TY - JOUR
T1 - Mesenchymal stem cell transplantation and DMEM administration in a 3NP rat model of Huntington's disease
T2 - Morphological and behavioral outcomes
AU - Rossignol, Julien
AU - Boyer, Cécile
AU - Lévèque, Xavier
AU - Fink, Kyle D.
AU - Thinard, Reynald
AU - Blanchard, Frédéric
AU - Dunbar, Gary L.
AU - Lescaudron, Laurent
N1 - Funding Information:
This work was supported by funding provided by grants from L’Association Huntington France (to LL and JR), the Field Neurosciences Institute and John G. Kulhavi Professorship (to GLD) and La Fondation Progreffe (to INSERM UMR 643). The authors thank V. Le Fol for technical assistance.
PY - 2011/3/1
Y1 - 2011/3/1
N2 - Transplantation of mesenchymal stem cells (MSCs) may offer a viable treatment for Huntington's disease (HD). We tested the efficacy of MSC transplants to reduce deficits in a 3-nitropropionic acid (3NP) rat model of HD. Five groups of rats (Sham, 3NP, 3NP+vehicle, 3NP+TPlow, 3NP+TPhigh), were given PBS or 3NP intraperitoneally, twice daily for 42 days. On day 28, rats in all groups except Sham and 3NP, received intrastriatal injections of either 200,000 MSCs (TPlow), 400,000 (TPhigh) MSCs or DMEM (VH, the vehicle for transplantation). MSCs survived 72 days without inducing a strong inflammatory response from the striatum. Behavioral sparing was observed on tests of supported-hindlimb-retraction, unsupported-hindlimb-retraction, visual paw placement and stepping ability for 3NP+TPlow rats and on the unsupported-hindlimb-retraction and rotarod tasks for 3NP+VH rats. Relative to 3NP controls, all treated groups were protected from 3NP-induced enlargement of the lateral ventricles. In vitro, MSCs expressed transcripts for numerous neurotrophic factors. In vivo, increased striatal labeling in BDNF, collagen type-I and fibronectin (but not GDNF or CNTF) was observed in the brains of MSC-transplanted rats but not in DMEM-treated rats. In addition, none of the transplanted MSCs expressed neural phenotypes. These findings suggest that factors other than neuronal replacement underlie the behavioral sparing observed in 3NP rats after MSC transplantation.
AB - Transplantation of mesenchymal stem cells (MSCs) may offer a viable treatment for Huntington's disease (HD). We tested the efficacy of MSC transplants to reduce deficits in a 3-nitropropionic acid (3NP) rat model of HD. Five groups of rats (Sham, 3NP, 3NP+vehicle, 3NP+TPlow, 3NP+TPhigh), were given PBS or 3NP intraperitoneally, twice daily for 42 days. On day 28, rats in all groups except Sham and 3NP, received intrastriatal injections of either 200,000 MSCs (TPlow), 400,000 (TPhigh) MSCs or DMEM (VH, the vehicle for transplantation). MSCs survived 72 days without inducing a strong inflammatory response from the striatum. Behavioral sparing was observed on tests of supported-hindlimb-retraction, unsupported-hindlimb-retraction, visual paw placement and stepping ability for 3NP+TPlow rats and on the unsupported-hindlimb-retraction and rotarod tasks for 3NP+VH rats. Relative to 3NP controls, all treated groups were protected from 3NP-induced enlargement of the lateral ventricles. In vitro, MSCs expressed transcripts for numerous neurotrophic factors. In vivo, increased striatal labeling in BDNF, collagen type-I and fibronectin (but not GDNF or CNTF) was observed in the brains of MSC-transplanted rats but not in DMEM-treated rats. In addition, none of the transplanted MSCs expressed neural phenotypes. These findings suggest that factors other than neuronal replacement underlie the behavioral sparing observed in 3NP rats after MSC transplantation.
KW - 3NP intoxication
KW - DMEM
KW - Huntington's disease
KW - Mesenchymal stem cells
KW - Transplantation
KW - Trophic factors
UR - http://www.scopus.com/inward/record.url?scp=78650416363&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2010.11.006
DO - 10.1016/j.bbr.2010.11.006
M3 - Article
C2 - 21070819
AN - SCOPUS:78650416363
VL - 217
SP - 369
EP - 378
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 2
ER -