Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury

被引:64
|
作者
Iwasaki, Motoyuki [1 ]
Wilcox, Jared T. [1 ,2 ]
Nishimura, Yusuke [1 ]
Zweckberger, Klaus [1 ]
Suzuki, Hidenori [1 ]
Wang, Jian [1 ]
Liu, Yang [1 ]
Karadimas, Spyridon K. [1 ,2 ]
Fehlings, Michael G. [1 ,2 ]
机构
[1] Toronto Western Hosp, Krembil Neurosci Ctr, Univ Hlth Network, Toronto, ON M5T 2S8, Canada
[2] Univ Toronto, Inst Med Sci, Univ Hlth Network, Toronto, ON M5S 1A8, Canada
基金
加拿大健康研究院;
关键词
Self-assembling nanofiber; Neural precursor cell; Cervical cord injury; Functional recovery; Tissue preservation; STEM-CELL; NEUROLOGICAL RECOVERY; CHONDROITINASE ABC; NANOFIBER SCAFFOLD; GLIAL SCAR; REGENERATION; TRANSPLANTATION; INFLAMMATION; AXONS; DYSFUNCTION;
D O I
10.1016/j.biomaterials.2013.12.019
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
While neural stem/progenitor cells (NPCs) show promise for traumatic spinal cord injury (SCI), their efficacy in cervical SCI remains to be established. Moreover, their application to SCI is limited by the challenges posed by the lesion including the glial scar and the post-traumatic cavitation. Given this background, we sought to examine the synergistic effect of self-assembling peptide (SAP) molecules, designed to optimize the post-traumatic CNS microenvironment, and NSCs in a clinically-relevant model of contusive/compressive cervical SCI. We injected K2(QL)6K2 (QL6) SAPs into the lesion epicenter 14 days after bilateral clip compression-induced cervical SCI in rats, combined with simultaneous transplantation of neural stem/progenitor cells (NPCs) intraspinally adjacent to the lesion epicenter. The QL6 SAPs reduced the volume of cystic cavitation in the spinal cord lesion. Simultaneously engrafted NPCs preserved motor neurons and attenuated perilesional inflammation. The combination of QL6 and NPCs promoted forelimb neurobehavioral recovery and was associated with significant improvement in forelimb print area and stride length. In summary, we report for the first time histologic and functional benefits in a clinically-relevant model of cervical SCI through the synergistic effects of combined SAP and NPCs. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2617 / 2629
页数:13
相关论文
共 50 条
  • [31] Predifferentiated embryonic stem cells promote functional recovery after spinal cord compressive injury
    Marques, Suelen Adriani
    Almeida, Fernanda Martins
    Fernandes, Aline Marie
    Souza, Cleide dos Santos
    Cadilhe, Daniel Veloso
    Rehen, Stevens Kastrup
    Blanco Martinez, Ana Maria
    BRAIN RESEARCH, 2010, 1349 : 115 - 128
  • [32] Human Neural Stem Cells Survive, Differentiate, and Promote Recovery of Function in a Mouse Unilateral Cervical Spinal Cord Injury Model
    Hooshmand, M. J.
    Fousek, K.
    Lucero, J.
    Nishi, R.
    Huang, K.
    Jadhaw, N.
    Dhillon, J.
    Perez, H.
    Uchida, N.
    Cummings, B. J.
    Anderson, A. J.
    CELL TRANSPLANTATION, 2012, 21 (04) : 781 - 781
  • [33] Neural Stem Cells Clonally Selected From Embryonic Stem Cells Promote Recovery After Spinal Cord Injury
    Mitchell, Robert
    Salewski, Ryan
    Fehlings, Michael
    JOURNAL OF NEUROSURGERY, 2013, 119 (02) : A542 - A542
  • [34] Multipotent hair follicle stem cells promote repair of spinal cord injury and recovery of walking function
    Amoh, Yasuyuki
    Li, Lingna
    Katsuoka, Kensei
    Hoffman, Robert M.
    CELL CYCLE, 2008, 7 (12) : 1865 - 1869
  • [35] Roles of ES Cell-Derived Gliogenic Neural Stem/Progenitor Cells in Functional Recovery after Spinal Cord Injury
    Kumagai, Gentaro
    Okada, Yohei
    Yamane, Junichi
    Nagoshi, Narihito
    Kitamura, Kazuya
    Mukaino, Masahiko
    Tsuji, Osahiko
    Fujiyoshi, Kanehiro
    Katoh, Hiroyuki
    Okada, Seiji
    Shibata, Shinsuke
    Matsuzaki, Yumi
    Toh, Satoshi
    Toyama, Yoshiaki
    Nakamura, Masaya
    Okano, Hideyuki
    PLOS ONE, 2009, 4 (11):
  • [36] Functional recovery secondary to neural stem/progenitor cells transplantation combined with treadmill training in mice with chronic spinal cord injury
    Tashiro, S.
    Nishimura, S.
    Iwai, H.
    Sugai, K.
    Shinozaki, M.
    Iwanami, A.
    Toyama, Y.
    Liu, M.
    Okano, H.
    Nakamura, M.
    JOURNAL OF THE NEUROLOGICAL SCIENCES, 2017, 381 : 4 - 4
  • [37] Metformin Activates Resident Neural Stem and Progenitor Cells, Reduces Inflammation and Improves Functional Recovery Following Spinal Cord Injury
    Gilbert, Emily
    Kehtari, Tarlan
    Morshead, Cindi
    FASEB JOURNAL, 2021, 35
  • [38] Allogeneic Neural Stem/Progenitor Cells Derived From Embryonic Stem Cells Promote Functional Recovery After Transplantation Into Injured Spinal Cord of Nonhuman Primates
    Iwai, Hiroki
    Shimada, Hiroko
    Nishimura, Soraya
    Kobayashi, Yoshiomi
    Itakura, Go
    Hori, Keiko
    Hikishima, Keigo
    Ebise, Hayao
    Negishi, Naoko
    Shibata, Shinsuke
    Habu, Sonoko
    Toyama, Yoshiaki
    Nakamura, Masaya
    Okano, Hideyuki
    STEM CELLS TRANSLATIONAL MEDICINE, 2015, 4 (07) : 708 - 719
  • [39] Synergistic Effect of Neural Stem Cells and Olfactory Ensheathing Cells on Repair of Adult Rat Spinal Cord Injury
    Wang, Gan
    Ao, Qiang
    Gong, Kai
    Zuo, Huancong
    Gong, Yandao
    Zhang, Xiufang
    CELL TRANSPLANTATION, 2010, 19 (10) : 1325 - 1337
  • [40] Ultramicrostructure of tissue repair in the rat with spinal cord injury following transplantation of neural stem cells
    Dai, Guanghui
    Liu, Xuebin
    Zhang, Zan
    Xu, Ruxiang
    SCIENTIFIC RESEARCH AND ESSAYS, 2011, 6 (01): : 118 - 124