Distinct efficacy of pre-differentiated versus intact fetal mesencephalon-derived human neural progenitor cells in alleviating rat model of Parkinson's disease

Xuan Wang, Yanyan Lu, Huanqing Zhang, Kun Wang, Qihua He, Yue Wang, Xianyu Liu, Linsong Li, Xiaomin Wang

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Neural progenitor cells have shown the effectiveness in the treatment of Parkinson's disease, but the therapeutic efficacy remains variable. One of important factors that determine the efficacy is the necessity of pre-differentiation of progenitor cells into dopaminergic neurons before transplantation. This study therefore investigated the therapeutic efficacy of mesencephalon-derived human neural progenitor cells with or without the pre-differentiation in alleviating a rat model of Parkinson's disease. We found that a combination of 50 ng/ml fibroblast growth factor 8, 10 ng/ml glial cell line-derived neurotrophic factor and 10 μM forskolin facilitated the differentiation of human fetal mesencephalic progenitor cells into dopaminergic neurons in vitro. More importantly, after transplanted into the striatum of parkinsonian rats, only pre-differentiated grafts resulted in an elevated production of dopamine in the transplanted site and the amelioration of behavioral impairments of the parkinsonian rats. Unlike pre-differentiated progenitors, grafted intact progenitors rarely differentiated into dopaminergic neurons in vivo and emigrated actively away from the transplanted site. These data demonstrates the importance of pre-differentiation of human progenitor cells before transplantation in enhancing therapeutic potency for Parkinson's disease.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalInternational Journal of Developmental Neuroscience
Volume22
Issue number4
DOIs
StatePublished - Jun 2004

Keywords

  • Cell differentiation
  • Cell transplantation
  • Central nervous system
  • DA
  • Dopaminergic neurons
  • IL
  • LIF
  • Migration
  • NPC
  • Neural progenitor cells
  • PD
  • Parkinson's disease
  • dopamine
  • interleukin
  • leukemia inhibitory factor
  • neural progenitor cell

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