Journal
STEM CELL REPORTS
Volume 11, Issue 6, Pages 1433-1448Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2018.10.017
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Funding
- Industry Sponsored Collaborative Research Grant
- New World Laboratories Inc.
- Canadian Institutes of Health Research (CIHR)
- Halbert Chair in Neural Repair and Regeneration
- DeZwirek Foundation
- Tier 1 Canada Research Chair
- Krembil Foundation
- Japan Society for the Promotion of Science Overseas Research Fellowships
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Treatment of chronic spinal cord injury (SCI) is challenging due to cell loss, cyst formation, and the glial scar. Previously, we reported on the therapeutic potential of a neural progenitor cell (NPC) and chondroitinase ABC (ChABC) combinatorial therapy for chronic SCI. However, the source of NPCs and delivery system required for ChABC remained barriers to clinical application. Here, we investigated directly reprogrammed human NPCs biased toward an oligodendrogenic fate (oNPCs) in combination with sustained delivery of ChABC using an innovative affinity release strategy in a crosslinked methylcellulose biomaterial for the treatment of chronic SCI in an immunodeficient rat model. This combinatorial therapy increased long-term survival of oNPCs around the lesion epicenter, facilitated greater oligodendrocyte differentiation, remyelination of the spared axons by engrafted oNPCs, enhanced synaptic connectivity with anterior horn cells and neurobehavioral recovery. This combinatorial therapy is a promising strategy to regenerate the chronically injured spinal cord.
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