Neuroprotection by GDNF-secreting stem cells in a Huntington's disease model: optical neuroimage tracking of brain-grafted cells.
The use of stem cells for reconstructive or neuroprotective strategies can benefit from new advances in neuroimaging techniques to track grafted cells. In the present work, we analyze the potential of a neural stem cell (NSC) line, which stably expresses the glial cell line-derived neurotrophic factor (GDNF) and the firefly luciferase gene (GDNF/Luc-NSC), for cell therapy in a Huntington's disease mouse model. Our results show that detection of light photons is an effective method to quantify the proliferation rate and to characterize the migration pathways of transplanted NSCs. Intravenous administration of luciferine, the luciferase substract, into the grafted animals allowed the detection of implanted cells in real time by an optical neuroimaging methodology, overpassing the limits of serial histological analyses. We observed that transplanted GDNF/Luc-NSCs survive after grafting and expand more when transplanted in quinolinate-lesioned nude mouse striata than when transplanted in non-lesioned mice. We also demonstrate that GDNF/Luc-NSCs prevent the degeneration of striatal neurons in the excitotoxic mouse model of Huntington's disease and reduce the amphetamine-induced rotational behavior in mice bearing unilateral lesions.
Pineda
J R
JR
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
Rubio
N
N
Akerud
P
P
Urbán
N
N
Badimon
L
L
Arenas
E
E
Alberch
J
J
Blanco
J
J
Canals
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D015316:Genetic Therapy / Q000379:methods*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008156:Luciferases / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic / Q000379:methods
D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D008156:Luciferases