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Project

Identity-function definitions for transplantable human Schwann cells

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
Cell transplantation is at the forefront of regenerative medicine to repair the injured spinal cord. Schwann cells (SCs) have been extensively used for CNS repair after spinal cord injury (SCI) due to their axon growth promoting effects and roles in re-myelination and immunomodulation. Based on almost 3 decades of collective basic and pre-clinical research, a team of researchers at The Miami Project to Cure Paralysis received FDA approval to conduct a clinical trial aimed at testing safety aspects of autologous SC transplantation in SCI patients. This trial has been underway since 2012. This proposal, which is aimed at developing genomic tools for the molecular identification of human SCs, is directly relevant to the continued use of autologous SCs in clinical therapy, as the FDA requires that later phases of clinical investigations include an accurate identity/function assessment of the cells prior to their use in human patients. The feasibility to transplant autologous SCs relies on methods that allow the isolation, purification and expansion of adult SCs to the high numbers required for cell therapy use. The standard assignation of phenotype of a human SC population is typically based on immuno-detection of phenotypic markers deemed specific to the SC lineage. Yet, the reliability of cell identification by means of marker detection is questionable in the absence of functional data demonstrating that a given batch of cells can effectively differentiate, ensheathe axons and form myelin, all of which requires assessment by means of functional assays done in vitro and/or in vivo. If human SC transplantation moves into efficacy testing in Phase III trials, a regulatory requirement on determination of cell function is imposed by the FDA. This requires the implementation of ad hoc potency assays that provide a measure of biological activity. Bioassays able to examine axon ensheathment and/or myelination, which are the most distinctive attributes that define the SC phenotype, are not only laborious and time consuming but also hard to set up if adult human SCs are used. Thus, there is a pressing need to explore alternative methods to unambiguously characterize the phenotype of human SCs and establish identity-function relationships with predictive potential for therapeutic value. The advent of technologies such as whole transcriptome sequencing (RNA-seq) has enabled a broader and unequivocal description of a cell’s complete RNA expression profile. Thus, the short-term goal of this project is to determine the human SC’s transcriptome through RNA-seq followed by extensive bioinformatics and statistical analysis of the coding and non-coding RNAs. In the long-term, this project seeks to contribute to the development of innovative and robust tools for potency assay development. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    0604 Genetics

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Biotechnology

  • RCDC

    Human Genome

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Clinical Research

  • RCDC

    Clinical Trials and Supportive Activities

  • RCDC

    Genetics

  • RCDC

    Neurodegenerative

  • RCDC

    Transplantation

  • HRCS HC

    Generic Health Relevance

  • HRCS HC

    Neurological

  • HRCS RAC

    5.2 Cellular and gene therapies

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Clinical Medicine and Science