Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington's Disease

Autor: Rachel E. DeJonge, Laurent Lescaudron, Gary L. Dunbar, Ming Lu, Aaron Antcliff, Allison C. Moore, Xavier Lévêque, Lucas D. Huffman, Andrew T. Crane, Darren Story, Dylan J. Dues, Julien Rossignol, Phillip A. Starski, Kyle D. Fink
Přispěvatelé: Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Field Neurosciences Laboratory for Restorative Neurology [Mount Pleasant, MI, USA] (Program in Neuroscience ), Central Michigan University (CMU), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Field Neurosciences Institute, St. Mary's of Michigan, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR Odontologie, Centre Hospitalier Universitaire Hôtel-Dieu de Nantes (CHU Hôtel-Dieu), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Jehan, Frederic
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
Huntington's Disease
Pathology
Striosome
Medical Biotechnology
Convulsants
Striatum
Neurodegenerative
medicine.disease_cause
Regenerative Medicine
Rats
Sprague-Dawley
0302 clinical medicine
Transduction
Genetic
Adenovirus
Induced pluripotent stem cell
0303 health sciences
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
iPSC
Stem cell
Behavior
Animal
[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology
3-Nitropropionic acid
[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology
General Medicine
Anatomy
Nitro Compounds
3. Good health
Huntington Disease
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Neurological
Female
Development of treatments and therapeutic interventions
Huntington’s disease
medicine.medical_specialty
Induced Pluripotent Stem Cells
Clinical Sciences
Neuropathology
Biology
Adenoviridae
03 medical and health sciences
Transduction
Rare Diseases
Huntington's disease
Genetic
medicine
Animals
Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells
030304 developmental biology
Behavior
Transplantation
Stem Cell Research - Induced Pluripotent Stem Cell
5.2 Cellular and gene therapies
Animal
Neurosciences
Cell Biology
medicine.disease
Stem Cell Research
Corpus Striatum
Rats
Brain Disorders
Disease Models
Animal
Disease Models
Sprague-Dawley
Biochemistry and Cell Biology
Propionates
030217 neurology & neurosurgery
Developmental Biology
Stem Cell Transplantation
Zdroj: Stem Cells Translational Medicine
Stem Cells Translational Medicine, Wiley, 2014, 3 (5), pp.620-631. ⟨10.5966/sctm.2013-0151⟩
Stem cells translational medicine, vol 3, iss 5
Stem Cells Translational Medicine, 2014, 3 (5), pp.620-631. ⟨10.5966/sctm.2013-0151⟩
ISSN: 2157-6564
2157-6580
DOI: 10.5966/sctm.2013-0151⟩
Popis: Induced pluripotent stem cells (iPSCs) show considerable promise for cell replacement therapies for Huntington's disease (HD). Our laboratory has demonstrated that tail-tip fibroblasts, reprogrammed into iPSCs via two adenoviruses, can survive and differentiate into neuronal lineages following transplantation into healthy adult rats. However, the ability of these cells to survive, differentiate, and restore function in a damaged brain is unknown. To this end, adult rats received a regimen of 3-nitropropionic acid (3-NP) to induce behavioral and neuropathological deficits that resemble HD. At 7, 21, and 42 days after the initiation of 3-NP or vehicle, the rats received intrastriatal bilateral transplantation of iPSCs. All rats that received 3-NP and vehicle treatment displayed significant motor impairment, whereas those that received iPSC transplantation after 3-NP treatment had preserved motor function. Histological analysis of the brains of these rats revealed significant decreases in optical densitometric measures in the striatum, lateral ventricle enlargement, as well as an increase in striosome size in all rats receiving 3-NP when compared with sham rats. The 3-NP-treated rats given transplants of iPSCs in the 7- or 21-day groups did not exhibit these deficits. Transplantation of iPSCs at the late-stage (42-day) time point did not protect against the 3-NP-induced neuropathology, despite preserving motor function. Transplanted iPSCs were found to survive and differentiate into region-specific neurons in the striatum of 3-NP rats, at all transplantation time points. Taken together, these results suggest that transplantation of adenovirus-generated iPSCs may provide a potential avenue for therapeutic treatment of HD.
Databáze: OpenAIRE
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