Transplantation of neural stem cells encapsulated in hydrogels improve functional recovery in a cauda equina lesion model

被引:1
作者
Fu, Zhiyi [1 ]
Wang, Huidong [1 ]
Wu, Yujie [1 ]
Zhu, Tong [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Shanghai Key Lab Orthopaed Implants,Sch Med, 639 Zhizaoju Rd, Shanghai 200011, Peoples R China
基金
中国国家自然科学基金;
关键词
Cauda equina lesion; neural stem cells; neonatal dorsal root ganglion; Hydrogel; SPINAL-CORD-INJURY; OLIGODENDROCYTES; DIFFERENTIATION; NEURONS; GRAFTS;
D O I
10.5582/bst.2020.03321
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
This study explored the therapeutic effects of transplantation of neural stem cells (NSCs) encapsulated in hydrogels in a cauda equina lesion model. NSCs were isolated from neonatal dorsal root ganglion (nDRG) and cultured in three-dimensional porous hydrogel scaffolds. Immunohistochemistry, transmission electron microscopy and TUNEL assay were performed to detect the differentiation capability, ultrastructural and pathological changes, and apoptosis of NSCs. Furthermore, the functional recovery of sensorimotor reflexes was determined using the tail-flick test. NSCs derived from DRG were able to proliferate to form neurospheres and mainly differentiate into oligodendrocytes in the three-dimensional hydrogel culture system. After transplantation of NSCs encapsulated in hydrogels, NSCs differentiated into oligodendrocytes, neurons or astrocytes in vivo. Moreover, NSCs engrafted on the hydrogels decreased apoptosis and alleviated the ultrastructural and pathological changes of injured cauda equina. Behavioral analysis showed that transplanted hydrogel-encapsulated NSCs decreased the tail-flick latency and showed a neuroprotective role on injured cauda equina. Our results indicate transplantation of hydrogel-encapsulated NSCs promotes stem cell differentiation into oligodendrocytes, neurons or astrocytes and contributes to the functional recovery of injured cauda equina, suggesting that NSCs encapsulated in hydrogels may be applied for the treatment of cauda equina injury.
引用
收藏
页码:360 / 367
页数:8
相关论文
共 33 条
[1]   Therapeutic potential of neurotrophic factors and neural stem cells against ischemic brain injury [J].
Abe, K .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2000, 20 (10) :1393-1408
[2]   Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain [J].
Andres, Robert H. ;
Horie, Nobutaka ;
Slikker, William ;
Keren-Gill, Hadar ;
Zhan, Ke ;
Sun, Guohua ;
Manley, Nathan C. ;
Pereira, Marta P. ;
Sheikh, Lamiya A. ;
McMillan, Erin L. ;
Schaar, Bruce T. ;
Svendsen, Clive N. ;
Bliss, Tonya M. ;
Steinberg, Gary K. .
BRAIN, 2011, 134 :1777-1789
[3]   Myelin and oligodendrocyte lineage cells in white matter pathology and plasticity after traumatic brain injury [J].
Armstrong, Regina C. ;
Mierzwa, Amanda J. ;
Sullivan, Genevieve M. ;
Sanchez, Maria A. .
NEUROPHARMACOLOGY, 2016, 110 :654-659
[4]   Human Neural Stem Cell Grafts Modify Microglial Response and Enhance Axonal Sprouting in Neonatal Hypoxic-Ischemic Brain Injury [J].
Daadi, Marcel M. ;
Davis, Alexis S. ;
Arac, Ahmet ;
Li, Zongjin ;
Maag, Anne-Lise ;
Bhatnagar, Rishi ;
Jiang, Kewen ;
Sun, Guohua ;
Wu, Joseph C. ;
Steinberg, Gary K. .
STROKE, 2010, 41 (03) :516-523
[5]  
Dias André Luiz Natálio, 2018, Rev. bras. ortop., V53, P107, DOI 10.1016/j.rboe.2017.11.006
[6]   Differentiation of neonatal dorsal root ganglion-derived neural stem cells into oligodendrocytes after intrathecal transplantation into a cauda equina lesion model [J].
Fu, Z. Y. ;
Shi, J. G. ;
Liu, N. ;
Jia, L. S. ;
Yuan, W. ;
Wang, Y. .
GENETICS AND MOLECULAR RESEARCH, 2013, 12 (04) :6092-6102
[7]   Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model [J].
Fuehrmann, T. ;
Tam, R. Y. ;
Ballarin, B. ;
Coles, B. ;
Donaghue, I. Elliott ;
van der Kooy, D. ;
Nagy, A. ;
Tator, C. H. ;
Morshead, C. M. ;
Shoichet, M. S. .
BIOMATERIALS, 2016, 83 :23-36
[8]   Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury [J].
Haus, Daniel L. ;
Lopez-Velazquez, Luci ;
Gold, Eric M. ;
Cunningham, Kelly M. ;
Perez, Harvey ;
Anderson, Aileen J. ;
Cummings, Brian J. .
EXPERIMENTAL NEUROLOGY, 2016, 281 :1-16
[9]   DRG-Derived Neural Progenitors Differentiate into Functional Enteric Neurons Following Transplantation in the Postnatal Colon [J].
Hu, Hui ;
Ding, Yuanyuan ;
Mu, Wenbo ;
Li, Ying ;
Wang, Yanpeng ;
Jiang, Weifang ;
Fu, Yong ;
Tou, Jinfa ;
Chen, Wei .
CELL TRANSPLANTATION, 2019, 28 (02) :157-169
[10]   Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1α/CXC chemokine receptor 4 pathway [J].
Imitola, J ;
Raddassi, K ;
Park, KI ;
Mueller, FJ ;
Nieto, M ;
Teng, YD ;
Frenkel, D ;
Li, JX ;
Sidman, RL ;
Walsh, CA ;
Snyder, EY ;
Khoury, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (52) :18117-18122