Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats

Stem Cell Research & Therapy

Pavla Jendelova²  Eva Sykova²  Meena Jhanwar-Uniyal³  Nataliya Romanyuk¹  Jiri Ruzicka²  Takashi Amemori¹ 

[1] Department of Neuroscience, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4, 142 20, Czech Republic;Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Plzenska 130/221, Prague 5, 150 00, Czech Republic;Department of Neurosurgery, New York Medical College, Valhalla 10595, NY, USA

关键词: Intrathecal injection;    Intraspinal injection;    Neural progenitors;    Cell application route;    Cell therapy;    Human induced pluripotent stem cells;    Spinal cord injury;   

Others  :  1235189
DOI  :  10.1186/s13287-015-0255-2

 received in 2015-10-19, accepted in 2015-12-02,  发布年份 2015

【 摘 要 】

Background

Stem cell treatment provides a promising therapy for patients with spinal cord injury (SCI). However, the applied stem cells exert their effects in different manners that are dependent on the route used for administration.

Methods

In the present study, we administered neural precursors derived from induced pluripotent stem cells (iPS-NPs) either intraspinally into the lesion center or intrathecally into the subarachnoid space of rats with a balloon-induced spinal cord compression lesion. Functional locomotor performance, cell survival, astrogliosis, axonal sprouting and the expression of endogenous neurotrophic growth factors were evaluated using behavioral tests (BBB, flat beam test, rotarod, plantar test), morphometric analysis, immunohistochemistry and qPCR.

Results

Both treatments facilitated the functional locomotor recovery of rats with SCI. iPS-NPs injected intraspinally survived well for 2 months and were positive for MAP2, while cells grafted intrathecally were undetectable at the site of administration or in the spinal cord tissue. Intraspinal implantation increased gray and white matter sparing and axonal sprouting and reduced astrogliosis, while intrathecal application resulted only in an improvement of white matter sparing and an increase in axonal sprouting, in parallel with no positive effect on the expression of endogenous neurotrophic growth factor genes or glial scar reduction.

Conclusions

Intrathecally grafted iPS-NPs had a moderate therapeutic benefit on SCI through a paracrine mechanism that does not require the cells to be present in the tissue; however, the extended survival of i.s. grafted cells in the spinal cord may promote long-term spinal cord tissue regeneration.

【 授权许可】

   
2015 Amemori et al.

【 图 表 】

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