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

被引：93

作者：

Nori, Satoshi ^{[1
,2
]}

Khazaei, Mohamad ^{[1
]}

Ahuja, Christopher S. ^{[1
]}

Yokota, Kazuya ^{[1
,3
]}

Ahlfors, Jan-Eric ^{[4
]}

Liu, Yang ^{[1
]}

Wang, Jian ^{[1
]}

Shibata, Shinsuke ^{[5
]}

Chio, Jonathon ^{[1
]}

Hettiaratchi, Marian H. ^{[6
]}

Fuhrmann, Tobias ^{[6
]}

Shoichet, Molly S. ^{[6
,7
,8
,9
]}

Fehlings, Michael G. ^{[1
,9
,10
,11
,12
]}

机构：

[1] Univ Hlth Network, Div Genet & Dev, Krembil Res Inst, 60 Leonard Ave, Toronto, ON M5T 2S8, Canada

[2] Keio Univ, Sch Med, Dept Orthopaed Surg, Shinju Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[3] Kyushu Univ, Dept Orthopaed Surg, Grad Sch Med Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan

[4] New World Labs Inc, 500 Blvd Cartier Quest, Laval, PQ H7V 5B7, Canada

[5] Keio Univ, Electron Microscope Lab, Sch Med, Shinju Ku, 35 Shinanomachi, Tokyo 1608582, Japan

[6] Univ Toronto, Dept Chem Engn & Appl Chem, 200 Coll St, Toronto, ON M5S 3E5, Canada

[7] Univ Toronto, Dept Chem, 80 St George St, Toronto, ON M5S 3H6, Canada

[8] Univ Toronto, Inst Biomat & Biomed Engn, Terrence Donnelly Ctr Cellular & Biomol Res, 160 Coll St, Toronto, ON M5S 3E1, Canada

[9] Univ Toronto, Inst Med Sci, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada

[10] Univ Toronto, Dept Surg, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada

[11] Univ Toronto, Spinal Program, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada

[12] Univ Toronto, Dept Surg, Div Anat, Donnelly Ctr, 160 Coll St, Toronto, ON M5S 3E1, Canada

来源：

STEM CELL REPORTS | 2018年 / 11卷 / 06期

基金：

日本学术振兴会; 加拿大健康研究院;

关键词：

STEM-CELLS; STEM/PROGENITOR CELLS; REACTIVE ASTROCYTES; SCAR FORMATION; MOUSE MODEL; RECOVERY; TRANSPLANTATION; REGENERATION; DIFFERENTIATION; NEURONS;

D O I：

10.1016/j.stemcr.2018.10.017

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：1433 / 1448

页数：16

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