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

Satoshi Nori; Mohamad Khazaei; Christopher S. Ahuja; Kazuya Yokota; Jan-Eric Ahlfors; Yang Liu; Jian Wang; Shinsuke Shibata; Jonathon Chio; Marian H. Hettiaratchi; Tobias Führmann; Molly S. Shoichet; Michael G. Fehlings

Stem Cell Reports (Dec 2018)

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

Satoshi Nori,
Mohamad Khazaei,
Christopher S. Ahuja,
Kazuya Yokota,
Jan-Eric Ahlfors,
Yang Liu,
Jian Wang,
Shinsuke Shibata,
Jonathon Chio,
Marian H. Hettiaratchi,
Tobias Führmann,
Molly S. Shoichet,
Michael G. Fehlings

Affiliations

Satoshi Nori: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada; Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinju-ku, Tokyo 160-8582, Japan
Mohamad Khazaei: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada
Christopher S. Ahuja: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada
Kazuya Yokota: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Jan-Eric Ahlfors: New World Laboratories Inc., 500 Boulevard Cartier Quest, Laval, QC H7V 5B7, Canada
Yang Liu: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada
Jian Wang: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada
Shinsuke Shibata: Electron Microscope Laboratory, Keio University School of Medicine, 35 Shinanomachi, Shinju-ku, Tokyo 160-8582, Japan
Jonathon Chio: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada
Marian H. Hettiaratchi: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada
Tobias Führmann: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada
Molly S. Shoichet: Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S 3E5, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON M5S 3H6, Canada; Institute of Biomaterials & Biomedical Engineering, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Institute of Medical Sciences, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada
Michael G. Fehlings: Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada; Institute of Medical Sciences, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Surgery and Spinal Program, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Department of Surgery, Division of Anatomy, Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Corresponding author

Journal volume & issue: Vol. 11, no. 6
pp. 1433 – 1448

Abstract

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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. : 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. Keywords: neural progenitor cells, oligodendrocyte, chronic spinal cord injury, glial scar, ChABC, cell transplantation, combinatorial therapy, remyelination, crosslinked methylcellulose hydrogel, regenerative medicine

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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