Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury

Abstract

Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.

Odontogenic Tissue Generation Derived from Human Induced Pluripotent Stem Cells Using Tissue Engineering Application

“…3 -and cementum using tissue engineering application when the iPS cells are combined with tooth germ cells isolated from porcine third molar teeth in the late bell stage. This potential was confi rmed by the detection of human nuclei by the immunohistochemistry in consistent with other studies 22,24,25) . Recently, the ability of mouse iPS cells to form toothrelated structures has also been confirmed by recombination of mice incisor cells at the cap stage and tooth germ cells from ED14.5 mice in vivo 17) , although the fi nding that iPS cells alone do not form tooth tissues is consistent with our observations.…”

“…How did we recognize whether the transplanted iPS cells differentiated into ameloblasts, odontoblasts, and cementoblasts? We used immunohistochemical staining with human antibody, a wellestablished technique to recognize human cells 22,24,25) . Furthermore, porcine dental papilla cells and rat bone marrow cells were negatively stained with human nuclei in this study.…”

Axonal regeneration of different tracts following transplants of human glial restricted progenitors into the injured spinal cord in rats

“…In both studies, the CTB + axons grew into but not through the transplant indicating that hGRP provided permissive environment for the growth of sensory axons, but had only a limited effect on the regenerative capacity of these axons. Sensory axons have been shown to regenerate after SCI following other treatments such as administration of neurotrophic factors (Bradbury et al, 1999), reducing glial scar (Lee et al, 2010; Tan et al, 2006), transplants of Schwann cells and modified fibroblasts (Tuszynski et al, 1994; Xu et al, 1995b), neuronal and glial restricted progenitors (Bonner et al, 2011), and human stem cells (Hoeber et al, 2015). The ability of hGRP transplants to promote sensory axon growth into the lesion site can be exploited by combining them with neuronal progenitor cells to form a relay to reconnect the spinal cord as demonstrated for rodent cells (Bonner et al, 2011).…”

Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion

“…An anatomical connection between the L5 and L6 ventral nerve root is absent in almost 50% of the Wistar and Sprague-Dawley rats (Asato et al, 2000;Rigaud et al, 2008). This natural anatomical variation between individual rats accounts for at least some of the incidental variability in post-operative electophysiological measurements and the detection of variable numbers of uninjured neurons following retrograde tracing (Eggers et al, 2013;Torres-Espin et al, 2013;Hoeber et al, 2015).…”