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.
Lachapelle
François
F
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
Avellana-Adalid
Virginia
V
Nait-Oumesmar
Brahim
B
Baron-Van Evercooren
Anne
A
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