Low Intensity Vibrations Augment Mesenchymal Stem Cell Proliferation and Differentiation Capacity during in vitro Expansion.
Actin Cytoskeleton
/ metabolism
Adipogenesis
Animals
Cell Differentiation
Cell Proliferation
Cells, Cultured
Cellular Senescence
Male
Mechanotransduction, Cellular
/ physiology
Mesenchymal Stem Cells
/ physiology
Mice
Mice, Inbred C57BL
Osteogenesis
Vibration
/ adverse effects
beta-Galactosidase
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 06 2020
10 06 2020
Historique:
received:
27
11
2019
accepted:
13
05
2020
entrez:
12
6
2020
pubmed:
12
6
2020
medline:
15
12
2020
Statut:
epublish
Résumé
A primary component of exercise, mechanical signals, when applied in the form of low intensity vibration (LIV), increases mesenchymal stem cell (MSC) osteogenesis and proliferation. While it is generally accepted that exercise effectively combats the deleterious effects of aging in the musculoskeletal system, how long-term exercise affects stem cell aging, which is typified by reduced proliferative and differentiative capacity, is not well explored. As a first step in understanding the effect of long-term application of mechanical signals on stem cell function, we investigated the effect of LIV during in vitro expansion of MSCs. Primary MSCs were subjected to either a control or to a twice-daily LIV regimen for up to sixty cell passages (P60) under in vitro cell expansion conditions. LIV effects were assessed at both early passage (EP) and late passage (LP). At the end of the experiment, P60 cultures exposed to LIV maintained a 28% increase of cell doubling and a 39% reduction in senescence-associated β-galactosidase activity (p < 0.01) but no changes in telomere lengths and p16
Identifiants
pubmed: 32523117
doi: 10.1038/s41598-020-66055-0
pii: 10.1038/s41598-020-66055-0
pmc: PMC7286897
doi:
Substances chimiques
beta-Galactosidase
EC 3.2.1.23
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
9369Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM109095
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059923
Pays : United States
Références
Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science (New York, N.Y.) 284, 143–147, https://doi.org/10.1126/science.284.5411.143 (1999).
doi: 10.1126/science.284.5411.143
Krishnan, V., Bryant, H. U. & MacDougald, O. A. Regulation of bone mass by Wnt signaling. J.Clin.Invest 116, 1202–1209 (2006).
doi: 10.1172/JCI28551
Menuki, K. et al. Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells. Bone 43, 613–620 (2008).
doi: 10.1016/j.bone.2008.04.022
David, V. et al. Mechanical loading down-regulates peroxisome proliferator-activated receptor gamma in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis. Endocrinology 148, 2553–2562 (2007).
doi: 10.1210/en.2006-1704
Einhorn, T. A. & Gerstenfeld, L. C. Fracture healing: mechanisms and interventions. Nature reviews. Rheumatology 11, 45–54, https://doi.org/10.1038/nrrheum.2014.164 (2015).
doi: 10.1038/nrrheum.2014.164
pubmed: 25266456
Pagnotti, G. M. et al. Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity. Nature Reviews Endocrinology, https://doi.org/10.1038/s41574-019-0170-1 (2019).
Puts, R., Albers, J., Kadow-Romacker, A., Geissler, S. & Raum, K. Influence of Donor Age and Stimulation Intensity on Osteogenic Differentiation of Rat Mesenchymal Stromal Cells in Response to Focused Low-Intensity Pulsed Ultrasound. Ultrasound in medicine & biology 42, 2965–2974, https://doi.org/10.1016/j.ultrasmedbio.2016.08.012 (2016).
doi: 10.1016/j.ultrasmedbio.2016.08.012
Maredziak, M., Marycz, K., Tomaszewski, K. A., Kornicka, K. & Henry, B. M. The Influence of Aging on the Regenerative Potential of Human Adipose Derived Mesenchymal Stem Cells. Stem cells international 2016, 2152435, https://doi.org/10.1155/2016/2152435 (2016).
doi: 10.1155/2016/2152435
pubmed: 26941800
pmcid: 4749808
Bernabei, R., Martone, A. M., Ortolani, E., Landi, F. & Marzetti, E. Screening, diagnosis and treatment of osteoporosis: a brief review. Clin Cases Miner Bone Metab 11, 201–207 (2014).
pubmed: 25568654
pmcid: 4269144
Choudhery, M. S., Badowski, M., Muise, A., Pierce, J. & Harris, D. T. Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. Journal of translational medicine 12, 8, https://doi.org/10.1186/1479-5876-12-8 (2014).
doi: 10.1186/1479-5876-12-8
pubmed: 24397850
pmcid: 3895760
Vuori, I. Exercise and physical health: musculoskeletal health and functional capabilities. Research quarterly for exercise and sport 66, 276–285, https://doi.org/10.1080/02701367.1995.10607912 (1995).
doi: 10.1080/02701367.1995.10607912
pubmed: 8775582
Hell, R. C. R. et al. Physical activity improves age-related decline in the osteogenic potential of rats’ bone marrow-derived mesenchymal stem cells. Acta Physiologica 205, 292–301, https://doi.org/10.1111/j.1748-1716.2011.02397.x (2012).
doi: 10.1111/j.1748-1716.2011.02397.x
pubmed: 22168399
Singulani, M. P. et al. Effects of strength training on osteogenic differentiation and bone strength in aging female Wistar rats. Scientific reports 7, 42878, https://doi.org/10.1038/srep42878 (2017).
doi: 10.1038/srep42878
pubmed: 28211481
pmcid: 5314400
Speakman, J. R. & Selman, C. Physical activity and resting metabolic rate. The Proceedings of the Nutrition Society 62, 621–634, https://doi.org/10.1079/pns2003282 (2003).
doi: 10.1079/pns2003282
pubmed: 14692598
Jackson, A. S., Sui, X., Hébert, J. R., Church, T. S. & Blair, S. N. Role of lifestyle and aging on the longitudinal change in cardiorespiratory fitness. Arch Intern Med 169, 1781–1787, https://doi.org/10.1001/archinternmed.2009.312 (2009).
doi: 10.1001/archinternmed.2009.312
pubmed: 19858436
pmcid: 3379873
Wakeling, J. M. & Nigg, B. M. Modification of soft tissue vibrations in the leg by muscular activity. Journal of applied physiology (Bethesda, Md.: 1985) 90, 412–420, https://doi.org/10.1152/jappl.2001.90.2.412 (2001).
doi: 10.1152/jappl.2001.90.2.412
Huang, R. P., Rubin, C. T. & McLeod, K. J. Changes in postural muscle dynamics as a function of age. J Gerontol A Biol Sci Med Sci 54, B352–357 (1999).
doi: 10.1093/gerona/54.8.B352
Marin-Cascales, E. et al. Whole-body vibration training and bone health in postmenopausal women: A systematic review and meta-analysis. Medicine 97, e11918, https://doi.org/10.1097/md.0000000000011918 (2018).
doi: 10.1097/md.0000000000011918
pubmed: 30142802
pmcid: 6112924
Gilsanz, V. et al. Low-Level, High-Frequency Mechanical Signals Enhance Musculoskeletal Development of Young Women With Low BMD. J.Bone Miner.Res. 21, 1464–1474 (2006).
doi: 10.1359/jbmr.060612
Rubin, C., Turner, A. S., Bain, S., Mallinckrodt, C. & McLeod, K. Anabolism. Low mechanical signals strengthen long bones. Nature 412, 603–604, https://doi.org/10.1038/35088122 (2001).
doi: 10.1038/35088122
pubmed: 11493908
Rubin, C. et al. Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res 17, 349–357, https://doi.org/10.1359/jbmr.2002.17.2.349 (2002).
doi: 10.1359/jbmr.2002.17.2.349
pubmed: 11811566
Rubin, C., Xu, G. & Judex, S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 15, 2225–2229, https://doi.org/10.1096/fj.01-0166com (2001).
doi: 10.1096/fj.01-0166com
Uzer, G. et al. Cell Mechanosensitivity to Extremely Low-Magnitude Signals Is Enabled by a LINCed Nucleus. STEM CELLS 33, 2063–2076, https://doi.org/10.1002/stem.2004 (2015).
doi: 10.1002/stem.2004
pubmed: 25787126
pmcid: 4458857
Uzer, G., Pongkitwitoon, S., Ete Chan, M. & Judex, S. Vibration induced osteogenic commitment of mesenchymal stem cells is enhanced by cytoskeletal remodeling but not fluid shear. Journal of biomechanics 46, 2296–2302, https://doi.org/10.1016/j.jbiomech.2013.06.008 (2013).
doi: 10.1016/j.jbiomech.2013.06.008
pubmed: 23870506
pmcid: 3777744
Pongkitwitoon, S., Uzer, G., Rubin, J. & Judex, S. Cytoskeletal Configuration Modulates Mechanically Induced Changes in Mesenchymal Stem Cell Osteogenesis, Morphology, and Stiffness. Scientific reports 6, 34791, https://doi.org/10.1038/srep34791 (2016).
doi: 10.1038/srep34791
pubmed: 27708389
pmcid: 5052530
Uzer, G. et al. Sun-mediated mechanical LINC between nucleus and cytoskeleton regulates betacatenin nuclear access. Journal of biomechanics 74, 32–40, https://doi.org/10.1016/j.jbiomech.2018.04.013 (2018).
doi: 10.1016/j.jbiomech.2018.04.013
pubmed: 29691054
pmcid: 5962429
Touchstone, H. et al. Recovery of stem cell proliferation by low intensity vibration under simulated microgravity requires intact LINC complex npj. Microgravity 5, https://doi.org/10.1038/s41526-019-0072-5 (2019).
Childs, B. G., Durik, M., Baker, D. J. & van Deursen, J. M. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nature medicine 21, 1424–1435, https://doi.org/10.1038/nm.4000 (2015).
doi: 10.1038/nm.4000
pubmed: 26646499
pmcid: 4748967
Phipps, S. M. O., Berletch, J. B., Andrews, L. G. & Tollefsbol, T. O. Aging Cell Culture: Methods and Observations. Methods in molecular biology (Clifton, N.J.) 371, 9–19 (2007).
doi: 10.1007/978-1-59745-361-5_2
Wagner, W. et al. Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells. PLOS ONE 4, e5846, https://doi.org/10.1371/journal.pone.0005846 (2009).
doi: 10.1371/journal.pone.0005846
pubmed: 19513108
pmcid: 2688074
Geissler, S. et al. Functional comparison of chronological and in vitro aging: differential role of the cytoskeleton and mitochondria in mesenchymal stromal cells. PLoS One 7, e52700, https://doi.org/10.1371/journal.pone.0052700 (2012).
doi: 10.1371/journal.pone.0052700
pubmed: 23285157
pmcid: 3532360
Geißler, S. et al. Functional Comparison of Chronological and In Vitro Aging: Differential Role of the Cytoskeleton and Mitochondria in Mesenchymal Stromal Cells. PLOS ONE 7, e52700, https://doi.org/10.1371/journal.pone.0052700 (2012).
doi: 10.1371/journal.pone.0052700
pubmed: 23285157
pmcid: 3532360
Campisi, J. & d’Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8, 729–740, https://doi.org/10.1038/nrm2233 (2007).
doi: 10.1038/nrm2233
pubmed: 17667954
pmcid: 17667954
Sen, B. et al. β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research, https://doi.org/10.1002/jbmr.3975 (2020).
Sen, B. et al. Intranuclear Actin Structure Modulates Mesenchymal Stem Cell Differentiation. Stem Cells 35, 1624–1635, https://doi.org/10.1002/stem.2617 (2017).
doi: 10.1002/stem.2617
pubmed: 28371128
pmcid: 5534840
Sen, B. et al. Intranuclear Actin Regulates Osteogenesis. Stem Cells https://doi.org/10.1002/stem.2090 (2015).
doi: 10.1002/stem.2090
pubmed: 26140478
pmcid: 4788101
Thompson, W. R. et al. Osteocyte specific responses to soluble and mechanical stimuli in a stem cell derived culture model. Scientific reports 5, 11049, https://doi.org/10.1038/srep11049, http://www.nature.com/articles/srep11049#supplementary-information (2015).
Sen, B. et al. mTORC2 Regulates Mechanically Induced Cytoskeletal Reorganization and Lineage Selection in Marrow-Derived Mesenchymal Stem Cells. Journal of Bone and Mineral Research 29, 78–89, https://doi.org/10.1002/jbmr.2031 (2014).
doi: 10.1002/jbmr.2031
pubmed: 23821483
Thompson, W. R. et al. Mechanically Activated Fyn Utilizes mTORC2 to Regulate RhoA and Adipogenesis in Mesenchymal Stem Cells. Stem Cells 31, 2528–2537, https://doi.org/10.1002/stem.1476 (2013).
doi: 10.1002/stem.1476
pubmed: 23836527
pmcid: 4040149
Elsafadi, M. et al. Transgelin is a TGFbeta-inducible gene that regulates osteoblastic and adipogenic differentiation of human skeletal stem cells through actin cytoskeleston organization. Cell death & disease 7, e2321, https://doi.org/10.1038/cddis.2016.196 (2016).
doi: 10.1038/cddis.2016.196
Hamadi, A. et al. Regulation of focal adhesion dynamics and disassembly by phosphorylation of FAK at tyrosine 397. Journal of cell science 118, 4415–4425, https://doi.org/10.1242/jcs.02565 (2005).
doi: 10.1242/jcs.02565
pubmed: 16159962
Jiang, P., Du, W., Mancuso, A., Wellen, K. E. & Yang, X. Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493, 689–693, https://doi.org/10.1038/nature11776 (2013).
doi: 10.1038/nature11776
pubmed: 23334421
pmcid: 3561500
Ho, H.-y et al. Enhanced oxidative stress and accelerated cellular senescence in glucose-6-phosphate dehydrogenase (G6PD)-deficient human fibroblasts. Free Radical Biology and Medicine 29, 156–169, https://doi.org/10.1016/S0891-5849(00)00331-2 (2000).
doi: 10.1016/S0891-5849(00)00331-2
pubmed: 10980404
Wu, Z., Jiang, Q., Clarke, P. R. & Zhang, C. Phosphorylation of Crm1 by CDK1–cyclin-B promotes Ran-dependent mitotic spindle assembly. Journal of cell science 126, 3417–3428, https://doi.org/10.1242/jcs.126854 (2013).
doi: 10.1242/jcs.126854
pubmed: 23729730
Lindqvist, A. & Cyclin, B. –C. 1 activates its own pump to get into the nucleus. The Journal of Cell Biology 189, 197–199, https://doi.org/10.1083/jcb.201003032 (2010).
doi: 10.1083/jcb.201003032
pubmed: 20404105
pmcid: 2856906
Wagner, W. et al. How to track cellular aging of mesenchymal stromal cells? Aging 2, 224–230, https://doi.org/10.18632/aging.100136 (2010).
doi: 10.18632/aging.100136
pubmed: 20453259
pmcid: 2881510
Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460, https://doi.org/10.1038/345458a0 (1990).
doi: 10.1038/345458a0
pubmed: 2342578
Oja, S., Komulainen, P., Penttilä, A., Nystedt, J. & Korhonen, M. Automated image analysis detects aging in clinical-grade mesenchymal stromal cell cultures. Stem cell research & therapy 9, 6–6, https://doi.org/10.1186/s13287-017-0740-x (2018).
doi: 10.1186/s13287-017-0740-x
Legzdina, D., Romanauska, A., Nikulshin, S., Kozlovska, T. & Berzins, U. Characterization of Senescence of Culture-expanded Human Adipose-derived Mesenchymal Stem Cells. Int J Stem Cells 9, 124–136, https://doi.org/10.15283/ijsc.2016.9.1.124 (2016).
doi: 10.15283/ijsc.2016.9.1.124
pubmed: 27426094
pmcid: 4961112
Calado, R. T. & Dumitriu, B. Telomere dynamics in mice and humans. Semin Hematol 50, 165–174, https://doi.org/10.1053/j.seminhematol.2013.03.030 (2013).
doi: 10.1053/j.seminhematol.2013.03.030
pubmed: 23956466
pmcid: 3742037
Baskan, O., Mese, G. & Ozcivici, E. Low-intensity vibrations normalize adipogenesis-induced morphological and molecular changes of adult mesenchymal stem cells. Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine, 954411916687338, https://doi.org/10.1177/0954411916687338 (2017).
Brenner, R. E. et al. Osteogenesis imperfecta: insufficient collagen synthesis in early childhood as evidenced by analysis of compact bone and fibroblast cultures. European journal of clinical investigation 19, 159–166, https://doi.org/10.1111/j.1365-2362.1989.tb00211.x (1989).
doi: 10.1111/j.1365-2362.1989.tb00211.x
pubmed: 2499474
Meyer, M. B., Benkusky, N. A., Sen, B., Rubin, J. & Pike, J. W. Epigenetic Plasticity Drives Adipogenic and Osteogenic Differentiation of Marrow-derived Mesenchymal Stem Cells. Journal of Biological Chemistry 291, 17829–17847, https://doi.org/10.1074/jbc.M116.736538 (2016).
doi: 10.1074/jbc.M116.736538
pubmed: 27402842
Qiang, L., Wang, H. & Farmer, S. R. Adiponectin Secretion Is Regulated by SIRT1 and the Endoplasmic Reticulum Oxidoreductase Ero1-Lα. Molecular and Cellular Biology 27, 4698–4707, https://doi.org/10.1128/mcb.02279-06 (2007).
doi: 10.1128/mcb.02279-06
pubmed: 17452443
pmcid: 1951471
Sikora, E., Mosieniak, G. & Sliwinska, M. A. Morphological and Functional Characteristic of Senescent Cancer Cells. Current drug targets 17, 377–387, https://doi.org/10.2174/1389450116666151019094724 (2016).
doi: 10.2174/1389450116666151019094724
pubmed: 26477465
Chen, Q. M. et al. Involvement of Rb family proteins, focal adhesion proteins and protein synthesis in senescent morphogenesis induced by hydrogen peroxide. Journal of cell science 113(Pt 22), 4087–4097 (2000).
pubmed: 11058095
Balcioglu, H. E., van Hoorn, H., Donato, D. M., Schmidt, T. & Danen, E. H. J. The integrin expression profile modulates orientation and dynamics of force transmission at cell–matrix adhesions. Journal of cell science 128, 1316–1326, https://doi.org/10.1242/jcs.156950 (2015).
doi: 10.1242/jcs.156950
pubmed: 25663698
Blanchoin, L., Boujemaa-Paterski, R., Sykes, C. & Plastino, J. Actin Dynamics, Architecture, and Mechanics in Cell Motility. Physiological Reviews 94, 235–263, https://doi.org/10.1152/physrev.00018.2013 (2014).
doi: 10.1152/physrev.00018.2013
pubmed: 24382887
Burridge, K. & Wittchen, E. S. The tension mounts: Stress fibers as force-generating mechanotransducers. The Journal of Cell Biology 200, 9–19, https://doi.org/10.1083/jcb.201210090 (2013).
doi: 10.1083/jcb.201210090
pubmed: 23295347
pmcid: 3542796
Peister, A. et al. Adult stem cells from bone marrow (MSCs) isolated from different strains of inbred mice vary in surface epitopes, rates of proliferation, and differentiation potential. Vol. 103 (2004).
Case, N. et al. Mechanical activation of β-catenin regulates phenotype in adult murine marrow-derived mesenchymal stem cells. Journal of Orthopaedic Research 28, 1531–1538, https://doi.org/10.1002/jor.21156 (2010).
doi: 10.1002/jor.21156
pubmed: 20872592
pmcid: 3046385
Roos, G. et al. Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood 111, 2246–2252, https://doi.org/10.1182/blood-2007-05-092759 (2008).
doi: 10.1182/blood-2007-05-092759
pubmed: 18045969
Hudon, S. F. et al. Universal assay for measuring vertebrate telomeres by real-time quantitative PCR. bioRxiv, 797068, https://doi.org/10.1101/797068 (2019).
Uzer, G. et al. Gap Junctional Communication in Osteocytes Is Amplified by Low Intensity Vibrations In Vitro. PLoS ONE 9, e90840, https://doi.org/10.1371/journal.pone.0090840 (2014).
doi: 10.1371/journal.pone.0090840
pubmed: 24614887
pmcid: 3948700
Pu, X. & Oxford, J. T. Proteomic Analysis of Engineered Cartilage. Methods Mol Biol 1340, 263–278, https://doi.org/10.1007/978-1-4939-2938-2_19 (2015).
doi: 10.1007/978-1-4939-2938-2_19
pubmed: 26445845
pmcid: 4762595