title: Injury to the spinal cord niche alters the engraftment dynamics of human neural stem cells.
abstract: 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.
authors.affiliation: Sue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, CA 92697, USA ; MIND Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA ; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sontag
authors.affiliation: Stem Cells, Inc., Newark, CA 94560, USA.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Uchida
authors.affiliation: Sue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, CA 92697, USA ; MIND Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA ; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA ; Department of Physical Medicine and Rehabilitation, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cummings
authors.affiliation: Sue and Bill Gross Stem Cell Center, University of California, Irvine, Irvine, CA 92697, USA ; MIND Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA ; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA ; Department of Physical Medicine and Rehabilitation, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Aileen J
authors.initials: AJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D009836:Oligodendroglia / Q000166:cytology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014183:Transplantation, Heterologous