title: Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation.
abstract: This study evaluated the clinical and pathologic effects of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the recovery from total body irradiation by comparing it with the effects of granulocyte-colony stimulating factor (G-CSF), an efficacious drug in the treatment of acute bone marrow radiation syndrome. BALB/c mice were treated with G-CSF or hUCB-MSCs after they were irradiated with 7 Gy cobalt-60 γ-rays. Circulating blood counts, histopathologic changes in the bone marrow, and plasma level of Flt-3L and transforming growth factor (TGF-β1) were monitored in the postirradiation period. Hematologic analysis revealed that the peripheral leukocyte counts were markedly increased in the hUCB-MSCs-treated group, whereas G-CSF-treated mice did not recover significantly. Moreover, differential counts showed that hUCB-MSC treatment has regenerative effects on white blood cells, lymphocytes, and monocytes compared with the irradiated group. Treatment with hUCB-MSCs or G-CSF significantly increased immunoreactivity of Ki-67 until 3 weeks after total body irradiation. However, at 3 weeks, the number of Ki-67 immunoreactive cells significantly increased in the hUCB-MSCs-treated group compared with the G-CSF-treated group. Furthermore, hUCB-MSC treatment significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGF-β1, whereas G-CSF treatment failed to decrease the plasma Flt-3L levels at 2 weeks after irradiation. Based on the differences in circulating blood cell reconstitution and cell density of bone marrow, the authors suggest that MSC treatment is superior to G-CSF treatment for hematopoietic reconstitution following sublethal dose radiation exposure.
authors: National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors: Sehwan
authors: S
authors: Shim
authors: Seung Bum
authors: SB
authors: Lee
authors: Jong-geol
authors: JG
authors: Lee
authors: Won-Suk
authors: WS
authors: Jang
authors: Sun-Joo
authors: SJ
authors: Lee
authors: Sunhoo
authors: S
authors: Park
authors: Seung-Sook
authors: SS
authors: Lee
mesh_terms: D054508:Acute Radiation Syndrome / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005720:Gamma Rays / Q000009:adverse effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007958:Leukocyte Count; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects; D051941:fms-Like Tyrosine Kinase 3 / Q000097:blood
chemical_list: D019394:Ki-67 Antigen; D053773:Transforming Growth Factor beta1; D016179:Granulocyte Colony-Stimulating Factor; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3