Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats

Karim Mukhida, Behnam A. Baghbaderani, Murray Hong, Matthew Lewington, Timothy James Phillips, Marcus McLeod, Arindom Sen, Leo A. Behie, Ivar Mendez

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Object. Fetal tissue transplantation for Parkinson disease (PD) has, demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. Methods. Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8-10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. Results. The HNPCs isolated from various regions of thi neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. Conclusions. Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.

Original languageEnglish (US)
Article numberE7
JournalNeurosurgical Focus
Volume24
Issue number3-4
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Keywords

  • Bioreactor expansion
  • Differentiation
  • Migration
  • Neural precursor cell
  • Parkinson disease
  • Transplantation

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Mukhida, K., Baghbaderani, B. A., Hong, M., Lewington, M., Phillips, T. J., McLeod, M., Sen, A., Behie, L. A., & Mendez, I. (2008). Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats. Neurosurgical Focus, 24(3-4), [E7]. https://doi.org/10.3171/FOC/2008/24/3-4/E6