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Human Oligodendrogenic Neural Progenitor Cells Delivered with Chondroitinase ABC Facilitate Functional Repair of Chronic Spinal Cord Injury

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...

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Published in:Stem cell reports 2018-12, Vol.11 (6), p.1433-1448
Main Authors: Nori, Satoshi, Khazaei, Mohamad, Ahuja, Christopher S., Yokota, Kazuya, Ahlfors, Jan-Eric, Liu, Yang, Wang, Jian, Shibata, Shinsuke, Chio, Jonathon, Hettiaratchi, Marian H., Führmann, Tobias, Shoichet, Molly S., Fehlings, Michael G.
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Language:English
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Summary: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. [Display omitted] •Sustained biomaterial delivery of ChABC successfully degraded CSPGs•XMC-ChABC promoted differentiation of oNPCs to more oligodendrocytes•XMC-ChABC increased the long-term survival and integration of grafted oNPCs•XMC-ChABC and oNPC combinatorial therapy is a promising treatment for chronic SCI Fehlings and colleagues investigated the use of directly reprogrammed human neural progenitor cells biased toward an oligodendrogenic fate (oNPCs) combined with sustained delivery of chondroitinase ABC to treat chronic spinal cord injury in an immunodeficient rat model. This combinatorial therapy increased long-term survival of oNPCs, facilitated greater oligodendrocyte differentiation, remyelination of the spared axons by engrafted oNPCs, and neurobehavioral recovery.
ISSN:2213-6711
2213-6711
DOI:10.1016/j.stemcr.2018.10.017