Skin-derived precursors generate myelinating Schwann cells that promote remyelination and functional recovery after contusion spinal cord injury

被引:236
作者
Biernaskie, Jeff
Sparling, Joseph S.
Liu, Jie
Shannon, Casey P.
Plemel, Jason R.
Xie, Yuanyun
Miller, Freda D.
Tetzlaff, Wolfram
机构
[1] Hosp Sick Children, MaRS Ctr, Dev & Stem Cell Biol Grp, Toronto, ON M5G 1L7, Canada
[2] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1L7, Canada
[3] Univ Toronto, Dept Physiol, Toronto, ON M5G 1L7, Canada
[4] Univ British Columbia, Int Collaborat Repair Discoveries, Vancouver, BC V6T 1Z4, Canada
[5] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada
[6] Univ British Columbia, Dept Surg, Vancouver, BC V6T 1Z4, Canada
关键词
skin-derived precursors; Schwann cells; spinal cord; transplantation; myelination; stem cells; recovery of function; neural stem cells; axonal growth; axonal regeneration;
D O I
10.1523/JNEUROSCI.1930-07.2007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Transplantation of exogenous cells is one approach to spinal cord repair that could potentially enhance the growth and myelination of endogenous axons. Here, we asked whether skin-derived precursors ( SKPs), a neural crest-like precursor that can be isolated and expanded from mammalian skin, could be used to repair the injured rat spinal cord. To ask this question, we isolated and expanded genetically tagged murine SKPs and either transplanted them directly into the contused rat spinal cord or differentiated them into Schwann cells ( SCs), and performed similar transplantations with the isolated, expanded SKP-derived SCs. Neuroanatomical analysis of these transplants 12 weeks after transplantation revealed that both cell types survived well within the injured spinal cord, reduced the size of the contusion cavity, myelinated endogenous host axons, and recruited endogenous SCs into the injured cord. However, SKP-derived SCs also provided a bridge across the lesion site, increased the size of the spared tissue rim, myelinated spared axons within the tissue rim, reduced reactive gliosis, and provided an environment that was highly conducive to axonal growth. Importantly, SKP-derived SCs provided enhanced locomotor recovery relative to both SKPs and forebrain subventricular zone neurospheres, and had no impact on mechanical or heat sensitivity thresholds. Thus, SKP-derived SCs provide an accessible, potentially autologous source of cells for transplantation into and treatment of the injured spinal cord.
引用
收藏
页码:9545 / 9559
页数:15
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