Autologous transplantation of expanded neural precursor cells into the demyelinated monkey spinal cord.
The objective of this study was to establish if neural precursor cells could safely be developed from biopsy of the subventricular zone (SVZ) in the non-human primate (marmoset), and to determine their myelinating potential after autologous transplantation into a demyelinated lesion. Small amounts of tissue were safely collected from the subventricular-subependymal zone of the adult primate brain under ultrasonography without any neurological deficit. Neural precursor cells were isolated and expanded in the presence of mitogen in vitro. The dorsal columns of the adult marmoset spinal cord were demyelinated by X-irradiation and intraspinal injections of ethidium bromide in the center of the radiation field. Cell suspensions of the neural precursors were microinjected through a micropipette into the demyelinated lesion site in the spinal cord. Lesions were histologically examined 3 weeks after transplantation. Light and electron microscopic examination of plastic embedded sections revealed a significant number of myelinating profiles in the transplantation zone; no myelination was observed in control lesions. The myelinated axons had predominantly peripheral patterns of myelination. These results demonstrate that autologous transplantation of neural precursor cells in the adult nonhuman primate can remyelinate demyelinated central nervous system (CNS) axons, thus suggesting the potential utility of such an approach in demyelinating lesions in humans.
Oka
Shinichi
S
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
Honmou
Osamu
O
Akiyama
Yukinori
Y
Sasaki
Masanori
M
Houkin
Kiyohiro
K
Hashi
Kazuo
K
Kocsis
Jeffery D
JD
D000818:Animals; D001706:Biopsy; D002144:Callithrix; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology*; D003711:Demyelinating Diseases / Q000473:pathology* / Q000628:therapy*; D004195:Disease Models, Animal; D008845:Microinjections; D009103:Multiple Sclerosis / Q000473:pathology / Q000628:therapy; D013116:Spinal Cord / Q000473:pathology*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous