Skip to main content
Erschienen in: Annals of Hematology 4/2018

18.01.2018 | Original Article

Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells

verfasst von: Wen-Jyi Lo, Chiao-Lin Lin, Yu-Chien Chang, Li-Yuan Bai, Chen-Yuan Lin, Ji-An Liang, Long-Yuan Li, Ling-Min Chao, Chang-Fang Chiu, Chuan-Mu Chen, Su-Peng Yeh

Erschienen in: Annals of Hematology | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Total body irradiation (TBI) is frequently used in hematopoietic stem cell transplantation (HSCT) and is associated with many complications due to radiation injury to the normal cells, including normal stem cells. Nevertheless, the effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical to that used in TBI-conditioning HSCT. The characteristics, differentiation potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity of the irradiated BM-MSCs were then compared to the non-irradiated control. The irradiated and non-irradiated MSCs shared similar morphology, phenotype, and hematopoiesis-supporting function. However, irradiated MSCs showed much lower proliferative and differentiative potential. Irradiation also induced clonal cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo irradiation experiments, decreased proliferative and differentiative abilities and clonal cytogenetic abnormalities can also be found in MSCs isolated from transplant recipients who had received TBI-based conditioning previously. Thus, TBI used in HSCT drastically injury MSCs and may contribute to the development of some long-term complications associated with clonal cytogenetic abnormality and poor adipogenesis and osteogenesis after TBI.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
4.
6.
Zurück zum Zitat Wang BL, Sun W, Shi ZC, Lou JN, Zhang NF, Shi SH, Guo WS, Cheng LM, Ye LY, Zhang WJ, Li ZR (2008) Decreased proliferation of mesenchymal stem cells in corticosteroid-induced osteonecrosis of femoral head. Orthopedics 31(5):444PubMed Wang BL, Sun W, Shi ZC, Lou JN, Zhang NF, Shi SH, Guo WS, Cheng LM, Ye LY, Zhang WJ, Li ZR (2008) Decreased proliferation of mesenchymal stem cells in corticosteroid-induced osteonecrosis of femoral head. Orthopedics 31(5):444PubMed
10.
Zurück zum Zitat Onate B, Vilahur G, Camino-Lopez S, Diez-Caballero A, Ballesta-Lopez C, Ybarra J, Moscatiello F, Herrero J, Badimon L (2013) Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype. BMC Genomics 14(1):625. https://doi.org/10.1186/1471-2164-14-625 CrossRefPubMedPubMedCentral Onate B, Vilahur G, Camino-Lopez S, Diez-Caballero A, Ballesta-Lopez C, Ybarra J, Moscatiello F, Herrero J, Badimon L (2013) Stem cells isolated from adipose tissue of obese patients show changes in their transcriptomic profile that indicate loss in stemcellness and increased commitment to an adipocyte-like phenotype. BMC Genomics 14(1):625. https://​doi.​org/​10.​1186/​1471-2164-14-625 CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Mansilla E, Diaz Aquino V, Zambon D, Marin GH, Martire K, Roque G, Ichim T, Riordan NH, Patel A, Sturla F, Larsen G, Spretz R, Nunez L, Soratti C, Ibar R, van Leeuwen M, Tau JM, Drago H, Maceira A (2011) Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes? Stem Cells Int 2011:943216–943210. https://doi.org/10.4061/2011/943216 CrossRefPubMedPubMedCentral Mansilla E, Diaz Aquino V, Zambon D, Marin GH, Martire K, Roque G, Ichim T, Riordan NH, Patel A, Sturla F, Larsen G, Spretz R, Nunez L, Soratti C, Ibar R, van Leeuwen M, Tau JM, Drago H, Maceira A (2011) Could metabolic syndrome, lipodystrophy, and aging be mesenchymal stem cell exhaustion syndromes? Stem Cells Int 2011:943216–943210. https://​doi.​org/​10.​4061/​2011/​943216 CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D, van Pel M, Cleton-Jansen AM, Hogendoorn PC (2009) Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol 219(3):294–305. https://doi.org/10.1002/path.2603 CrossRefPubMed Mohseny AB, Szuhai K, Romeo S, Buddingh EP, Briaire-de Bruijn I, de Jong D, van Pel M, Cleton-Jansen AM, Hogendoorn PC (2009) Osteosarcoma originates from mesenchymal stem cells in consequence of aneuploidization and genomic loss of Cdkn2. J Pathol 219(3):294–305. https://​doi.​org/​10.​1002/​path.​2603 CrossRefPubMed
13.
Zurück zum Zitat Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25(2):371–379. https://doi.org/10.1634/stemcells.2005-0620 CrossRefPubMed Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR (2007) Sarcoma derived from cultured mesenchymal stem cells. Stem Cells 25(2):371–379. https://​doi.​org/​10.​1634/​stemcells.​2005-0620 CrossRefPubMed
14.
Zurück zum Zitat Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D, Maccario R, Villa R, Daidone MG, Zuffardi O, Locatelli F (2007) Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res 67(19):9142–9149. https://doi.org/10.1158/0008-5472.CAN-06-4690 CrossRefPubMed Bernardo ME, Zaffaroni N, Novara F, Cometa AM, Avanzini MA, Moretta A, Montagna D, Maccario R, Villa R, Daidone MG, Zuffardi O, Locatelli F (2007) Human bone marrow derived mesenchymal stem cells do not undergo transformation after long-term in vitro culture and do not exhibit telomere maintenance mechanisms. Cancer Res 67(19):9142–9149. https://​doi.​org/​10.​1158/​0008-5472.​CAN-06-4690 CrossRefPubMed
15.
Zurück zum Zitat Rosland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, Lonning PE, Bjerkvig R, Schichor C (2009) Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 69(13):5331–5339. https://doi.org/10.1158/0008-5472.CAN-08-4630 CrossRefPubMed Rosland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, Lonning PE, Bjerkvig R, Schichor C (2009) Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res 69(13):5331–5339. https://​doi.​org/​10.​1158/​0008-5472.​CAN-08-4630 CrossRefPubMed
16.
Zurück zum Zitat Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, Nielsen GP, Quade BJ, Chaber CJ, Schultz CP, Takeuchi O, Bronson RT, Crowley D, Korsmeyer SJ, Yoon SS, Hornicek FJ, Weissleder R, Jacks T (2007) A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 13(8):992–997. https://doi.org/10.1038/nm1602 CrossRefPubMed Kirsch DG, Dinulescu DM, Miller JB, Grimm J, Santiago PM, Young NP, Nielsen GP, Quade BJ, Chaber CJ, Schultz CP, Takeuchi O, Bronson RT, Crowley D, Korsmeyer SJ, Yoon SS, Hornicek FJ, Weissleder R, Jacks T (2007) A spatially and temporally restricted mouse model of soft tissue sarcoma. Nat Med 13(8):992–997. https://​doi.​org/​10.​1038/​nm1602 CrossRefPubMed
18.
Zurück zum Zitat Rajendran R, Abu E, Fadl A, Byrne CD (2013) Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation. Diabet Med 30(8):e239–e242. https://doi.org/10.1111/dme.12234 CrossRefPubMed Rajendran R, Abu E, Fadl A, Byrne CD (2013) Late effects of childhood cancer treatment: severe hypertriglyceridaemia, central obesity, non alcoholic fatty liver disease and diabetes as complications of childhood total body irradiation. Diabet Med 30(8):e239–e242. https://​doi.​org/​10.​1111/​dme.​12234 CrossRefPubMed
23.
Zurück zum Zitat Inamoto Y, Shah NN, Savani BN, Shaw BE, Abraham AA, Ahmed IA, Akpek G, Atsuta Y, Baker KS, Basak GW, Bitan M, DeFilipp Z, Gregory TK, Greinix HT, Hamadani M, Hamilton BK, Hayashi RJ, Jacobsohn DA, Kamble RT, Kasow KA, Khera N, Lazarus HM, Malone AK, Lupo-Stanghellini MT, Margossian SP, Muffly LS, Norkin M, Ramanathan M, Salooja N, Schoemans H, Wingard JR, Wirk B, Wood WA, Yong A, Duncan CN, Flowers ME, Majhail NS (2015) Secondary solid cancer screening following hematopoietic cell transplantation. Bone Marrow Transplant 50(8):1013–1023. https://doi.org/10.1038/bmt.2015.63 CrossRefPubMedPubMedCentral Inamoto Y, Shah NN, Savani BN, Shaw BE, Abraham AA, Ahmed IA, Akpek G, Atsuta Y, Baker KS, Basak GW, Bitan M, DeFilipp Z, Gregory TK, Greinix HT, Hamadani M, Hamilton BK, Hayashi RJ, Jacobsohn DA, Kamble RT, Kasow KA, Khera N, Lazarus HM, Malone AK, Lupo-Stanghellini MT, Margossian SP, Muffly LS, Norkin M, Ramanathan M, Salooja N, Schoemans H, Wingard JR, Wirk B, Wood WA, Yong A, Duncan CN, Flowers ME, Majhail NS (2015) Secondary solid cancer screening following hematopoietic cell transplantation. Bone Marrow Transplant 50(8):1013–1023. https://​doi.​org/​10.​1038/​bmt.​2015.​63 CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat in 't Anker PS, Noort WA, Scherjon SA, Kleijburg-van der Keur C, Kruisselbrink AB, van Bezooijen RL, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE (2003) Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 88(8):845–852PubMed in 't Anker PS, Noort WA, Scherjon SA, Kleijburg-van der Keur C, Kruisselbrink AB, van Bezooijen RL, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE (2003) Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica 88(8):845–852PubMed
28.
Zurück zum Zitat International Standing Committee on Human Cytogenetic Nomenclature, Shaffer LG, Slovak ML, Campbell LJ (2009) ISCN 2009: an international system for human cytogenetic nomenclature (2009). Karger, Basel; Unionville, CT International Standing Committee on Human Cytogenetic Nomenclature, Shaffer LG, Slovak ML, Campbell LJ (2009) ISCN 2009: an international system for human cytogenetic nomenclature (2009). Karger, Basel; Unionville, CT
29.
Zurück zum Zitat Novitzky N, Mohamed R (1995) Alterations in both the hematopoietic microenvironment and the progenitor cell population follow the recovery from myeloablative therapy and bone marrow transplantation. Exp Hematol 23(14):1661–1666PubMed Novitzky N, Mohamed R (1995) Alterations in both the hematopoietic microenvironment and the progenitor cell population follow the recovery from myeloablative therapy and bone marrow transplantation. Exp Hematol 23(14):1661–1666PubMed
30.
Zurück zum Zitat Laver J, Ebell W, Castro-Malaspina H (1986) Radiobiological properties of the human hematopoietic microenvironment: contrasting sensitivities of proliferative capacity and hematopoietic function to in vitro irradiation. Blood 67(4):1090–1097PubMed Laver J, Ebell W, Castro-Malaspina H (1986) Radiobiological properties of the human hematopoietic microenvironment: contrasting sensitivities of proliferative capacity and hematopoietic function to in vitro irradiation. Blood 67(4):1090–1097PubMed
32.
Zurück zum Zitat Ikeda S, Hachisu R, Yamaguchi A, Gao YH, Okano T (2000) Radiation retards muscle differentiation but does not affect osteoblastic differentiation induced by bone morphogenetic protein-2 in C2C12 myoblasts. Int J Radiat Biol 76(3):403–411CrossRefPubMed Ikeda S, Hachisu R, Yamaguchi A, Gao YH, Okano T (2000) Radiation retards muscle differentiation but does not affect osteoblastic differentiation induced by bone morphogenetic protein-2 in C2C12 myoblasts. Int J Radiat Biol 76(3):403–411CrossRefPubMed
33.
Zurück zum Zitat Pohl F, Hassel S, Nohe A, Flentje M, Knaus P, Sebald W, Koelbl O (2003) Radiation-induced suppression of the Bmp2 signal transduction pathway in the pluripotent mesenchymal cell line C2C12: an in vitro model for prevention of heterotopic ossification by radiotherapy. Radiat Res 159(3):345–350. Pohl F, Hassel S, Nohe A, Flentje M, Knaus P, Sebald W, Koelbl O (2003) Radiation-induced suppression of the Bmp2 signal transduction pathway in the pluripotent mesenchymal cell line C2C12: an in vitro model for prevention of heterotopic ossification by radiotherapy. Radiat Res 159(3):345–350.
35.
Zurück zum Zitat Baker KS, Ness KK, Steinberger J, Carter A, Francisco L, Burns LJ, Sklar C, Forman S, Weisdorf D, Gurney JG, Bhatia S (2007) Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood 109(4):1765–1772. https://doi.org/10.1182/blood-2006-05-022335 CrossRefPubMed Baker KS, Ness KK, Steinberger J, Carter A, Francisco L, Burns LJ, Sklar C, Forman S, Weisdorf D, Gurney JG, Bhatia S (2007) Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood 109(4):1765–1772. https://​doi.​org/​10.​1182/​blood-2006-05-022335 CrossRefPubMed
41.
Zurück zum Zitat Yao S, Smiley SL, West K, Lamonica D, Battiwalla M, McCarthy PL Jr, Hahn T (2010) Accelerated bone mineral density loss occurs with similar incidence and severity, but with different risk factors, after autologous versus allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 16(8):1130–1137. https://doi.org/10.1016/j.bbmt.2010.02.017 CrossRefPubMed Yao S, Smiley SL, West K, Lamonica D, Battiwalla M, McCarthy PL Jr, Hahn T (2010) Accelerated bone mineral density loss occurs with similar incidence and severity, but with different risk factors, after autologous versus allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 16(8):1130–1137. https://​doi.​org/​10.​1016/​j.​bbmt.​2010.​02.​017 CrossRefPubMed
43.
Zurück zum Zitat Dai QY, Souillet G, Bertrand Y, Galambrun C, Bleyzac N, Manel AM, Bruno B, Souillet AL, Homole E, Pages MP, Berlier P, David M, Berthier JC, Massenavette B, Contamin B, Philippe N (2004) Antileukemic and long-term effects of two regimens with or without TBI in allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia. Bone Marrow Transplant 34(8):667–673. https://doi.org/10.1038/sj.bmt.1704605 CrossRefPubMed Dai QY, Souillet G, Bertrand Y, Galambrun C, Bleyzac N, Manel AM, Bruno B, Souillet AL, Homole E, Pages MP, Berlier P, David M, Berthier JC, Massenavette B, Contamin B, Philippe N (2004) Antileukemic and long-term effects of two regimens with or without TBI in allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia. Bone Marrow Transplant 34(8):667–673. https://​doi.​org/​10.​1038/​sj.​bmt.​1704605 CrossRefPubMed
44.
Zurück zum Zitat Olshan JS, Willi SM, Gruccio D, Moshang T Jr (1993) Growth hormone function and treatment following bone marrow transplant for neuroblastoma. Bone Marrow Transplant 12(4):381–385PubMed Olshan JS, Willi SM, Gruccio D, Moshang T Jr (1993) Growth hormone function and treatment following bone marrow transplant for neuroblastoma. Bone Marrow Transplant 12(4):381–385PubMed
Metadaten
Titel
Total body irradiation tremendously impair the proliferation, differentiation and chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells
verfasst von
Wen-Jyi Lo
Chiao-Lin Lin
Yu-Chien Chang
Li-Yuan Bai
Chen-Yuan Lin
Ji-An Liang
Long-Yuan Li
Ling-Min Chao
Chang-Fang Chiu
Chuan-Mu Chen
Su-Peng Yeh
Publikationsdatum
18.01.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 4/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-018-3231-y

Weitere Artikel der Ausgabe 4/2018

Annals of Hematology 4/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.