L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells

Zhongqi Li; Diana Oganesyan; Rachael Mooney; Xianfang Rong; Matthew J. Christensen; David Shahmanyan; Patrick M. Perrigue; Joseph Benetatos; Lusine Tsaturyan; Soraya Aramburo; Alexander J. Annala; Yang Lu; Joseph Najbauer; Xiwei Wu; Michael E. Barish; David L. Brody; Karen S. Aboody; Margarita Gutova

doi:10.1016/j.stemcr.2016.07.013

L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells

Zhongqi Li, Diana Oganesyan, Rachael Mooney, Xianfang Rong, Matthew J. Christensen, David Shahmanyan, Patrick M. Perrigue, Joseph Benetatos, Lusine Tsaturyan, Soraya Aramburo, Alexander J. Annala, Yang Lu, Joseph Najbauer, Xiwei Wu, Michael E. Barish, David L. Brody, Karen S. Aboody, Margarita Gutova^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Pre-clinical studies indicate that neural stem cells (NSCs) can limit or reverse CNS damage through direct cell replacement, promotion of regeneration, or delivery of therapeutic agents. Immortalized NSC lines are in growing demand due to the inherent limitations of adult patient-derived NSCs, including availability, expandability, potential for genetic modifications, and costs. Here, we describe the generation and characterization of a new human fetal NSC line, immortalized by transduction with L-MYC (LM-NSC008) that in vitro displays both self-renewal and multipotent differentiation into neurons, oligodendrocytes, and astrocytes. These LM-NSC008 cells were non-tumorigenic in vivo, and migrated to orthotopic glioma xenografts in immunodeficient mice. When administered intranasally, LM-NSC008 distributed specifically to sites of traumatic brain injury (TBI). These data support the therapeutic development of immortalized LM-NSC008 cells for allogeneic use in TBI and other CNS diseases.

Original language	English
Pages (from-to)	483-495
Number of pages	13
Journal	Stem Cell Reports
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2016.07.013
State	Published - 13 Sep 2016
Externally published	Yes

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10.1016/j.stemcr.2016.07.013

Cite this

Li, Z., Oganesyan, D., Mooney, R., Rong, X., Christensen, M. J., Shahmanyan, D., Perrigue, P. M., Benetatos, J., Tsaturyan, L., Aramburo, S., Annala, A. J., Lu, Y., Najbauer, J., Wu, X., Barish, M. E., Brody, D. L., Aboody, K. S., & Gutova, M. (2016). L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells. Stem Cell Reports, 7(3), 483-495. https://doi.org/10.1016/j.stemcr.2016.07.013

@article{64693a2a019f44c39f8b853297ba4cc0,

title = "L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells",

abstract = "Pre-clinical studies indicate that neural stem cells (NSCs) can limit or reverse CNS damage through direct cell replacement, promotion of regeneration, or delivery of therapeutic agents. Immortalized NSC lines are in growing demand due to the inherent limitations of adult patient-derived NSCs, including availability, expandability, potential for genetic modifications, and costs. Here, we describe the generation and characterization of a new human fetal NSC line, immortalized by transduction with L-MYC (LM-NSC008) that in vitro displays both self-renewal and multipotent differentiation into neurons, oligodendrocytes, and astrocytes. These LM-NSC008 cells were non-tumorigenic in vivo, and migrated to orthotopic glioma xenografts in immunodeficient mice. When administered intranasally, LM-NSC008 distributed specifically to sites of traumatic brain injury (TBI). These data support the therapeutic development of immortalized LM-NSC008 cells for allogeneic use in TBI and other CNS diseases.",

author = "Zhongqi Li and Diana Oganesyan and Rachael Mooney and Xianfang Rong and Christensen, {Matthew J.} and David Shahmanyan and Perrigue, {Patrick M.} and Joseph Benetatos and Lusine Tsaturyan and Soraya Aramburo and Annala, {Alexander J.} and Yang Lu and Joseph Najbauer and Xiwei Wu and Barish, {Michael E.} and Brody, {David L.} and Aboody, {Karen S.} and Margarita Gutova",

note = "Publisher Copyright: {\textcopyright} 2016 The Authors",

year = "2016",

month = sep,

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doi = "10.1016/j.stemcr.2016.07.013",

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Li, Z, Oganesyan, D, Mooney, R, Rong, X, Christensen, MJ, Shahmanyan, D, Perrigue, PM, Benetatos, J, Tsaturyan, L, Aramburo, S, Annala, AJ, Lu, Y, Najbauer, J, Wu, X, Barish, ME, Brody, DL, Aboody, KS & Gutova, M 2016, 'L-MYC Expression Maintains Self-Renewal and Prolongs Multipotency of Primary Human Neural Stem Cells', Stem Cell Reports, vol. 7, no. 3, pp. 483-495. https://doi.org/10.1016/j.stemcr.2016.07.013

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AU - Li, Zhongqi

AU - Oganesyan, Diana

AU - Mooney, Rachael

AU - Rong, Xianfang

AU - Christensen, Matthew J.

AU - Shahmanyan, David

AU - Perrigue, Patrick M.

AU - Benetatos, Joseph

AU - Tsaturyan, Lusine

AU - Aramburo, Soraya

AU - Annala, Alexander J.

AU - Lu, Yang

AU - Najbauer, Joseph

AU - Wu, Xiwei

AU - Barish, Michael E.

AU - Brody, David L.

AU - Aboody, Karen S.

AU - Gutova, Margarita

PY - 2016/9/13

Y1 - 2016/9/13

N2 - Pre-clinical studies indicate that neural stem cells (NSCs) can limit or reverse CNS damage through direct cell replacement, promotion of regeneration, or delivery of therapeutic agents. Immortalized NSC lines are in growing demand due to the inherent limitations of adult patient-derived NSCs, including availability, expandability, potential for genetic modifications, and costs. Here, we describe the generation and characterization of a new human fetal NSC line, immortalized by transduction with L-MYC (LM-NSC008) that in vitro displays both self-renewal and multipotent differentiation into neurons, oligodendrocytes, and astrocytes. These LM-NSC008 cells were non-tumorigenic in vivo, and migrated to orthotopic glioma xenografts in immunodeficient mice. When administered intranasally, LM-NSC008 distributed specifically to sites of traumatic brain injury (TBI). These data support the therapeutic development of immortalized LM-NSC008 cells for allogeneic use in TBI and other CNS diseases.

AB - Pre-clinical studies indicate that neural stem cells (NSCs) can limit or reverse CNS damage through direct cell replacement, promotion of regeneration, or delivery of therapeutic agents. Immortalized NSC lines are in growing demand due to the inherent limitations of adult patient-derived NSCs, including availability, expandability, potential for genetic modifications, and costs. Here, we describe the generation and characterization of a new human fetal NSC line, immortalized by transduction with L-MYC (LM-NSC008) that in vitro displays both self-renewal and multipotent differentiation into neurons, oligodendrocytes, and astrocytes. These LM-NSC008 cells were non-tumorigenic in vivo, and migrated to orthotopic glioma xenografts in immunodeficient mice. When administered intranasally, LM-NSC008 distributed specifically to sites of traumatic brain injury (TBI). These data support the therapeutic development of immortalized LM-NSC008 cells for allogeneic use in TBI and other CNS diseases.

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