Collagen scaffold combined with human umbilical cord-derived mesenchymal stem cells promote functional recovery after scar resection in rats with chronic spinal cord injury

被引:65
作者
Wang, Nuo [1 ]
Xiao, Zhifeng [1 ]
Zhao, Yannan [1 ]
Wang, Bin [1 ]
Li, Xing [1 ]
Li, Jing [1 ]
Dai, Jianwu [1 ]
机构
[1] Chinese Acad Sci, Inst Genet & Dev Biol, Key Lab Mol Dev Biol, Beijing, Peoples R China
关键词
chronic spinal cord injury; collagen; functional recovery; human umbilical cord-derived mesenchymal stem cell; neural regeneration; surgical scar resection; MULTIPLE-SCLEROSIS; AXONAL GROWTH; GLIAL SCAR; REGENERATION; NEUROGENESIS; INHIBITION; NEURONS; REPAIR; MODEL; DIFFERENTIATION;
D O I
10.1002/term.2450
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Effective therapeutic strategies for treating chronic spinal cord injury (SCI) are currently unavailable. Scar tissue in the lesion area is a main inhibitory factor for axonal regeneration and repair of chronic SCI. In this study, scar tissue was surgically resected from adult rats with 12week chronic SCI and then collagen scaffold (NeuroRegen Scaffold; NRS) and human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were implanted into the resected cavity to repair chronic SCI. The results demonstrated that the locomotor function of rats was not affected by surgical scar resection, indicating its safety in treating chronic SCI. Implanting NRS and hUC-MSCs promoted locomotion in rats and improved cortical motor- and somatosensory-evoked potentials. Furthermore, implanting NRS and hUC-MSCs promoted neurofilament- and -tubulin-III-positive neural regeneration and remyelination, elicited -tubulin-III-positive neuron production in the lesion area and blocked astrocyte growth outside the lesion area. In conclusion, implanting NRS in combination with hUC-MSCs provided a beneficial microenvironment for neural regeneration, showing significant therapeutic effects for chronic SCI.
引用
收藏
页码:E1154 / E1163
页数:10
相关论文
共 37 条
[1]   The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats [J].
Bareyre, FM ;
Kerschensteiner, M ;
Raineteau, O ;
Mettenleiter, TC ;
Weinmann, O ;
Schwab, ME .
NATURE NEUROSCIENCE, 2004, 7 (03) :269-277
[2]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[3]   Repetitive Intrathecal Catheter Delivery of Bone Marrow Mesenchymal Stromal Cells Improves Functional Recovery in a Rat Model of Contusive Spinal Cord Injury [J].
Cizkova, Dasa ;
Novotna, Ivana ;
Slovinska, Lucia ;
Vanicky, Ivo ;
Jergova, Stanislava ;
Rosocha, Jan ;
Radonak, Jozef .
JOURNAL OF NEUROTRAUMA, 2011, 28 (09) :1951-1961
[4]   Functional regeneration beyond the glial scar [J].
Cregg, Jared M. ;
DePaul, Marc A. ;
Filous, Angela R. ;
Lang, Bradley T. ;
Tran, Amanda ;
Silver, Jerry .
EXPERIMENTAL NEUROLOGY, 2014, 253 :197-207
[5]   Neurogenesis in the adult spinal cord in an experimental model of multiple sclerosis [J].
Danilov, AI ;
Covacu, R ;
Moe, MC ;
Langmoen, IA ;
Johansson, CB ;
Olsson, T ;
Brundin, L .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2006, 23 (02) :394-400
[6]   Linear Ordered Collagen Scaffolds Loaded with Collagen-Binding Neurotrophin-3 Promote Axonal Regeneration and Partial Functional Recovery after Complete Spinal Cord Transection [J].
Fan, Juan ;
Xiao, Zhifeng ;
Zhang, Hongtian ;
Chen, Bing ;
Tang, Guoqiang ;
Hou, Xianglin ;
Ding, Wenyong ;
Wang, Bin ;
Zhang, Peng ;
Dai, Jianwu ;
Xu, Ruxiang .
JOURNAL OF NEUROTRAUMA, 2010, 27 (09) :1671-1683
[7]   Regeneration-associated genes decline in chronically injured rat sciatic motoneurons [J].
Gordon, Tessa ;
Tetzlaff, Wolfram .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2015, 42 (10) :2783-2791
[8]   Degenerative and spontaneous regenerative processes after spinal cord injury [J].
Hagg, T ;
Oudega, M .
JOURNAL OF NEUROTRAUMA, 2006, 23 (3-4) :264-280
[9]   Repair of chronic spinal cord injury [J].
Houle, JD ;
Tessler, A .
EXPERIMENTAL NEUROLOGY, 2003, 182 (02) :247-260
[10]   DEMONSTRATION OF THE POTENTIAL FOR CHRONICALLY INJURED NEURONS TO REGENERATE AXONS INTO INTRASPINAL PERIPHERAL-NERVE GRAFTS [J].
HOULE, JD .
EXPERIMENTAL NEUROLOGY, 1991, 113 (01) :1-9