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Project

Determination of Optimal Neural Progenitor Cell Sources for SCI Studies

Funder: Craig H Neilsen Foundation

Funding period
USD 150 K
Funding amount
Abstract
Neural progenitor cells (NPCs) grafted into sites of spinal cord injury (SCI) differentiate into mature neurons that integrate into injured spinal cord circuitry, enable robust regeneration, and support functional recovery. However, there is limited understanding of how distinct subtypes of graft neurons can integrate into various neural circuits. We have shown that grafts of NPCs derived from regionally-restricted areas of embryonic spinal cord differ in their dorsal/ventral neuronal identities upon maturation. We now show that the developmental stage of donor NPCs is also a critical factor determining graft cell fates: earlier-stage NPCs give rise to greater proportions of ventral interneurons, and later-stage NPCs give rise to greater proportions of dorsal interneurons, in vitro and in vivo. This suggests that distinct developmental stages of NPCs may be more ideal for reconstructing sensory or motor circuitry. We hypothesize that earlier-stage NPCs will provide more ideal substrates for host motor axon regeneration, and later-stage NPCs will enable more extensive regeneration of host sensory axons. We will test this by grafting developmentally-restricted NPCs into sites of SCI, characterizing graft cell fates, assessing integration with host systems, mapping connectivity of specific graft neuronal subtypes, and assessing effects on recovery of function. The overall objective of this proposal is to establish a new framework defining the key components in NPC grafts that support regeneration of functionally important host motor and sensory systems. Findings of this work will greatly contribute to our understanding of the cellular mechanisms by which NPC grafts might support functional recovery after SCI, and will establish important new guidelines for engineering new and effective clinically-relevant cell sources for ultimate translation to clinical trials. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Stem Cell Research

  • RCDC

    Neurodegenerative

  • RCDC

    Stem Cell Research - Nonembryonic - Non-Human

  • RCDC

    Transplantation

  • HRCS HC

    Neurological

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science