Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury

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 ner...

Full description

Bibliographic Details
Main Authors: Katja M. Piltti, Sabrina N. Avakian, Gabriella M. Funes, Antoinette Hu, Nobuko Uchida, Aileen J. Anderson, Brian J. Cummings
Format: Article
Language:English
Published: Elsevier 2015-09-01
Series:Stem Cell Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506115000926
_version_ 1828386829053722624
author Katja M. Piltti
Sabrina N. Avakian
Gabriella M. Funes
Antoinette Hu
Nobuko Uchida
Aileen J. Anderson
Brian J. Cummings
author_facet Katja M. Piltti
Sabrina N. Avakian
Gabriella M. Funes
Antoinette Hu
Nobuko Uchida
Aileen J. Anderson
Brian J. Cummings
author_sort Katja M. Piltti
collection DOAJ
description 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.
first_indexed 2024-12-10T05:44:05Z
format Article
id doaj.art-1136d545b49c40e9a699d4692a6dc2e2
institution Directory Open Access Journal
issn 1873-5061
1876-7753
language English
last_indexed 2024-12-10T05:44:05Z
publishDate 2015-09-01
publisher Elsevier
record_format Article
series Stem Cell Research
spelling doaj.art-1136d545b49c40e9a699d4692a6dc2e22022-12-22T02:00:12ZengElsevierStem Cell Research1873-50611876-77532015-09-0115234135310.1016/j.scr.2015.07.001Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injuryKatja M. Piltti0Sabrina N. Avakian1Gabriella M. Funes2Antoinette Hu3Nobuko Uchida4Aileen J. Anderson5Brian J. Cummings6Sue & Bill Gross Stem Cell Center, USASue & Bill Gross Stem Cell Center, USASue & Bill Gross Stem Cell Center, USASue & Bill Gross Stem Cell Center, USAStemCells Inc., 7707 Gateway, Newark, CA 94560, USASue & Bill Gross Stem Cell Center, USASue & Bill Gross Stem Cell Center, USAThe 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.http://www.sciencedirect.com/science/article/pii/S1873506115000926hNSCSCIStem cell niche dynamicsStem cell transplantationCell doseSurvivalProliferationMigration
spellingShingle Katja M. Piltti
Sabrina N. Avakian
Gabriella M. Funes
Antoinette Hu
Nobuko Uchida
Aileen J. Anderson
Brian J. Cummings
Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury
Stem Cell Research
hNSC
SCI
Stem cell niche dynamics
Stem cell transplantation
Cell dose
Survival
Proliferation
Migration
title Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury
title_full Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury
title_fullStr Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury
title_full_unstemmed Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury
title_short Transplantation dose alters the dynamics of human neural stem cell engraftment, proliferation and migration after spinal cord injury
title_sort transplantation dose alters the dynamics of human neural stem cell engraftment proliferation and migration after spinal cord injury
topic hNSC
SCI
Stem cell niche dynamics
Stem cell transplantation
Cell dose
Survival
Proliferation
Migration
url http://www.sciencedirect.com/science/article/pii/S1873506115000926
work_keys_str_mv AT katjampiltti transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury
AT sabrinanavakian transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury
AT gabriellamfunes transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury
AT antoinettehu transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury
AT nobukouchida transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury
AT aileenjanderson transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury
AT brianjcummings transplantationdosealtersthedynamicsofhumanneuralstemcellengraftmentproliferationandmigrationafterspinalcordinjury