Impact of 2 Gy γ-irradiation on the Hallmark Characteristics of Human Bone Marrow-derived MSCs

Overview

Journal Int J Hematol

Specialty Hematology

Date 2021 Jan 2

PMID 33386593

Citations 2

Authors

Masaki Iwasa

Sumie Fujii

Aya Fujishiro

Taira Maekawa

Akira Andoh

Akifumi Takaori-Kondo

Tatsuo Ichinohe

Yasuo Miura

Affiliations

Soon will be listed here.

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.

Citing Articles

Cell-based and extracellular vesicle-based MSC therapies for acute radiation syndrome affecting organ systems.

Miura Y, Fujii S, Ichinohe T J Radiat Res. 2024; 65(Supplement_1):i80-i87.

PMID: 39679884 PMC: 11647929. DOI: 10.1093/jrr/rrae009.

Lenalidomide and pomalidomide modulate hematopoietic cell expansion and differentiation in the presence of MSC.

Fujii S, Miura Y Int J Hematol. 2024; 120(3):278-289.

PMID: 38995485 PMC: 11362235. DOI: 10.1007/s12185-024-03815-y.

References

Thomas E, Clift R, Hersman J, Sanders J, Stewart P, Buckner C . Marrow transplantation for acute nonlymphoblastic leukemic in first remission using fractionated or single-dose irradiation. Int J Radiat Oncol Biol Phys. 1982; 8(5):817-21. DOI: 10.1016/0360-3016(82)90083-9. View

Deeg H, Sullivan K, Buckner C, Storb R, Appelbaum F, Clift R . Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation. Bone Marrow Transplant. 1986; 1(2):151-7. View

Storb R, Gyurkocza B, Storer B, Sorror M, Blume K, Niederwieser D . Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2013; 31(12):1530-8. PMC: 3625710. DOI: 10.1200/JCO.2012.45.0247. View

Majhail N, Rizzo J . Surviving the cure: long term followup of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2013; 48(9):1145-51. DOI: 10.1038/bmt.2012.258. View

Bhatia S, Francisco L, Carter A, Sun C, Baker K, Gurney J . Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood. 2007; 110(10):3784-92. PMC: 2077324. DOI: 10.1182/blood-2007-03-082933. View

Mendez-Ferrer S, Michurina T, Ferraro F, Mazloom A, MacArthur B, Lira S . Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010; 466(7308):829-34. PMC: 3146551. DOI: 10.1038/nature09262. View

Fekete N, Erle A, Amann E, Furst D, Rojewski M, Langonne A . Effect of high-dose irradiation on human bone-marrow-derived mesenchymal stromal cells. Tissue Eng Part C Methods. 2014; 21(2):112-22. PMC: 4313408. DOI: 10.1089/ten.TEC.2013.0766. View

Fujishiro A, Miura Y, Iwasa M, Fujii S, Sugino N, Andoh A . Effects of acute exposure to low-dose radiation on the characteristics of human bone marrow mesenchymal stromal/stem cells. Inflamm Regen. 2017; 37:19. PMC: 5725824. DOI: 10.1186/s41232-017-0049-2. View

Preciado S, Muntion S, Rico A, Perez-Romasanta L, Ramos T, Ortega R . Mesenchymal Stromal Cell Irradiation Interferes with the Adipogenic/Osteogenic Differentiation Balance and Improves Their Hematopoietic-Supporting Ability. Biol Blood Marrow Transplant. 2017; 24(3):443-451. DOI: 10.1016/j.bbmt.2017.11.007. View

10.

Iwasa M, Miura Y, Fujishiro A, Fujii S, Sugino N, Yoshioka S . Bortezomib interferes with adhesion of B cell precursor acute lymphoblastic leukemia cells through SPARC up-regulation in human bone marrow mesenchymal stromal/stem cells. Int J Hematol. 2017; 105(5):587-597. DOI: 10.1007/s12185-016-2169-x. View

11.

Fujii S, Miura Y, Fujishiro A, Shindo T, Shimazu Y, Hirai H . Graft-Versus-Host Disease Amelioration by Human Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Is Associated with Peripheral Preservation of Naive T Cell Populations. Stem Cells. 2017; 36(3):434-445. DOI: 10.1002/stem.2759. View

12.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

13.

Sugino N, Miura Y, Yao H, Iwasa M, Fujishiro A, Fujii S . Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles. Biochem Biophys Res Commun. 2015; 469(4):823-9. DOI: 10.1016/j.bbrc.2015.12.061. View

14.

Yao H, Miura Y, Yoshioka S, Miura M, Hayashi Y, Tamura A . Parathyroid hormone enhances hematopoietic expansion via upregulation of cadherin-11 in bone marrow mesenchymal stromal cells. Stem Cells. 2014; 32(8):2245-55. DOI: 10.1002/stem.1701. View

15.

Ichii M, Oritani K, Yokota T, Schultz D, Holter J, Kanakura Y . Stromal cell-free conditions favorable for human B lymphopoiesis in culture. J Immunol Methods. 2010; 359(1-2):47-55. PMC: 2902975. DOI: 10.1016/j.jim.2010.06.002. View

16.

Alessio N, Gaudio S, Capasso S, Di Bernardo G, Cappabianca S, Cipollaro M . Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. Oncotarget. 2014; 6(10):8155-66. PMC: 4480742. DOI: 10.18632/oncotarget.2692. View

17.

Osipov A, Pustovalova M, Grekhova A, Eremin P, Vorobyova N, Pulin A . Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells. Oncotarget. 2015; 6(29):27275-87. PMC: 4694989. DOI: 10.18632/oncotarget.4739. View

18.

Laurent A, Blasi F . Differential DNA damage signalling and apoptotic threshold correlate with mouse epiblast-specific hypersensitivity to radiation. Development. 2015; 142(21):3675-85. DOI: 10.1242/dev.125708. View

19.

Tubbs A, Nussenzweig A . Endogenous DNA Damage as a Source of Genomic Instability in Cancer. Cell. 2017; 168(4):644-656. PMC: 6591730. DOI: 10.1016/j.cell.2017.01.002. View

20.

Vilenchik M, Knudson A . Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci U S A. 2003; 100(22):12871-6. PMC: 240711. DOI: 10.1073/pnas.2135498100. View