Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease.
Neural and mesenchymal stem cells have been proposed as alternative sources of cells for transplantation into the brain in neurodegenerative disorders. However, the endogenous factors controlling their engraftment within the injured parenchyma remain ill-defined. Here, we demonstrate significant engraftment of undifferentiated exogenous mesenchymal or neural stem cells throughout the lesioned area in a rat model for Huntington's disease, as late as 8 weeks post-transplantation. We show that stem cell factor (SCF), strongly up-regulated within host cells in the damaged striatum, is able to activate the SCF receptor c-kit and its signaling pathway and to promote the migration and proliferation of mesenchymal and neural stem cells in vitro. Furthermore, c-kit receptor blockade alters neural stem cell distribution within the lesioned striatum. Host SCF expression is observed in atypical cells expressing glial fibrillary acidic protein and doublecortin in the lesioned striatum and in migrating doublecortin-positive progenitors. Taken together, these data demonstrate that SCF produced in situ in the lesioned striatum is an important factor in promoting the engraftment of stem cells within the lesioned brain.
Bantubungi
Kadiombo
K
Laboratory of Neurophysiology, ULB-Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium. Kadiombo.Bantubungi@lille.inserm.fr
Blum
David
D
Cuvelier
Laetitia
L
Wislet-Gendebien
Sabine
S
Rogister
Bernard
B
Brouillet
Emmanuel
E
Schiffmann
Serge N
SN
D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004622:Embryo, Mammalian; D006816:Huntington Disease / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009930:Organic Chemicals / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019089:Stem Cell Factor / Q000494:pharmacology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000145:classification / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D009419:Nerve Tissue Proteins; D009930:Organic Chemicals; C070080:PKH 26; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit