ABC 软骨素酶联合人少突胶质前体细胞移植促进慢性脊髓损伤的功能修复

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

机构信息

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.

Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, ON M5T 2S8, Canada.

出版信息

Stem Cell Reports. 2018 Dec 11;11(6):1433-1448. doi: 10.1016/j.stemcr.2018.10.017. Epub 2018 Nov 21.

DOI:10.1016/j.stemcr.2018.10.017

PMID:30472009

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6294173/

Abstract

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.

摘要

治疗慢性脊髓损伤（SCI）具有挑战性，因为存在细胞损失、囊肿形成和神经胶质瘢痕。此前，我们报道了神经祖细胞（NPC）和软骨素酶 ABC（ChABC）联合治疗慢性 SCI 的治疗潜力。然而，NPC 的来源和 ChABC 的递送系统仍然是临床应用的障碍。在这里，我们研究了直接重编程的具有少突胶质细胞命运偏向的人 NPC（oNPC）与 ChABC 的持续递送相结合，使用交联甲基纤维素生物材料中的创新亲和释放策略，治疗免疫缺陷大鼠模型中的慢性 SCI。这种组合疗法增加了病变中心周围 oNPC 的长期存活，促进了更大的少突胶质细胞分化，植入的 oNPC 对未受影响的轴突进行髓鞘再生，增强了与前角细胞的突触连接和神经行为恢复。这种组合疗法是一种很有前途的策略，可以使慢性损伤的脊髓再生。