Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke

Koichi Hara, Takao Yasuhara, Mina Maki, Noriyuki Matsukawa, Tadashi Masuda, Seong Jin Yu, Mohammed Ali, Guolong Yu, Lin Xu, Seung U. Kim, David C. Hess, Cesar V. Borlongan

Research output: Contribution to journalReview article

77 Citations (Scopus)

Abstract

This review article discusses recent progress on the use of teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N cells, also called hNT cells) as graft source for cell transplantation in stroke. Laboratory evidence has demonstrated the therapeutic potential of NT2N cells in stroke therapy. Phase I and II clinical trials have shown the cells' feasibility, safety and tolerability profiles in stroke patients. Despite these novel features of NT2N cells, the transplantation regimen remains to be optimized. Moreover, determining the mechanisms underlying the grafts' beneficial effects, specifically demonstrating functional synaptic connections between host brain and NT2N cell grafts, warrants further examination. The major limiting factor for initiating a large clinical trial is the cells' highly potent proliferative property due to their cancerous origin, thereby raising the concern that these cells may revert to a neoplastic state over time after transplantation. To this end, we explored a proof-of-concept "retroviral" strategy to further establish the post-mitotic status of NT2N cells by transfecting these cells with the transcription factor Nurr1, in addition to the standard treatment with retinoic acid and mitotic inhibitors. This new cell line NT2N.Nurr1 displays an expedited neuronal commitment and secretes a high level of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF), and when transplanted into the rodent stroke brain expressed neuronal phenotype and reduced behavioral impairments which are comparable, if not more robust, than those produced by NT2N cells. Such highly potent neuronal lineage commitment and neurotrophic factor secretory function of NT2.Nurr1 cells make them an appealing graft source for transplantation therapy.

Original languageEnglish
Pages (from-to)318-334
Number of pages17
JournalProgress in Neurobiology
Volume85
Issue number3
DOIs
Publication statusPublished - Jul 1 2008
Externally publishedYes

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Keywords

  • Behavioral recovery
  • Cerebral ischemia
  • Gene therapy
  • Graft survival
  • Neuronal differentiation
  • Neurotrophic factor
  • Stem cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hara, K., Yasuhara, T., Maki, M., Matsukawa, N., Masuda, T., Yu, S. J., Ali, M., Yu, G., Xu, L., Kim, S. U., Hess, D. C., & Borlongan, C. V. (2008). Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke. Progress in Neurobiology, 85(3), 318-334. https://doi.org/10.1016/j.pneurobio.2008.04.005