Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor AB (PDGF AB) promote adult SVZ-derived oligodendrogenesis in vivo.
The capacity of multipotential progenitor cells of the adult mammalian forebrain to generate myelin-forming oligodendrocytes was tested by grafting fragments of different regions of the subventricular zone (SVZ) of the lateral ventricle and the striatum of 6-month-old wild-type mice into the brain of neonate shiverer and wild-type mice. Without growth factor treatment, only few cells of the rostral SVZ survived and formed myelin after engraftment. Treating donors prior to transplantation with a single intraperitoneal injection of epidermal growth factor, basic fibroblast growth factor 2 (FGF-2), and platelet-derived growth factor AB (PDGF(AB)) vigorously promoted the survival, migration, and differentiation of the grafted SVZ cells into myelin-forming oligodendrocytes. In situ, both growth factors expanded the constitutively proliferative PSA-NCAM+ population and favored their differentiation toward the neuronal and oligodendroglial cell fate. The adult central nervous system thus harbors a focal reservoir of FGF-2 and PDGF(AB)-responsive cells which are able to generate substantial amounts of myelin-forming oligodendrocytes in vivo, opening a new prospective area for therapy in demyelinating diseases.
Institut National de la Santé et de la Recherche Medicale, U546, Laboratoire des Affections de la Myéline et des Canaux Ioniques Musculaires, Institut Fédératif des Neurosciences, CHU Pitié-Salpêtrière, Paris, France. lachapel@ccr.jussieu.fr
François
F
Lachapelle
Virginia
V
Avellana-Adalid
Brahim
B
Nait-Oumesmar
Anne
A
Baron-Van Evercooren
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000637:transplantation*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D020547:Lateral Ventricles / Q000187:drug effects* / Q000637:transplantation; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D016548:Prosencephalon / Q000187:drug effects / Q000637:transplantation
D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; D016222:Fibroblast Growth Factor 2