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Impact of 2 Gy γ-irradiation on the hallmark characteristics of human bone marrow-derived MSCs

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Abstract

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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Acknowledgements

We thank Ms. Yoko Nakagawa for excellent technical assistance.

Funding

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.).

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Authors and Affiliations

  1. Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Masaki Iwasa, Sumie Fujii, Aya Fujishiro, Taira Maekawa & Yasuo Miura

  2. Division of Gastroenterology and Hematology, Department of Medicine, Shiga University of Medical Science, Setatsukinowacho, Otsu, Shiga, 520-2192, Japan

    Masaki Iwasa, Aya Fujishiro & Akira Andoh

  3. Department of Hematology/Oncology, Kyoto University Graduate School for Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Sumie Fujii, Akifumi Takaori-Kondo & Yasuo Miura

  4. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734-8553, Japan

    Tatsuo Ichinohe & Yasuo Miura

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  1. Masaki Iwasa
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Correspondence to Masaki Iwasa.

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T. Ichinohe has received research funding from FUJIFILM Wako Chemicals, Repertoire Genesis Inc., and Takara Bio Inc.

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Iwasa, M., Fujii, S., Fujishiro, A. et al. Impact of 2 Gy γ-irradiation on the hallmark characteristics of human bone marrow-derived MSCs. Int J Hematol 113, 703–711 (2021). https://doi.org/10.1007/s12185-020-03072-9

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