Open AccessTransplants of Adult Mesenchymal and Neural Stem Cells Provide Neuroprotection and Behavioral Sparing in a Transgenic Rat Model of Huntington's Disease
Author(s) -
Rossignol Julien,
Fink Kyle,
Davis Kendra,
Clerc Steven,
Crane Andrew,
Matchynski Jessica,
Lowrance Steven,
Bombard Matthew,
DeKorver Nicholas,
Lescaudron Laurent,
Dunbar Gary L.
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1508
Subject(s) - biology , mesenchymal stem cell , neuroprotection , stem cell , transplantation , neural stem cell , neurotrophic factors , immune system , huntington's disease , immunology , microbiology and biotechnology , neuroscience , disease , pathology , medicine , genetics , receptor
Stem cells have gained significant interest as a potential treatment of neurodegenerative diseases, including Huntington's disease (HD). One source of these cells is adult neural stem cells (aNSCs), which differentiate easily into neuronal lineages. However, these cells are vulnerable to immune responses following transplantation. Another source is bone‐marrow‐derived mesenchymal stem cells (MSCs), which release neurotrophic factors and anti‐inflammatory cytokines following transplantation, and are less vulnerable to rejection. The goal of this study was to compare the efficacy of transplants of MSCs, aNSCs, or cotransplants of MSCs and aNSCs for reducing deficits in a transgenic rat model of HD. HD rats received intrastriatal transplantations of 400,000 MSCs, aNSCs, or a combination of MSCs/aNSCs, while wild‐type and HD controls were given vehicle. Rats were tested on the rotarod over the course of 20 weeks. The results indicated that transplants of: (a) aNSCs produced a strong immune response and conferred short‐term behavioral benefits; (b) MSCs elicited a relatively weak immune response, and provided a longer term behavioral benefit; and (c) combined MSCs and aNSCs conferred long‐term behavioral benefits and increased survival of the transplanted aNSCs. The finding that cotransplanting MSCs with aNSCs can prolong aNSC survival and provide greater behavioral sparing than when the transplants contains only aNSCs suggests that MSCs are capable of creating a more suitable microenvironment for aNSC survival. This cotransplantation strategy may be useful as a future therapeutic option for treating HD, especially if long‐term survival of differentiated cells proves to be critically important for preserving lasting functional outcomes. S tem C ells 2014;32:500–509