Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation

Tongguang Wang; Elliot Choi; Maria Chiara G. Monaco; Emilie Campanac; Marie Medynets; Thao Do; Prashant Rao; Kory R. Johnson; Abdel G. Elkahloun; Gloria Von Geldern; Tory Johnson; Sriram Subramaniam; Dax Hoffman; Eugene Major; Avindra Nath

doi:10.1371/journal.pone.0081720

Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation

Tongguang Wang, Elliot Choi, Maria Chiara G. Monaco, Emilie Campanac, Marie Medynets, Thao Do, Prashant Rao, Kory R. Johnson, Abdel G. Elkahloun, Gloria Von Geldern, Tory Johnson, Sriram Subramaniam, Dax Hoffman, Eugene Major, Avindra Nath

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

24 Scopus citations

Abstract

Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine.

Original language	English (US)
Article number	e81720
Journal	PloS one
Volume	8
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0081720
State	Published - Nov 26 2013
Externally published	Yes

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Wang, T., Choi, E., Monaco, M. C. G., Campanac, E., Medynets, M., Do, T., Rao, P., Johnson, K. R., Elkahloun, A. G., Von Geldern, G., Johnson, T., Subramaniam, S., Hoffman, D., Major, E., & Nath, A. (2013). Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation. PloS one, 8(11), Article e81720. https://doi.org/10.1371/journal.pone.0081720

Wang, T, Choi, E, Monaco, MCG, Campanac, E, Medynets, M, Do, T, Rao, P, Johnson, KR, Elkahloun, AG, Von Geldern, G, Johnson, T, Subramaniam, S, Hoffman, D, Major, E & Nath, A 2013, 'Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation', PloS one, vol. 8, no. 11, e81720. https://doi.org/10.1371/journal.pone.0081720

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title = "Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation",

abstract = "Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine.",

author = "Tongguang Wang and Elliot Choi and Monaco, {Maria Chiara G.} and Emilie Campanac and Marie Medynets and Thao Do and Prashant Rao and Johnson, {Kory R.} and Elkahloun, {Abdel G.} and {Von Geldern}, Gloria and Tory Johnson and Sriram Subramaniam and Dax Hoffman and Eugene Major and Avindra Nath",

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AU - Medynets, Marie

AU - Do, Thao

AU - Rao, Prashant

AU - Johnson, Kory R.

AU - Elkahloun, Abdel G.

AU - Von Geldern, Gloria

AU - Johnson, Tory

AU - Subramaniam, Sriram

AU - Hoffman, Dax

AU - Major, Eugene

AU - Nath, Avindra

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AB - Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine.

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Derivation of neural stem cells from human adult peripheral CD34+ cells for an autologous model of neuroinflammation

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