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Human Astrocytes Derived from Glial Restricted Progenitors Support Regeneration of the Injured Spinal Cord
Journal article   Open access   Peer reviewed

Human Astrocytes Derived from Glial Restricted Progenitors Support Regeneration of the Injured Spinal Cord

Christopher Haas and Itzhak Fischer
Journal of neurotrauma, v 30(12), pp 1035-1052
01 Jun 2013
PMID: 23635322
url
https://doi.org/10.1089/neu.2013.2915View
Published, Version of Record (VoR)Open Access (License Unspecified) Open

Abstract

Clinical Neurology Critical Care Medicine General & Internal Medicine Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
Cellular transplantation using neural stem cells and progenitors is a promising therapeutic strategy that has the potential to replace lost cells, modulate the injury environment, and create a permissive environment for the regeneration of injured host axons. Our research has focused on the use of human glial restricted progenitors (hGRP) and derived astrocytes. In the current study, we examined the morphological and phenotypic properties of hGRP prepared from the fetal central nervous system by clinically-approved protocols, compared with astrocytes derived from hGRP prepared by treatment with ciliary neurotrophic factor or bone morphogenetic protein 4. These differentiation protocols generated astrocytes that showed morphological differences and could be classified along an immature to mature spectrum, respectively. Despite these differences, the cells retained morphological and phenotypic plasticity upon a challenge with an alternate differentiation protocol. Importantly, when hGRP and derived astrocytes were transplanted acutely into a cervical dorsal column lesion, they survived and promoted regeneration of long ascending host sensory axons into the graft/lesion site, with no differences among the groups. Further, hGRP taken directly from frozen stocks behaved similarly and also supported regeneration of host axons into the lesion. Our results underscore the dynamic and permissive properties of human fetal astrocytes to promote axonal regeneration. They also suggest that a time-consuming process of pre-differentiation may not be necessary for therapeutic efficacy, and that the banking of large quantities of readily available hGRP can be an appropriate source of permissive cells for transplantation.

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Web of Science research areas
Clinical Neurology
Critical Care Medicine
Neurosciences
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