title: Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.
abstract: Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs) would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Chongno-Gu, Seoul, Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.forename: Juyoun
authors.initials: J
authors.lastname: Jin
authors.forename: Bong Gu
authors.initials: BG
authors.lastname: Kang
authors.forename: Se Jeong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kang Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Heekyoung
authors.initials: H
authors.lastname: Yang
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Cho
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Im
authors.forename: Dong-Sup
authors.initials: DS
authors.lastname: Lee
authors.forename: Do-Hoon
authors.initials: DH
authors.lastname: Lim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Um
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Jung-Ii
authors.initials: JI
authors.lastname: Lee
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000150:complications / Q000532:radiotherapy / Q000628:therapy*; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D054338:Cell Transdifferentiation; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control* / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects; D033581:Stem Cell Transplantation / Q000379:methods*