TY - JOUR
T1 - Impact of 2 Gy γ-irradiation on the hallmark characteristics of human bone marrow-derived MSCs
AU - Iwasa, Masaki
AU - Fujii, Sumie
AU - Fujishiro, Aya
AU - Maekawa, Taira
AU - Andoh, Akira
AU - Takaori-Kondo, Akifumi
AU - Ichinohe, Tatsuo
AU - Miura, Yasuo
N1 - Funding Information:
This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (#18K08323 to Y.M., #19K17856 to S.F.) and by the Japanese Society of Hematology Research Grant (Y.M. and S.F.).
Funding Information:
T. Ichinohe has received research funding from FUJIFILM Wako Chemicals, Repertoire Genesis Inc., and Takara Bio Inc.
Publisher Copyright:
© 2021, Japanese Society of Hematology.
PY - 2021/5
Y1 - 2021/5
N2 - Two gray γ-irradiation is a widely employed basic module for total body irradiation (TBI) in allogeneic hematopoietic cell transplantation (HCT). The effects of γ-irradiation on hematopoietic and immune cells have been well investigated, but its effects on the bone marrow microenvironment (BMM) are unknown. Given the crucial contribution of mesenchymal/stromal stem cells (MSCs) in the BMM to hematopoiesis and osteogenesis, we investigated whether γ-irradiation affects the hallmark characteristics of human bone marrow-derived MSCs (BM-MSCs). Expansion of 2 Gy γ-irradiated BM-MSCs was delayed but eventually recovered. Colony formation and osteogenic, adipogenic, and chondrogenic differentiation capabilities of these cells were extensively suppressed. Irradiation of BM-MSCs did not affect the expansion of CD34 + hematopoietic stem and progenitor cells or production of CD11b + mature myeloid cells in co-cultures. However, it reduced production of CD19 + B-cells, as well as expression of CXCL12 and interleukin-7, which are essential for B-cell lymphopoiesis, in 2 Gy γ-irradiated BM-MSCs. Collectively, colony formation, osteogenic differentiation, and B-cell lymphopoiesis-supportive capabilities of γ-irradiated BM-MSCs were reduced. These effects may predispose survivors receiving HCT with TBI to defective bone formation and a perturbed humoral immune response.
AB - Two gray γ-irradiation is a widely employed basic module for total body irradiation (TBI) in allogeneic hematopoietic cell transplantation (HCT). The effects of γ-irradiation on hematopoietic and immune cells have been well investigated, but its effects on the bone marrow microenvironment (BMM) are unknown. Given the crucial contribution of mesenchymal/stromal stem cells (MSCs) in the BMM to hematopoiesis and osteogenesis, we investigated whether γ-irradiation affects the hallmark characteristics of human bone marrow-derived MSCs (BM-MSCs). Expansion of 2 Gy γ-irradiated BM-MSCs was delayed but eventually recovered. Colony formation and osteogenic, adipogenic, and chondrogenic differentiation capabilities of these cells were extensively suppressed. Irradiation of BM-MSCs did not affect the expansion of CD34 + hematopoietic stem and progenitor cells or production of CD11b + mature myeloid cells in co-cultures. However, it reduced production of CD19 + B-cells, as well as expression of CXCL12 and interleukin-7, which are essential for B-cell lymphopoiesis, in 2 Gy γ-irradiated BM-MSCs. Collectively, colony formation, osteogenic differentiation, and B-cell lymphopoiesis-supportive capabilities of γ-irradiated BM-MSCs were reduced. These effects may predispose survivors receiving HCT with TBI to defective bone formation and a perturbed humoral immune response.
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U2 - 10.1007/s12185-020-03072-9
DO - 10.1007/s12185-020-03072-9
M3 - Article
AN - SCOPUS:85098520183
VL - 113
SP - 703
EP - 711
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 5
ER -