Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells

The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs) into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of info...

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Main Authors: Christopher J. Sontag, Nobuko Uchida, Brian J. Cummings, Aileen J. Anderson
Format: Article
Language:English
Published: Elsevier 2014-05-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671114000848
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author Christopher J. Sontag
Nobuko Uchida
Brian J. Cummings
Aileen J. Anderson
author_facet Christopher J. Sontag
Nobuko Uchida
Brian J. Cummings
Aileen J. Anderson
author_sort Christopher J. Sontag
collection DOAJ
description The microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs) into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how NSCs differentially respond to intact versus damaged CNS. Furthermore, single, terminal histological endpoints predominate, providing limited insight into the spatiotemporal dynamics of NSC engraftment and migration. We investigated the early and long-term engraftment dynamics of human CNS stem cells propagated as neurospheres (hCNS-SCns) following transplantation into uninjured versus subacutely injured spinal cords of immunodeficient NOD-scid mice. We stereologically quantified engraftment, survival, proliferation, migration, and differentiation at 1, 7, 14, 28, and 98 days posttransplantation, and identified injury-dependent alterations. Notably, the injured microenvironment decreased hCNS-SCns survival, delayed and altered the location of proliferation, influenced both total and fate-specific migration, and promoted oligodendrocyte maturation.
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spelling doaj.art-4130ad301f6c47aaa93ef09514384e252022-12-21T19:31:59ZengElsevierStem Cell Reports2213-67112014-05-012562063210.1016/j.stemcr.2014.03.005Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem CellsChristopher J. Sontag0Nobuko Uchida1Brian J. Cummings2Aileen J. Anderson3Sue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, CA 92697, USAStem Cells, Inc., Newark, CA 94560, USASue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, CA 92697, USASue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, CA 92697, USAThe microenvironment is a critical mediator of stem cell survival, proliferation, migration, and differentiation. The majority of preclinical studies involving transplantation of neural stem cells (NSCs) into the CNS have focused on injured or degenerating microenvironments, leaving a dearth of information as to how NSCs differentially respond to intact versus damaged CNS. Furthermore, single, terminal histological endpoints predominate, providing limited insight into the spatiotemporal dynamics of NSC engraftment and migration. We investigated the early and long-term engraftment dynamics of human CNS stem cells propagated as neurospheres (hCNS-SCns) following transplantation into uninjured versus subacutely injured spinal cords of immunodeficient NOD-scid mice. We stereologically quantified engraftment, survival, proliferation, migration, and differentiation at 1, 7, 14, 28, and 98 days posttransplantation, and identified injury-dependent alterations. Notably, the injured microenvironment decreased hCNS-SCns survival, delayed and altered the location of proliferation, influenced both total and fate-specific migration, and promoted oligodendrocyte maturation.http://www.sciencedirect.com/science/article/pii/S2213671114000848
spellingShingle Christopher J. Sontag
Nobuko Uchida
Brian J. Cummings
Aileen J. Anderson
Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells
Stem Cell Reports
title Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells
title_full Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells
title_fullStr Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells
title_full_unstemmed Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells
title_short Injury to the Spinal Cord Niche Alters the Engraftment Dynamics of Human Neural Stem Cells
title_sort injury to the spinal cord niche alters the engraftment dynamics of human neural stem cells
url http://www.sciencedirect.com/science/article/pii/S2213671114000848
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AT brianjcummings injurytothespinalcordnichealterstheengraftmentdynamicsofhumanneuralstemcells
AT aileenjanderson injurytothespinalcordnichealterstheengraftmentdynamicsofhumanneuralstemcells