nach oben

Erschienen in:

01.01.2021 | Original Article

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

verfasst von: Masaki Iwasa, Sumie Fujii, Aya Fujishiro, Taira Maekawa, Akira Andoh, Akifumi Takaori-Kondo, Tatsuo Ichinohe, Yasuo Miura

Erschienen in: International Journal of Hematology | Ausgabe 5/2021

Einloggen, um Zugang zu erhalten

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.

Thomas ED, Clift RA, Hersman J, Sanders JE, Stewart P, Buckner CD, et al. Marrow transplantation for acute nonlymphoblastic leukemic in first remission using fractionated or single-dose irradiation. Int J Radiat Oncol Biol Phys. 1982;8:817–21. https://doi.org/10.1016/0360-3016(82)90083-9.CrossRefPubMed

Deeg HJ, Sullivan KM, Buckner CD, Storb R, Appelbaum FR, Clift RA, et al. 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;1:151–7.PubMed

Thomas ED, Buckner CD, Banaji M, Clift RA, Fefer A, Flournoy N, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977;49:511–33.CrossRefPubMed

Storb R, Gyurkocza B, Storer BE, Sorror ML, Blume K, Niederwieser D, et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2013;31:1530–8. https://doi.org/10.1200/jco.2012.45.0247.CrossRefPubMed

Majhail NS, Rizzo JD. Surviving the cure: long term followup of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2013;48:1145–51. https://doi.org/10.1038/bmt.2012.258.CrossRefPubMed

Bhatia S, Francisco L, Carter A, Sun CL, Baker KS, Gurney JG, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood. 2007;110:3784–92. https://doi.org/10.1182/blood-2007-03-082933.CrossRefPubMedPubMedCentral

Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010;466:829–34. https://doi.org/10.1038/nature09262.CrossRefPubMedPubMedCentral

Fekete N, Erle A, Amann EM, Fürst D, Rojewski MT, Langonné A, et al. Effect of high-dose irradiation on human bone-marrow-derived mesenchymal stromal cells. Tissue Eng Part C Methods. 2015;21:112–22. https://doi.org/10.1089/ten.tec.2013.0766.CrossRefPubMed

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

10.

Pelszynski MM, Moroff G, Luban NL, Taylor BJ, Quinones RR. Effect of gamma irradiation of red blood cell units on T-cell inactivation as assessed by limiting dilution analysis: implications for preventing transfusion-associated graft-versus-host disease. Blood. 1994;83:1683–9.CrossRefPubMed

11.

Preciado S, Muntión S, Rico A, Pérez-Romasanta LA, Ramos TL, Ortega R, et al. Mesenchymal stromal cell irradiation interferes with the adipogenic/osteogenic differentiation balance and improves their hematopoietic-supporting ability. Biol Blood Marrow Transplant. 2018;24:443–51. https://doi.org/10.1016/j.bbmt.2017.11.007.CrossRefPubMed

12.

Iwasa M, Miura Y, Fujishiro A, Fujii S, Sugino N, Yoshioka S, et al. 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;105:587–97. https://doi.org/10.1007/s12185-016-2169-x.CrossRefPubMed

13.

Fujii S, Miura Y, Fujishiro A, Shindo T, Shimazu Y, Hirai H, et al. 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. 2018;36:434–45. https://doi.org/10.1002/stem.2759.CrossRefPubMed

14.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7. https://doi.org/10.1080/14653240600855905.CrossRefPubMed

15.

Sugino N, Miura Y, Yao H, Iwasa M, Fujishiro A, Fujii S, et al. 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. 2016;469:823–9. https://doi.org/10.1016/j.bbrc.2015.12.061.CrossRefPubMed

16.

Yao H, Miura Y, Yoshioka S, Miura M, Hayashi Y, Tamura A, et al. Parathyroid hormone enhances hematopoietic expansion via upregulation of cadherin-11 in bone marrow mesenchymal stromal cells. Stem Cells. 2014;32:2245–55. https://doi.org/10.1002/stem.1701.CrossRefPubMed

17.

Ichii M, Oritani K, Yokota T, Schultz DC, Holter JL, Kanakura Y, et al. Stromal cell-free conditions favorable for human B lymphopoiesis in culture. J Immunol Methods. 2010;359:47–55. https://doi.org/10.1016/j.jim.2010.06.002.CrossRefPubMedPubMedCentral

18.

Alessio N, Del Gaudio S, Capasso S, Di Bernardo G, Cappabianca S, Cipollaro M, et al. Low-dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. Oncotarget. 2015;6:8155–66. https://doi.org/10.18632/oncotarget.2692.CrossRefPubMed

19.

Osipov AN, Pustovalova M, Grekhova A, Eremin P, Vorobyova N, Pulin A, et al. Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells. Oncotarget. 2015;6:27275–87. https://doi.org/10.18632/oncotarget.4739.CrossRefPubMedPubMedCentral

20.

Laurent A, Blasi F. Differential DNA damage signaling and apoptotic threshold correlate with mouse epiblast-specific hypersensitivity to radiation. Development. 2015;142:3675–85. https://doi.org/10.1242/dev.125708.CrossRefPubMed

21.

Tubbs A, Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer. Cell. 2017;168:644–56. https://doi.org/10.1016/j.cell.2017.01.002.CrossRefPubMedPubMedCentral

22.

Lomax M, Folkes L, O’Neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol (R Coll Radiol). 2013;25:578–85. https://doi.org/10.1016/j.cell.2017.01.002.CrossRef

23.

Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci USA. 2003;100:12871–6. https://doi.org/10.1073/pnas.2135498100.CrossRefPubMedPubMedCentral

24.

Dias S, Silva H Jr, Cumano A, Vieira P. Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors. J Exp Med. 2005;201:971–9. https://doi.org/10.1084/jem.20042393.CrossRefPubMedPubMedCentral

25.

Egawa T, Kawabata K, Kawamoto H, Amada K, Okamoto R, Fujii N, et al. The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity. 2001;15:323–34. https://doi.org/10.1016/s1074-7613(01)00185-6.CrossRefPubMed

26.

Zhou H, Choong P, McCarthy R, Chou S, Martin T, Ng KW. In situ hybridization to show sequential expression of osteoblast gene markers during bone formation in vivo. J Bone Miner Res. 1994;9:1489–99. https://doi.org/10.1002/jbmr.5650090922.CrossRefPubMed

27.

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755–64. https://doi.org/10.1016/s0092-8674(00)80258-5.CrossRefPubMed

28.

Golub EE, Boesze-Battaglia K. The role of alkaline phosphatase in mineralization. Curr Opin Orthop. 2007;18:444–8. https://doi.org/10.1097/bco.0b013e3282630851.CrossRef

29.

Cutler C, Ballen K. Reduced-intensity conditioning and umbilical cord blood transplantation in adults. Bone Marrow Transplant. 2009;44:667–71. https://doi.org/10.1038/bmt.2009.283.CrossRefPubMed

30.

Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M, et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood. 2007;109:1322–30. https://doi.org/10.1182/blood-2006-04-020172.CrossRefPubMed

31.

Muller-Sieburg CE, Cho RH, Karlsson L, Huang JF, Sieburg HB. Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood. 2004;103:4111–8. https://doi.org/10.1182/blood-2003-10-3448.CrossRefPubMed

32.

Velardi E, Tsai JJ, van den Brink MRM. T cell regeneration after immunological injury. Nat Rev Immunol. 2020. https://doi.org/10.1038/s41577-020-00457-z.CrossRefPubMedPubMedCentral

33.

Krampera M, Sartoris S, Liotta F, Pasini A, Angeli R, Cosmi L, et al. Immune regulation by mesenchymal stem cells derived from adult spleen and thymus. Stem Cells Dev. 2007;16:797–810. https://doi.org/10.1089/scd.2007.0024.CrossRefPubMed

34.

Patenaude J, Perreault C. Thymic mesenchymal cells have a distinct transcriptomic profile. J Immunol. 2016;196:4760–70. https://doi.org/10.4049/jimmunol.1502499.CrossRefPubMed

35.

Suniara RK, Jenkinson EJ, Owen JJ. An essential role for thymic mesenchyme in early T cell development. J Exp Med. 2000;191:1051–6. https://doi.org/10.1084/jem.191.6.1051.CrossRefPubMedPubMedCentral

Titel: Impact of 2 Gy γ-irradiation on the hallmark characteristics of human bone marrow-derived MSCs
verfasst von: Masaki Iwasa
Sumie Fujii
Aya Fujishiro
Taira Maekawa
Akira Andoh
Akifumi Takaori-Kondo
Tatsuo Ichinohe
Yasuo Miura
Publikationsdatum: 01.01.2021
Verlag: Springer Singapore
Erschienen in: International Journal of Hematology / Ausgabe 5/2021
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-020-03072-9

Springer Medizin

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

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2021

Latest trends in the incidence of Helicobacter pylori-uninfected gastric mucosa-associated lymphoid tissue lymphoma at the Cancer Institute Hospital, Japan

MPL exon 10 mutations other than canonical MPL W515L/K mutations identified by in-house MPL exon 10 direct sequencing in essential thrombocythemia

Current status and novel strategy of CML

Prevalence of and risk factors for urolithiasis in Croatian patients with hemophilia

Biopsy remains indispensable for evaluating bone marrow involvement in DLBCL patients despite the use of positron emission tomography

Prognostic impact of 18F-FDG PET/CT in patients with multiple myeloma presenting with renal impairment

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie