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

Abstract

BackgroundStem 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.MethodsIn 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.ResultsBoth 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.ConclusionsIntrathecally 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0255-2) contains supplementary material, which is available to authorized users.

Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Last, but not least, our analyses indicate that intraspinal implantation is an appropriate transplantation method, which was adopted in most of the included studies. These results are in accordance with recent publications [28,40] indicating that direct injection of human iPSC promotes locomotor recovery. However, this type of transplantation may cause additional damage leading to further damage to the injured spinal cord [41].…”

“…However, this type of transplantation may cause additional damage leading to further damage to the injured spinal cord [41]. Notably, one publication included in our meta-analysis [28] demonstrated that intrathecal injection had a moderate therapeutic benefit on SCI via a paracrine mechanism that does not require the cells to be present in the tissue. However, the relevant publications are too few to confirm the efficacy of this method.…”

Progress in the Use of Induced Pluripotent Stem Cell-Derived Neural Cells for Traumatic Spinal Cord Injuries in Animal Populations: Meta-Analysis and Review

“…Out of a total of 22 reports that assessed iPSC‐derived neural cells for SCI treatment, the following studies were incorporated into the meta‐analysis . A few studies were excluded, because statistical significance could not be verified, motor recovery was not assessed, used a different scale to assess motor recovery, or focused on a cervical SCI model.…”

“…Analysis 2 months post‐transplantation shows that iPSC‐NPCs injected intraspinal increased gray and white matter and axonal sprouting and reduced astrogliosis, promoting enhanced long‐term spinal cord regeneration. Transplantation intrathecal also showed improvement in white matter and axonal sprouting compared with control groups, indicating that transplantation in both locations has a therapeutic benefit . Our meta‐analysis did not include studies treating SCIs at the cervical level; however, future studies should consider them, as injuries at this site account for more than 60% of SCI cases in humans .…”

Meta-analysis of stem cell transplantation for reflex hypersensitivity after spinal cord injury

“…After a literature search conducted electronically and manually, the search strategy initially yielded 20 studies that met inclusion criteria (Abrams et al, 2009; Amemori et al, 2013, 2015; Biernaskie et al, 2007; Choi et al, 2013; Dagci et al, 2011; Furuya et al, 2009; Hofstetter et al, 2005; Karimi-Abdolrezaee et al, 2010; Kumagai et al, 2013; Lee et al, 2007; Macias et al, 2006; Nutt et al, 2013; Ritfeld et al, 2012; Salewski et al, 2015; Tao et al, 2013; Urdzikova et al, 2014; Watanabe et al, 2015; Yao et al, 2015; Yousefifard et al, 2016). These articles were retrieved for further assessment of titles, abstracts, and full-texts (if necessary).…”