Cargando…

Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Lu, Coleman, Ronald, Leang, Ronika, Tran, Ha, Kopf, Alexandra, Walsh, Craig M., Sears-Kraxberger, Ilse, Steward, Oswald, Macklin, Wendy B., Loring, Jeanne F., Lane, Thomas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050357/
https://www.ncbi.nlm.nih.gov/pubmed/24936469
http://dx.doi.org/10.1016/j.stemcr.2014.04.005
_version_ 1782319943277084672
author Chen, Lu
Coleman, Ronald
Leang, Ronika
Tran, Ha
Kopf, Alexandra
Walsh, Craig M.
Sears-Kraxberger, Ilse
Steward, Oswald
Macklin, Wendy B.
Loring, Jeanne F.
Lane, Thomas E.
author_facet Chen, Lu
Coleman, Ronald
Leang, Ronika
Tran, Ha
Kopf, Alexandra
Walsh, Craig M.
Sears-Kraxberger, Ilse
Steward, Oswald
Macklin, Wendy B.
Loring, Jeanne F.
Lane, Thomas E.
author_sort Chen, Lu
collection PubMed
description Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.
format Online
Article
Text
id pubmed-4050357
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-40503572014-06-16 Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis Chen, Lu Coleman, Ronald Leang, Ronika Tran, Ha Kopf, Alexandra Walsh, Craig M. Sears-Kraxberger, Ilse Steward, Oswald Macklin, Wendy B. Loring, Jeanne F. Lane, Thomas E. Stem Cell Reports Article Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments. Elsevier 2014-05-15 /pmc/articles/PMC4050357/ /pubmed/24936469 http://dx.doi.org/10.1016/j.stemcr.2014.04.005 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Chen, Lu
Coleman, Ronald
Leang, Ronika
Tran, Ha
Kopf, Alexandra
Walsh, Craig M.
Sears-Kraxberger, Ilse
Steward, Oswald
Macklin, Wendy B.
Loring, Jeanne F.
Lane, Thomas E.
Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
title Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
title_full Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
title_fullStr Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
title_full_unstemmed Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
title_short Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis
title_sort human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050357/
https://www.ncbi.nlm.nih.gov/pubmed/24936469
http://dx.doi.org/10.1016/j.stemcr.2014.04.005
work_keys_str_mv AT chenlu humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT colemanronald humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT leangronika humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT tranha humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT kopfalexandra humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT walshcraigm humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT searskraxbergerilse humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT stewardoswald humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT macklinwendyb humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT loringjeannef humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis
AT lanethomase humanneuralprecursorcellspromoteneurologicrecoveryinaviralmodelofmultiplesclerosis