Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries

Advances in stem cell technology, including the use of induced pluripotent stem cells (iPSC) to produce neurons and glial cells, offer new hope for patients with neurological disease and injuries. Pet dogs with spinal cord injuries provide an important spontaneous animal model for evaluating new app...

Full description

Bibliographic Details
Main Authors: Lyndah Chow, Stephanie McGrath, Camila de Arruda Saldanha, Lawrence R. Whalen, Rebecca Packer, Steven Dow
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Veterinary Science
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2020.575938/full
_version_ 1828803397981044736
author Lyndah Chow
Stephanie McGrath
Camila de Arruda Saldanha
Lawrence R. Whalen
Rebecca Packer
Steven Dow
Steven Dow
author_facet Lyndah Chow
Stephanie McGrath
Camila de Arruda Saldanha
Lawrence R. Whalen
Rebecca Packer
Steven Dow
Steven Dow
author_sort Lyndah Chow
collection DOAJ
description Advances in stem cell technology, including the use of induced pluripotent stem cells (iPSC) to produce neurons and glial cells, offer new hope for patients with neurological disease and injuries. Pet dogs with spinal cord injuries provide an important spontaneous animal model for evaluating new approaches to stem cell therapy. Therefore, studies were conducted to identify optimal conditions for generating neural progenitor cells (NPC) from canine induced pluripotent stem cells (iPSC) for preliminary evaluation in animals with spinal cord injury. We found that canine NPC could be induced to differentiate into mature neural cells, including glia and neurons. In addition, canine NPC did not form teratomas when injected in NOD/SCID mice. In a pilot study, two dogs with chronic spinal cord injury underwent fluoroscopically guided intrathecal injections of canine NPC. In follow-up MRI evaluations, tumor formation was not observed at the injection sites. However, none of the animals experienced meaningful clinical or electrophysiological improvement following NPC injections. These studies provide evidence that canine iPSC can be used to generate NPC for evaluation in cellular therapy of chronic spinal cord injury in the dog spontaneous injury model. Further refinements in the cell implantation procedure are likely required to enhance stem cell treatment efficacy.
first_indexed 2024-12-12T07:22:00Z
format Article
id doaj.art-63c3bf64284d4adab9aa12f0399b9b0b
institution Directory Open Access Journal
issn 2297-1769
language English
last_indexed 2024-12-12T07:22:00Z
publishDate 2020-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Veterinary Science
spelling doaj.art-63c3bf64284d4adab9aa12f0399b9b0b2022-12-22T00:33:17ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692020-11-01710.3389/fvets.2020.575938575938Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord InjuriesLyndah Chow0Stephanie McGrath1Camila de Arruda Saldanha2Lawrence R. Whalen3Rebecca Packer4Steven Dow5Steven Dow6Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Center for Immune and Regenerative Medicine, Colorado State University, Ft. Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft. Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Center for Immune and Regenerative Medicine, Colorado State University, Ft. Collins, CO, United StatesDepartment of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft. Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft. Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Center for Immune and Regenerative Medicine, Colorado State University, Ft. Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Ft. Collins, CO, United StatesAdvances in stem cell technology, including the use of induced pluripotent stem cells (iPSC) to produce neurons and glial cells, offer new hope for patients with neurological disease and injuries. Pet dogs with spinal cord injuries provide an important spontaneous animal model for evaluating new approaches to stem cell therapy. Therefore, studies were conducted to identify optimal conditions for generating neural progenitor cells (NPC) from canine induced pluripotent stem cells (iPSC) for preliminary evaluation in animals with spinal cord injury. We found that canine NPC could be induced to differentiate into mature neural cells, including glia and neurons. In addition, canine NPC did not form teratomas when injected in NOD/SCID mice. In a pilot study, two dogs with chronic spinal cord injury underwent fluoroscopically guided intrathecal injections of canine NPC. In follow-up MRI evaluations, tumor formation was not observed at the injection sites. However, none of the animals experienced meaningful clinical or electrophysiological improvement following NPC injections. These studies provide evidence that canine iPSC can be used to generate NPC for evaluation in cellular therapy of chronic spinal cord injury in the dog spontaneous injury model. Further refinements in the cell implantation procedure are likely required to enhance stem cell treatment efficacy.https://www.frontiersin.org/articles/10.3389/fvets.2020.575938/fullneural progenitorinduced pluripotent stem cellspinal cord injuryspinal cord injectionteratoma
spellingShingle Lyndah Chow
Stephanie McGrath
Camila de Arruda Saldanha
Lawrence R. Whalen
Rebecca Packer
Steven Dow
Steven Dow
Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries
Frontiers in Veterinary Science
neural progenitor
induced pluripotent stem cell
spinal cord injury
spinal cord injection
teratoma
title Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries
title_full Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries
title_fullStr Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries
title_full_unstemmed Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries
title_short Generation of Neural Progenitor Cells From Canine Induced Pluripotent Stem Cells and Preliminary Safety Test in Dogs With Spontaneous Spinal Cord Injuries
title_sort generation of neural progenitor cells from canine induced pluripotent stem cells and preliminary safety test in dogs with spontaneous spinal cord injuries
topic neural progenitor
induced pluripotent stem cell
spinal cord injury
spinal cord injection
teratoma
url https://www.frontiersin.org/articles/10.3389/fvets.2020.575938/full
work_keys_str_mv AT lyndahchow generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries
AT stephaniemcgrath generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries
AT camiladearrudasaldanha generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries
AT lawrencerwhalen generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries
AT rebeccapacker generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries
AT stevendow generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries
AT stevendow generationofneuralprogenitorcellsfromcanineinducedpluripotentstemcellsandpreliminarysafetytestindogswithspontaneousspinalcordinjuries