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

67 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 (US)
Pages (from-to)318-334
Number of pages17
JournalProgress in Neurobiology
Volume85
Issue number3
DOIs
StatePublished - Jul 1 2008

Fingerprint

Teratocarcinoma
Stem Cells
Transplantation
Stroke
Cell Line
Therapeutics
Transplants
Cell Transplantation
Nerve Growth Factors
Glial Cell Line-Derived Neurotrophic Factor
Phase II Clinical Trials
Clinical Trials, Phase I
Brain
Tretinoin
Rodentia

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., ... 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

Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke. / Hara, Koichi; Yasuhara, Takao; Maki, Mina; Matsukawa, Noriyuki; Masuda, Tadashi; Yu, Seong Jin; Ali, Mohammed; Yu, Guolong; Xu, Lin; Kim, Seung U.; Hess, David C; Borlongan, Cesar V.

In: Progress in Neurobiology, Vol. 85, No. 3, 01.07.2008, p. 318-334.

Research output: Contribution to journalReview article

Hara, K, Yasuhara, T, Maki, M, Matsukawa, N, Masuda, T, Yu, SJ, Ali, M, Yu, G, Xu, L, Kim, SU, Hess, DC & Borlongan, CV 2008, 'Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke', Progress in Neurobiology, vol. 85, no. 3, pp. 318-334. https://doi.org/10.1016/j.pneurobio.2008.04.005
Hara, Koichi ; Yasuhara, Takao ; Maki, Mina ; Matsukawa, Noriyuki ; Masuda, Tadashi ; Yu, Seong Jin ; Ali, Mohammed ; Yu, Guolong ; Xu, Lin ; Kim, Seung U. ; Hess, David C ; Borlongan, Cesar V. / Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke. In: Progress in Neurobiology. 2008 ; Vol. 85, No. 3. pp. 318-334.
@article{488db23774c141c9a752774645890635,
title = "Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke",
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.",
keywords = "Behavioral recovery, Cerebral ischemia, Gene therapy, Graft survival, Neuronal differentiation, Neurotrophic factor, Stem cell",
author = "Koichi Hara and Takao Yasuhara and Mina Maki and Noriyuki Matsukawa and Tadashi Masuda and Yu, {Seong Jin} and Mohammed Ali and Guolong Yu and Lin Xu and Kim, {Seung U.} and Hess, {David C} and Borlongan, {Cesar V.}",
year = "2008",
month = "7",
day = "1",
doi = "10.1016/j.pneurobio.2008.04.005",
language = "English (US)",
volume = "85",
pages = "318--334",
journal = "Progress in Neurobiology",
issn = "0301-0082",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke

AU - Hara, Koichi

AU - Yasuhara, Takao

AU - Maki, Mina

AU - Matsukawa, Noriyuki

AU - Masuda, Tadashi

AU - Yu, Seong Jin

AU - Ali, Mohammed

AU - Yu, Guolong

AU - Xu, Lin

AU - Kim, Seung U.

AU - Hess, David C

AU - Borlongan, Cesar V.

PY - 2008/7/1

Y1 - 2008/7/1

N2 - 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.

AB - 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.

KW - Behavioral recovery

KW - Cerebral ischemia

KW - Gene therapy

KW - Graft survival

KW - Neuronal differentiation

KW - Neurotrophic factor

KW - Stem cell

UR - http://www.scopus.com/inward/record.url?scp=46449111075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46449111075&partnerID=8YFLogxK

U2 - 10.1016/j.pneurobio.2008.04.005

DO - 10.1016/j.pneurobio.2008.04.005

M3 - Review article

C2 - 18514379

AN - SCOPUS:46449111075

VL - 85

SP - 318

EP - 334

JO - Progress in Neurobiology

JF - Progress in Neurobiology

SN - 0301-0082

IS - 3

ER -