title: Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury.
abstract: The effect of transplantation dose on the spatiotemporal dynamics of human neural stem cell (hNSC) engraftment has not been quantitatively evaluated in the central nervous system. We investigated changes over time in engraftment/survival, proliferation, and migration of multipotent human central nervous system-derived neural stem cells (hCNS-SCns) transplanted at doses ranging from 10,000 to 500,000 cells in spinal cord injured immunodeficient mice. Transplant dose was inversely correlated with measures of donor cell proliferation at 2 weeks post-transplant (WPT) and dose-normalized engraftment at 16 WPT. Critically, mice receiving the highest cell dose exhibited an engraftment plateau, in which the total number of engrafted human cells never exceeded the initial dose. These data suggest that donor cell expansion was inversely regulated by target niche parameters and/or transplantation density. Investigation of the response of donor cells to the host microenvironment should be a key variable in defining target cell dose in pre-clinical models of CNS disease and injury.
authors: Sue & Bill Gross Stem Cell Center, USA; Physical & Medical Rehabilitation, USA; Institute for Memory Impairments & Neurological Disorders, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA. Electronic address: kpiltti@uci.edu.
authors: Katja M
authors: KM
authors: Piltti
authors: Sue & Bill Gross Stem Cell Center, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA.
authors: Sabrina N
authors: SN
authors: Avakian
authors: Sue & Bill Gross Stem Cell Center, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA.
authors: Gabriella M
authors: GM
authors: Funes
authors: Sue & Bill Gross Stem Cell Center, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA.
authors: Antoinette
authors: A
authors: Hu
authors: StemCells Inc., 7707 Gateway, Newark, CA 94560, USA.
authors: Nobuko
authors: N
authors: Uchida
authors: Sue & Bill Gross Stem Cell Center, USA; Physical & Medical Rehabilitation, USA; Institute for Memory Impairments & Neurological Disorders, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA.
authors: Aileen J
authors: AJ
authors: Anderson
authors: Sue & Bill Gross Stem Cell Center, USA; Physical & Medical Rehabilitation, USA; Institute for Memory Impairments & Neurological Disorders, USA; Anatomy & Neurobiology, University of California-Irvine, Irvine, CA 92697, USA.
authors: Brian J
authors: BJ
authors: Cummings
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D016867:Immunocompromised Host; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000628:therapy*; D014183:Transplantation, Heterologous
keywords: Cell dose; Migration; Proliferation; SCI; Stem cell niche dynamics; Stem cell transplantation; Survival; hNSC