Abstract
Bone marrow cells of mesenchymal origin play an important role in adaptation of physiological systems to space flight. Hematopoiesis, immunity, and homeostasis of bone tissue depend on their functional activity. An investigation that was carried out in the framework of the Bion and Bion-M programs showed a decrease of the number of rat bone marrow hematopoietic progenitors and the inhibition of lympho- and erythropoiesis when the granulocyte-macrophage linage was activated. A negative influence on nonhematopoietic bone marrow cells was also revealed. The pathogenetic influence of radiation and microgravity on the bone marrow progenitor cells has remained unclear so far. The goal of this research was to study the effect of a 30-day unloading and 6 days of γ-irradiation on rat bone marrow progenitor cells. The study was conducted on male rats of four groups: vivarium control (VC), hindlimb unloading (HU), irradiation (IR), and combined action (HU + IR). The following parameters have been examined: the number of bone marrow mononuclear cells, proliferative activity of marrow mononuclear cells, immunophenotype, number of hematopoietic CFU and CFU-f, and differentiation potency of hematopoietic and stromal bone marrow precursors. It was found that the cellularity and proliferation activity of rat bone marrow cells did not change under simulation of space flight. The number of CFU-f was decreased. Irradiation was accompanied by an increase in the hematopoietic cell share among total bone marrow mononuclear cells, while their activity was attenuated. The osteopotential of the stromal precursors was unchanged. Adipogenic differentiation was stimulated with irradiation. The functional activity of bone marrow progenitor cells was restored after 2 weeks of recovery. Thus, 30-day simulation of space flight factors negatively affected the morphofunctional properties of rat bone marrow progenitor cells. These effects were reversible upon 2 weeks of recovery.
Similar content being viewed by others
Abbreviations
- HSC:
-
hematopoietic stem cell
- BM:
-
bone marrow
- SF:
-
space flight
- FITC:
-
fluorescein isothiocyanate
- PE:
-
phycoerythrin
- PD:
-
population doubling
References
Akleev, AV., Reaction of tissues to chronic exposure to ionizing radiation, Radiats. Biol. Radioekol., 2009, vol. 49, no. 31, pp. 5–20.
Allebban, Z., Gibson, L.A., Lange, R.D., Jago, T.L., Strickland, K.M., Johnson, D.L., and Ichiki, A.T., Effects of space flight on rat erythroid parameters, J. Appl. Physiol., 1996, vol. 81, pp. 117–122.
Andreeva, E.R., Goncharova, E.A., Gornostaeva, A.N., Grigor’eva, O.V., and Buravkova, L.B., Bone marrow mononuclar cells from murine tibia after space flight on biosatellite “Bion-M1,” Aviakosm. Ekol. Med., 2014, vol. 48, no. 2, pp. 5–11.
Anjos-Afonso, F., Siapati, E.K., and Bonnet, D., In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions, J. Cell Sci., 2004, vol. 117, pp. 5655–5664.
Anokhina, E.B. and Buravkova, L.B., Heterogeneity of stromal precursor cells isolated from rat bone marrow, Tsitologiia, 2007, vol. 49, no. 1, pp. 40–47.
Blaber, E.A., Dvorochkin, N., Lee, C.Alwood, J.S., Yousuf, R., Piero, Pianetta, Globus, R.K., Burns, B.P., and Almeida, E.A.C., Microgravity induces pelvic bone loss through osteoclastic activity, osteocytic osteolysis, and osteoblastic cell cycle inhibition by CDKN1a/p21, PLoS One, 2013, vol. 8, p. e61372.
Buravkova, L.B., Gershovich, P.M., Gershovich, J.G., and Grigor’ev, A.I., Mechanisms of gravitational sensitivity of osteogenic precursor cells, Acta Naturae, 2010, vol. 2, no. 1, pp. 28–36.
Chowdhury, P., Akel, N., Jamshidi-Parsian, A., Gaddy, D., Griffin, R.J., Yadlapalli, J.S.K, and Dobretsov, M., Degenerative tissue responses to space-like radiation doses in a rodent model of simulated microgravity, Ann. Clin. Lab. Sci., 2016, vol. 46, pp. 190–197.
Delaine-Smith, R.M. and Reilly, G.D., Mesenchymal stem cell responses to mechanical stimuli, Muscl. Ligam. Tendon. J., 2012, vol. 2, pp. 169–180.
Domaratskaya, E.I., Michurina, T.V., Bueverova, E.I., Payushina, O.I., Butorina, N.N., Khrushchov, N.G., and Starostin, V.I., Studies on clonogenic hemopoietic cells of vertebrate in space: problems and perspectives, Adv. Space Res., 2002, vol. 30, pp. 771–776.
Domaratskaya, E.I., Starostin, V.I., Tsetlin, V.V., Bueverova, E.I., and Khrushchev, N.G., Effects of ten day long exposure to γ-irradiation at low doses on bone marrow cells in mice, Radiats. Biol. Radioekol., 2003, vol. 43, no. 2, pp. 213–215.
Durnova, G.N., Kaplansky, A.S. Ilyina-Kakueva, E.I., and Sakharova, Z.F., Histomorphometric analysis bone of rat exposed onboard “Kosmos-1887" biosatellite, Kosm. Biol. Aviakosm. Med., 1990, vol. 24, no. 5, pp. 42–45.
Gazenko, O.G., Ilyin, E.A., Savina, E.A., Serova, L.V., Kaplansky, A.S., Oganov, V.S., Popova, I.A., Smirnov, K.V., and Konstantinova, I.V., The experiment on rats exposed aboard “Kosmos-1667 biosatellite,” Kosm. Aviakosm. Med., 1987, vol. 21, no. 4, pp. 9–16.
Gershovich, P.M., Gershovich, J.G., and Buravkova, L.B., The role of multipotent mesenchymal stromal cells in adap-tation of cells of osteogenic differon to microgravity, Ross. Fiziol. Zh. im. I.M. Sechenova, 2004, vol. 96, no. 4, pp. 406–418.
Globus, R.K. and Morey-Holton, E.R., Hindlimb unloading: rodent analog for microgravity, J. Appl. Physiol., 2016, vol. 1985, no. 120, pp. 1196–1206.
Green, D.E. and Rubin, C.T., Consequences of irradiation on bone and marrow phenotypes, and its relation to disruption of hematopoietic precursors, Bone, 2014, vol. 63, pp. 87–94.
Grigor’ev, A.I. and Ilyin, E.A., Animals in the space, Vestnik Ross. Akad. Nauk, 2007, vol. 77, no. 11, pp. 963–986.
Grigoriev, Yu.G., Druzhinin, Yu.P., Verigo, V.V., and Ilyin, E.A., Main tasks and results of the radiobiological experiment aboard the Cosmos-690 biosatellite, Kosm. Aviakosm. Med., 1977, vol. 5, pp. 58–66.
Ichiki, A.T., Gibson, L.A., Jago, T.L., Strickland, K.M., Johnson, D.L., Lange, R.D., and Allebban, Z., Effects of space flight on rat peripheral blood leukocytes and bone marrow progenitor cells, J. Leukocyte Biol., 1996, vol. 60, pp. 37–43.
Jee, W.S., Wronski, T.J., Morey, E.R., and Kimmel, D.B., Effects of space flight on trabecular bone in rats, Am. J. Physiol., 1983, vol. 244, pp. 310–314.
Kalandrova, M.P., Rodina, G.P. and Serova, L.V., Peculiarities of physiological and reparative regeneration of the bone marrow of rats exposed to biosatellites “Kosmos-605 and 690,” Probl. Gematol. Pereliv. Krovi, 1981, vol. 26, no. 12, pp. 26–30.
Lesnyak, A., Sonnenfeld, G., Avery, L., Konstantinova, I., Rykova, M., Meshkov, D., and Orlova, T., Effect of SLS-2 space flight on immunologic parameters of rats, J. Appl. Physiol., 1996, vol. 81, pp. 178–182.
Markina, E.A., Bobyleva, P.I., Andrianova, I.V., Andreeva, E.R., and Buravkova, L.B., Profile of the marrow-derived stromal precursors population in C57BL/6N mice flown on biosatellite Bion-M1, Aviakosm. Ekol. Med., 2015, vol. 49, no. 6, pp. 41–48.
Meirelles Lda, S. and Nardi, N.B., Murine marrow-derived mesenchymal stem cell: isolation, in vitro expansion, and characterization, Br. J. Haematol., 2003, vol. 123, pp. 702–711.
Morey-Holton, E.R. and Globus, R.K., Hindlimb unloading rodent model: technical aspects, J. Appl. Physiol., 2002, vol. 92, pp. 1367–1377.
Morey-Holton, E.R., Globus, R.K., Kaplansky, A., and Durnova, G., The hindlimb unloading rat model: overview, technique update and comparasion with space flight data, Adv. Space Biol. Med., 2005, vol. 10, pp. 7–40.
Nabavi, N, Khandani, A, Camirand, A, and Harrison, R.E., Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion, Bone, 2011, vol. 49, pp. 965–974.
Pandey, R., Shancar, B.S., Sharma, D., and Sainis, K.B., Low dose radiation induced immunomodulation: effect on macrophages and CD8+ T cells, Int. J. Radiat. Biol., 2005, vol. 81, pp. 801–812.
Pani, G., Verslegers, M., Quintens, R., Samari, N., de Saint-Georges, L., van Oostveldt, P., Baatout, S., and Benotmane, M.A., Combined exposure to simulated microgravity and acute or chronic radiation reduces neuronal network integrity and survival, PLoS One, 2016, vol. 11, p. e0155260.
Payushina, O.V., Bueverova, E.I., Satdykova, G.P. Starostin, V.I., Domaratskaya, E.I., and Khrushchev, N.G., Comparative investigation of mesenchymal stem cells isolated from the bone marrow and fetal liver of mouse and rat, Biol. Bull. (Moscow), 2004, vol. 31, no. 6, pp. 546–551.
Phinney, D.G., Kopen, G, Isaacson, R.L., and Procop, D.G., Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation, J. Cell Biochem., 1999, vol. 72, pp. 570–585.
Portugalov, V.V., Savina, E.A., Kaplansky, A.S., Yakovleva, V.I., Durnova, G.N., Pankova, A.S., Shvets, V.N., Alekseyev, E.I., and Katunyan, P.I., Discussion of the combined effect of weightlessness and ionizing radiation on the mammalian body: morphological data, Aviat. Space Environ. Med., 1977, vol. 48, pp. 33–36.
Rogacheva, I.V., Stupakov, G.N., Volozhin, A.I., Pavlova, M.N., and Polyakov, A.N., Characteristics of bone tissue of rats after flight biosatellite “Kosmos-1129,” Kosm. Biol. Aviakosm. Med., 1984, vol. 18, no. 5, pp. 39–44.
Shahnazari, M., Kurimoto, P., Boudignon, B.M., Orwoll, B.E., Bikle, D.D., and Halloran, B.P., Simulated space flight produces a rapid and sustained loss of osteoprogenitors and an acute but transitory rise of osteoclast precursors in two genetic strains of mice, Am. J. Physiol. Endocrinol. Metab., 2012, vol. 303, pp. 1354–1362.
Shtemberg, A.S., The combined action of head-down tilt hypodynamia and gamma irradiation on higher nervous activity in rats, Aviakosm. Ekol. Med., 1992, vol. 26, no. 4, pp. 64–67.
Shtemberg, A.S., Problems of experimental studies of combined action of space flight factors on functions of the animal organism, Ross. Fiziol. Zh. im. I.M. Sechenova, 2014, vol. 100, no. 10, pp. 1152–1168.
Shtemberg, A.S., Lebedeva-Georgievskaya, K.V., Matveeva, M.I., Kudrin, V.S., Narkevich, V.B., Klodt, P.M., and Bazyan, A.S., Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats, Biol. Bull. (Moscow), 2014, vol. 41, no. 2, pp. 161–167.
Shvetz, V.N. and Krivenkova, N.P., Morphology of bone marrow cells of rats onboard “Cosmos-605" biosatellite, Kosm. Biol. Aviakosm. Med., 1977, vol. 4, pp. 12–16.
Shvetz, V.N., Vacek, A., Kozinetz, G.I. Britvan, I., Korol’kov, V.I., and Chelnaya, N.A., Hematopoiesis state in rats after weightlessness, Kosm. Biol. Aviakosm. Med., 1984, vol. 11, no. 4, pp. 12–16.
Smith, S.M., Heer, M., Shackelford, L.C., Sibonga, J.D., Spatz, J., Pietrzyk, R.A., Hudson, E.K., and Zwart, S.R., Bone metabolism and renal stone risk during international space station missions, Bone, 2015, vol. 81, pp. 712–720.
Sotnezova, E.V., Markina, E.A., Andreeva, E.R., and Buravkova, L.B., Myeloid precursors in the bone marrow of mice after a 30-day space mission on a Bion-M1 biosatellite, Bull. Exp. Biol. Med., 2016, vol. 162, no. 4, pp. 496–500.
Vacek, A., Tkadlecek, L., Shvets, V.N., Bartonickova, A., Viklika, S., Rotkovsky, D., Serova, L.V., and Michurina, T.V., Space flight effect on haemopoietic stemcells of the bone marrow of rats, Cell Tissue Kinetics, 1982, vol. 15, pp. 643–649.
Vacek, A., Serova, L.V., Rotkovsky, D., Mitchurina, T.V., Damaratskaya, E.I., Bartonickova, A., Pryanishnikova, O.D., and Khrushchov, N.G., Changes in the number of haemopoietic stem cells (CFUs) in bone marrow and spleens of pregnant rats after a short space flight onboard the Cosmos-1514 biosatellite, Folia Biol. (Praha), 1985, vol. 31, pp. 61–65.
Vacek, A., Bueverova, E.I., Michurina, T.V., Rotkovsky, D., Serova, L.V., and Bartonickova, A., Desrease in the number of progenitors of fibroblast (CFU(f)) in bone marrow of rats after a 14-days flight onboard the Cosmos-2044 biosatellite, Folia Biol., 1990, vol. 36, pp. 194–197.
Vacek, A., Michurina, T.V., Serova, L.V., Rotkovsky, D., and Bartonickova, A., Decrease in the number of progenitors of erythrocytes (BFUe, CFUe), granulocytes and macrophages (GM-CFC) in bone marrow of rats after a 14-days flight onboard the Cosmos-2044 biosatellite, Folia Biol., 1991, vol. 37, pp. 35–41.
Wronski, T.J., and Morey, E.R., Effect of space flight on periosteal bone formation in rats, Am. J. Physiol., 1983, vol. 244, pp. 305–309.
Zhu, H., Wang, H., and Liu, Z., Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: a review, Int. J. Occup. Med. Environ. Health, 2015, vol. 28, pp. 793–802.
Author information
Authors and Affiliations
Corresponding author
Additional information
Original Russian Text © E.A. Markina, V.S. Kokhan, M.P. Roe, I.V. Andrianova, A.S. Shtemberg, L.B. Buravkova, 2017, published in Tsitologiya, 2017, Vol. 59, No. 12, pp. 486–500.
Rights and permissions
About this article
Cite this article
Markina, E.A., Kokhan, V.S., Roe, M.P. et al. The Effects of Radiation and Hindlimb Unloading on Rat Bone Marrow Progenitor Cells. Cell Tiss. Biol. 12, 183–196 (2018). https://doi.org/10.1134/S1990519X18030069
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990519X18030069