Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

被引:1
|
作者
Qu, Wenrui [1 ,2 ]
Wu, Xiangbing [1 ]
Wu, Wei [1 ]
Wang, Ying [1 ]
Sun, Yan [1 ]
Deng, Lingxiao [1 ]
Walker, Melissa [1 ]
Chen, Chen [1 ]
Dai, Heqiao [1 ]
Han, Qi [1 ]
Ding, Ying [1 ]
Xia, Yongzhi [1 ]
Smith, George [3 ]
Li, Rui [2 ]
Liu, Nai-Kui [1 ]
Xu, Xiao-Ming [1 ,4 ]
机构
[1] Indiana Univ Sch Med, Stark Neurosci Res Inst, Dept Neurol Surg, Spinal Cord & Brain Injury Res Grp, Indianapolis, IN 46202 USA
[2] Second Hosp Jilin Univ, Dept Hand Surg, Changchun, Jilin, Peoples R China
[3] Temple Univ, Sch Med, Shriners Hosp, Pediat Res Ctr, Philadelphia, PA USA
[4] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA
关键词
axonal regrowth; bladder function; chondroitinase ABC; functional recovery; glial scar; lentivirus; migration; Schwann cell; spinal cord injury; transplantation; SEEDED GUIDANCE CHANNELS; AXONAL REGENERATION; LOCOMOTOR RECOVERY; LESION; GRAFTS; REPAIR; RATS; DEMYELINATION; COMBINATION; MODULATION;
D O I
10.4103/NRR.NRR-D-23-01338
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.
引用
收藏
页码:1467 / 1482
页数:16
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