrick Sullivan, Samirkumar Patel

USD 599,781
2017 - 2020
Project list item
Manipulating SUR subunits to treat sensory and motor dysfunction after SCI

Craig H Neilsen Foundation to Qing Yang, Qi Lin Cao

USD 300,000
2016 - 2020
Project list item
A Novel Combinatorial Therapy to Enhance Motor Recovery after SCI

Craig H Neilsen Foundation to Steve Perlmutter, Philip J Horner, Eberhard Fetz, Eliot Brenowitz, Samira Moorjani

USD 300,000
2016 - 2018
Project list item
MicroRNA-155 is a novel target for ameliorating SCI-induced neuropathic pain and locomotor deficits

Craig H Neilsen Foundation to Steven Maier, Andrew Gaudet

USD 300,000
2016 - 2019

System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Biotechnology

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Neurodegenerative

  • RCDC

    Pediatric

  • RCDC

    Transplantation

  • HRCS HC

    Neurological

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science