Caudalized human iPSC-derived neural progenitor cells produce neurons and glia but fail to restore function in an early chronic spinal cord injury model

Samuel E. Nutt, Eun Ah Chang, Steven T. Suhr, Laura O. Schlosser, Sarah E. Mondello, Chet T. Moritz, Jose B. Cibelli, Philip J. Horner

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Neural progenitor cells (NPCs) have shown modest potential and some side effects (e.g. allodynia) for treatment of spinal cord injury (SCI). In only a few cases, however, have NPCs shown promise at the chronic stage. Given the 1.275. million people living with chronic paralysis, there is a significant need to rigorously evaluate the cell types and methods for safe and efficacious treatment of this devastating condition. For the first time, we examined the pre-clinical potential of NPCs derived from human induced pluripotent stem cells (hiPSCs) to repair chronic SCI. hiPSCs were differentiated into region-specific (i.e. caudal) NPCs, then transplanted into a new, clinically relevant model of early chronic cervical SCI. We established the conditions for successful transplantation of caudalized hiPSC-NPCs and demonstrate their remarkable ability to integrate and produce multiple neural lineages in the early chronic injury environment. In contrast to prior reports in acute and sub-acute injury models, survival and integration of hiPSC-derived neural cells in the early chronic cervical model did not lead to significant improvement in forelimb function or induce allodynia. These data indicate that while hiPSCs show promise, future work needs to focus on the specific hiPSC-derivatives or co-therapies that will restore function in the early chronic injury setting.

Original languageEnglish (US)
Pages (from-to)491-503
Number of pages13
JournalExperimental Neurology
Volume248
DOIs
StatePublished - Oct 2013

Keywords

  • Induced pluripotent stem cells
  • Neural progenitor cells
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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