References

1. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA A Cancer J. Clin. 2020, 70, 7–30.
2. López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The hallmarks of aging. Cell 2013, 153, 1194–1217.
3. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674.
4. Rodriguez-Abreu, D.; Bordoni, A.; Zucca, E. Epidemiology of hematological malignancies. Ann. Oncol. Off. J. Eur. Soc. Med Oncol. 2007, 18 (Suppl. 1), i3–i8.
5. Morrison, S.J.; Scadden, D.T. The bone marrow niche for haematopoietic stem cells. Nature 2014, 505, 327–334.
6. Taichman, R.S.; Emerson, S.G. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J. Exp. Med. 1994, 179, 1677–1682.
7. Zhang, J.; Niu, C.; Ye, L.; Huang, H.; He, X.; Tong, W.G.; Ross, J.; Haug, J.; Johnson, T.; Feng, J.Q.; et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003, 425, 836–841.
8. Geiger, H.; Denkinger, M.; Schirmbeck, R. Hematopoietic stem cell aging. Curr. Opin. Immunol. 2014, 29, 86–92.
9. Hellmich, C.; Moore, J.A.; Bowles, K.M.; Rushworth, S.A. Bone Marrow Senescence and the Microenvironment of Hematological Malignancies. Front. Oncol. 2020, 10, 230.
10. Dominici, M.; Le Blanc, K.; Mueller, I.; Slaper-Cortenbach, I.; Marini, F.; Krause, D.; Deans, R.; Keating, A.; Prockop, D.; Horwitz, E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006, 8, 315–317.
11. Direkze, N.C.; Hodivala-Dilke, K.; Jeffery, R.; Hunt, T.; Poulsom, R.; Oukrif, D.; Alison, M.R.; Wright, N.A. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004, 64, 8492–8495.
12. Pittenger, M.F.; Mackay, A.M.; Beck, S.C.; Jaiswal, R.K.; Douglas, R.; Mosca, J.D.; Moorman, M.A.; Simonetti, D.W.; Craig, S.; Marshak, D.R. Multilineage potential of adult human mesenchymal stem cells. Science (N. Y.) 1999, 284, 143–147.
13. Glenn, J.D.; Whartenby, K.A. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy. World J. Stem Cells 2014, 6, 526–539.
14. Majumdar, M.K.; Thiede, M.A.; Haynesworth, S.E.; Bruder, S.P.; Gerson, S.L. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J. Hematotherapy Stem Cell Res. 2000, 9, 841–848.
15. Xie, H.; Sun, L.; Zhang, L.; Liu, T.; Chen, L.; Zhao, A.; Lei, Q.; Gao, F.; Zou, P.; Li, Q.; et al. Mesenchymal Stem Cell-Derived Microvesicles Support Ex Vivo Expansion of Cord Blood-Derived CD34(+) Cells. Stem Cells Int. 2016, 2016, 6493241.
16. Mardpour, S.; Hamidieh, A.A.; Taleahmad, S.; Sharifzad, F.; Taghikhani, A.; Baharvand, H. Interaction between mesenchymal stromal cell-derived extracellular vesicles and immune cells by distinct protein content. J. Cell. Physiol. 2019, 234, 8249–8258.
17. Toh, W.S.; Zhang, B.; Lai, R.C.; Lim, S.K. Immune regulatory targets of mesenchymal stromal cell exosomes/small extracellular vesicles in tissue regeneration. Cytotherapy 2018, 20, 1419–1426.
18. Fafián-Labora, J.A.; Morente-López, M.; Arufe, M.C. Effect of aging on behaviour of mesenchymal stem cells. World J. Stem Cells 2019, 11, 337–346.
19. Lei, Q.; Liu, T.; Gao, F.; Xie, H.; Sun, L.; Zhao, A.; Ren, W.; Guo, H.; Zhang, L.; Wang, H.; et al. Microvesicles as Potential Biomarkers for the Identification of Senescence in Human Mesenchymal Stem Cells. Theranostics 2017, 7, 2673–2689.
20. Bron, D.; Ades, L.; Fulop, T.; Goede, V. Aging and malignant hemopathies. Haematologica 2015, 100, 571–574.
21. Ergen, A.V.; Boles, N.C.; Goodell, M.A. Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing. Blood 2012, 119, 2500–2509.
22. Berliner, N. Anemia in the elderly. Trans. Am. Clin. Climatol. Assoc. 2013, 124, 230–237.
23. Mejia-Ramirez, E.; Florian, M.C. Understanding intrinsic hematopoietic stem cell aging. Haematologica 2020, 105, 22–37.
24. Hayflick, L. THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Exp. Cell Res. 1965, 37, 614–636.
25. Choo, K.B.; Tai, L.; Hymavathee, K.S.; Wong, C.Y.; Nguyen, P.N.; Huang, C.J.; Cheong, S.K.; Kamarul, T. Oxidative stress-induced premature senescence in Wharton’s jelly-derived mesenchymal stem cells. Int. J. Med Sci. 2014, 11, 1201–1207.
26. Baxter, M.A.; Wynn, R.F.; Jowitt, S.N.; Wraith, J.E.; Fairbairn, L.J.; Bellantuono, I. Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells (Dayt. Ohio) 2004, 22, 675–682.
27. Cmielova, J.; Havelek, R.; Soukup, T.; Jiroutová, A.; Visek, B.; Suchánek, J.; Vavrova, J.; Mokry, J.; Muthna, D.; Bruckova, L.; et al. Gamma radiation induces senescence in human adult mesenchymal stem cells from bone marrow and periodontal ligaments. Int. J. Radiat. Biol. 2012, 88, 393–404.
28. Idda, M.L.; McClusky, W.G.; Lodde, V.; Munk, R.; Abdelmohsen, K.; Rossi, M.; Gorospe, M. Survey of senescent cell markers with age in human tissues. Aging 2020, 12, 4052–4066.
29. Zhou, S.; Greenberger, J.S.; Epperly, M.W.; Goff, J.P.; Adler, C.; Leboff, M.S.; Glowacki, J. Age-related intrinsic changes in human bone-marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell 2008, 7, 335–343.
30. Gharibi, B.; Farzadi, S.; Ghuman, M.; Hughes, F.J. Inhibition of Akt/mTOR attenuates age-related changes in mesenchymal stem cells. Stem Cells (Dayt. Ohio) 2014, 32, 2256–2266.
31. Ji, J.; Wu, Y.; Meng, Y.; Zhang, L.; Feng, G.; Xia, Y.; Xue, W.; Zhao, S.; Gu, Z.; Shao, X. JAK-STAT signaling mediates the senescence of bone marrow-mesenchymal stem cells from systemic lupus erythematosus patients. Acta Biochim. Biophys. Sin. 2017, 49, 208–215.
32. Griukova, A.; Deryabin, P.; Sirotkina, M.; Shatrova, A.; Nikolsky, N.; Borodkina, A. P38 MAPK inhibition prevents polybrene-induced senescence of human mesenchymal stem cells during viral transduction. PLoS ONE 2018, 13, e0209606.
33. Li, X.; Hong, Y.; He, H.; Jiang, G.; You, W.; Liang, X.; Fu, Q.; Han, S.; Lian, Q.; Zhang, Y. FGF21 Mediates Mesenchymal Stem Cell Senescence via Regulation of Mitochondrial Dynamics. Oxidative Med. Cell. Longev. 2019, 2019, 4915149.
34. Neri, S.; Borzì, R.M. Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging. Biomolecules 2020, 10, 340.
35. Cakouros, D.; Gronthos, S. Epigenetic Regulation of Bone Marrow Stem Cell Aging: Revealing Epigenetic Signatures associated with Hematopoietic and Mesenchymal Stem Cell Aging. Aging Dis. 2019, 10, 174–189.
36. Bork, S.; Pfister, S.; Witt, H.; Horn, P.; Korn, B.; Ho, A.D.; Wagner, W. DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells. Aging Cell 2010, 9, 54–63.
37. Fernández, A.F.; Bayón, G.F.; Urdinguio, R.G.; Toraño, E.G.; García, M.G.; Carella, A.; Petrus-Reurer, S.; Ferrero, C.; Martinez-Camblor, P.; Cubillo, I.; et al. H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells. Genome Res. 2015, 25, 27–40.
38. Yuan, H.F.; Zhai, C.; Yan, X.L.; Zhao, D.D.; Wang, J.X.; Zeng, Q.; Chen, L.; Nan, X.; He, L.J.; Li, S.T.; et al. SIRT1 is required for long-term growth of human mesenchymal stem cells. J. Mol. Med. (Berl. Ger.) 2012, 90, 389–400.
39. Simic, P.; Zainabadi, K.; Bell, E.; Sykes, D.B.; Saez, B.; Lotinun, S.; Baron, R.; Scadden, D.; Schipani, E.; Guarente, L. SIRT1 regulates differentiation of mesenchymal stem cells by deacetylating β-catenin. EMBO Mol. Med. 2013, 5, 430–440.
40. Peffers, M.J.; Collins, J.; Fang, Y.; Goljanek-Whysall, K.; Rushton, M.; Loughlin, J.; Proctor, C.; Clegg, P.D. Age-related changes in mesenchymal stem cells identified using a multi-omics approach. Eur. Cells Mater. 2016, 31, 136–159.
41. Pan, H.; Guan, D.; Liu, X.; Li, J.; Wang, L.; Wu, J.; Zhou, J.; Zhang, W.; Ren, R.; Zhang, W.; et al. SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res. 2016, 26, 190–205.
42. Kurosawa, S.; Iwama, A. Aging and leukemic evolution of hematopoietic stem cells under various stress conditions. Inflamm. Regen. 2020, 40, 29.
43. So, A.Y.; Jung, J.W.; Lee, S.; Kim, H.S.; Kang, K.S. DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs. PLoS ONE 2011, 6, e19503.
44. Yang, R.; Yu, T.; Kou, X.; Gao, X.; Chen, C.; Liu, D.; Zhou, Y.; Shi, S. Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter. Nat. Commun. 2018, 9, 2143.
45. Li, R.; Zhou, Y.; Cao, Z.; Liu, L.; Wang, J.; Chen, Z.; Xing, W.; Chen, S.; Bai, J.; Yuan, W.; et al. TET2 Loss Dysregulates the Behavior of Bone Marrow Mesenchymal Stromal Cells and Accelerates Tet2(−/−)-Driven Myeloid Malignancy Progression. Stem Cell Rep. 2018, 10, 166–179.
46. Zhang, P.; Chen, Z.; Li, R.; Guo, Y.; Shi, H.; Bai, J.; Yang, H.; Sheng, M.; Li, Z.; Li, Z.; et al. Loss of ASXL1 in the bone marrow niche dysregulates hematopoietic stem and progenitor cell fates. Cell Discov. 2018, 4, 4.
47. Malaquin, N.; Martinez, A.; Rodier, F. Keeping the senescence secretome under control: Molecular reins on the senescence-associated secretory phenotype. Exp. Gerontol. 2016, 82, 39–49.
48. Mavrogonatou, E.; Pratsinis, H.; Papadopoulou, A.; Karamanos, N.K.; Kletsas, D. Extracellular matrix alterations in senescent cells and their significance in tissue homeostasis. Matrix Biol. J. Int. Soc. Matrix Biol. 2019, 75–76, 27–42.
49. Lee, B.C.; Yu, K.R. Impact of mesenchymal stem cell senescence on inflammaging. BMB Rep. 2020, 53, 65–73.
50. O’Hagan-Wong, K.; Nadeau, S.; Carrier-Leclerc, A.; Apablaza, F.; Hamdy, R.; Shum-Tim, D.; Rodier, F.; Colmegna, I. Increased IL-6 secretion by aged human mesenchymal stromal cells disrupts hematopoietic stem and progenitor cells’ homeostasis. Oncotarget 2016, 7, 13285–13296.
51. Gnani, D.; Crippa, S.; Della Volpe, L.; Rossella, V.; Conti, A.; Lettera, E.; Rivis, S.; Ometti, M.; Fraschini, G.; Bernardo, M.E.; et al. An early-senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro-inflammatory program. Aging Cell 2019, 18, e12933.
52. Urbanelli, L.; Buratta, S.; Sagini, K.; Tancini, B.; Emiliani, C. Extracellular Vesicles as New Players in Cellular Senescence. Int. J. Mol. Sci. 2016, 17, 1408.
53. Kulkarni, R.; Bajaj, M.; Ghode, S.; Jalnapurkar, S.; Limaye, L.; Kale, V.P. Intercellular Transfer of Microvesicles from Young Mesenchymal Stromal Cells Rejuvenates Aged Murine Hematopoietic Stem Cells. Stem Cells (Dayt. Ohio) 2018, 36, 420–433.
54. Terlecki-Zaniewicz, L.; Lämmermann, I.; Latreille, J.; Bobbili, M.R.; Pils, V.; Schosserer, M.; Weinmüllner, R.; Dellago, H.; Skalicky, S.; Pum, D.; et al. Small extracellular vesicles and their miRNA cargo are anti-apoptotic members of the senescence-associated secretory phenotype. Aging 2018, 10, 1103–1132.
55. Robbins, P.D. Extracellular vesicles and aging. Stem Cell Investig. 2017, 4, 98.
56. Franceschi, C.; Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. Ser. ABiol. Sci. Med Sci. 2014, 69 (Suppl. 1), S4–S9.
57. Rea, I.M.; Gibson, D.S.; McGilligan, V.; McNerlan, S.E.; Alexander, H.D.; Ross, O.A. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front. Immunol. 2018, 9, 586.
58. Najar, M.; Ouhaddi, Y.; Bouhtit, F.; Melki, R.; Afif, H.; Boukhatem, N.; Merimi, M.; Fahmi, H. Empowering the immune fate of bone marrow mesenchymal stromal cells: Gene and protein changes. Inflamm. Res. 2019, 68, 167–176.
59. Romieu-Mourez, R.; François, M.; Boivin, M.N.; Bouchentouf, M.; Spaner, D.E.; Galipeau, J. Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype. J. Immunol. 2009, 182, 7963–7973.
60. Minciullo, P.L.; Catalano, A.; Mandraffino, G.; Casciaro, M.; Crucitti, A.; Maltese, G.; Morabito, N.; Lasco, A.; Gangemi, S.; Basile, G. Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity. Arch. Immunol. Ther. Exp. 2016, 64, 111–126.
61. Fulop, T.; Witkowski, J.M.; Olivieri, F.; Larbi, A. The integration of inflammaging in age-related diseases. Semin. Immunol. 2018, 40, 17–35.
62. Zhao, J.L.; Ma, C.; O’Connell, R.M.; Mehta, A.; DiLoreto, R.; Heath, J.R.; Baltimore, D. Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell 2014, 14, 445–459.
63. Ratushnyy, A.; Ezdakova, M.; Buravkova, L. Secretome of Senescent Adipose-Derived Mesenchymal Stem Cells Negatively Regulates Angiogenesis. Int. J. Mol. Sci. 2020, 21, 1802.
64. Goedhart, M.; Cornelissen, A.S.; Kuijk, C.; Geerman, S.; Kleijer, M.; van Buul, J.D.; Huveneers, S.; Raaijmakers, M.; Young, H.A.; Wolkers, M.C.; et al. Interferon-Gamma Impairs Maintenance and Alters Hematopoietic Support of Bone Marrow Mesenchymal Stromal Cells. Stem Cells Dev. 2018, 27, 579–589.
65. Waterman, R.S.; Tomchuck, S.L.; Henkle, S.L.; Betancourt, A.M. A new mesenchymal stem cell (MSC) paradigm: Polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS ONE 2010, 5, e10088.
66. Ren, G.; Zhang, L.; Zhao, X.; Xu, G.; Zhang, Y.; Roberts, A.I.; Zhao, R.C.; Shi, Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008, 2, 141–150.
67. Kim, J.; Hematti, P. Mesenchymal stem cell-educated macrophages: A novel type of alternatively activated macrophages. Exp. Hematol. 2009, 37, 1445–1453.
68. Sepúlveda, J.C.; Tomé, M.; Fernández, M.E.; Delgado, M.; Campisi, J.; Bernad, A.; González, M.A. Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model. Stem Cells (Dayt. Ohio) 2014, 32, 1865–1877.
69. Yu, K.R.; Lee, J.Y.; Kim, H.S.; Hong, I.S.; Choi, S.W.; Seo, Y.; Kang, I.; Kim, J.J.; Lee, B.C.; Lee, S.; et al. A p38 MAPK-mediated alteration of COX-2/PGE2 regulates immunomodulatory properties in human mesenchymal stem cell aging. PLoS ONE 2014, 9, e102426.
70. Yin, Y.; Wu, R.X.; He, X.T.; Xu, X.Y.; Wang, J.; Chen, F.M. Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture. Stem Cell Res. Ther. 2017, 8, 153.
71. Huang, R.; Qin, C.; Wang, J.; Hu, Y.; Zheng, G.; Qiu, G.; Ge, M.; Tao, H.; Shu, Q.; Xu, J. Differential effects of extracellular vesicles from aging and young mesenchymal stem cells in acute lung injury. Aging 2019, 11, 7996–8014.
72. Ziegler, P.; Boettcher, S.; Takizawa, H.; Manz, M.G.; Brümmendorf, T.H. LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance. Ann. Hematol. 2016, 95, 173–178.
73. Shi, C.; Jia, T.; Mendez-Ferrer, S.; Hohl, T.M.; Serbina, N.V.; Lipuma, L.; Leiner, I.; Li, M.O.; Frenette, P.S.; Pamer, E.G. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. Immunity 2011, 34, 590–601.
74. Granero-Moltó, F.; Weis, J.A.; Miga, M.I.; Landis, B.; Myers, T.J.; O’Rear, L.; Longobardi, L.; Jansen, E.D.; Mortlock, D.P.; Spagnoli, A. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells (Dayt. Ohio) 2009, 27, 1887–1898.
75. Coipeau, P.; Rosset, P.; Langonne, A.; Gaillard, J.; Delorme, B.; Rico, A.; Domenech, J.; Charbord, P.; Sensebe, L. Impaired differentiation potential of human trabecular bone mesenchymal stromal cells from elderly patients. Cytotherapy 2009, 11, 584–594.
76. Wagner, W.; Horn, P.; Castoldi, M.; Diehlmann, A.; Bork, S.; Saffrich, R.; Benes, V.; Blake, J.; Pfister, S.; Eckstein, V.; et al. Replicative senescence of mesenchymal stem cells: A continuous and organized process. PLoS ONE 2008, 3, e2213.
77. Justesen, J.; Stenderup, K.; Eriksen, E.F.; Kassem, M. Maintenance of osteoblastic and adipocytic differentiation potential with age and osteoporosis in human marrow stromal cell cultures. Calcif. Tissue Int. 2002, 71, 36–44.
78. Fickert, S.; Schröter-Bobsin, U.; Gross, A.F.; Hempel, U.; Wojciechowski, C.; Rentsch, C.; Corbeil, D.; Günther, K.P. Human mesenchymal stem cell proliferation and osteogenic differentiation during long-term ex vivo cultivation is not age dependent. J. Bone Miner. Metab. 2011, 29, 224–235.
79. Stolzing, A.; Jones, E.; McGonagle, D.; Scutt, A. Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies. Mech. Ageing Dev. 2008, 129, 163–173.
80. Zaim, M.; Karaman, S.; Cetin, G.; Isik, S. Donor age and long-term culture affect differentiation and proliferation of human bone marrow mesenchymal stem cells. Ann. Hematol. 2012, 91, 1175–1186.
81. Zhang, W.; Ou, G.; Hamrick, M.; Hill, W.; Borke, J.; Wenger, K.; Chutkan, N.; Yu, J.; Mi, Q.S.; Isales, C.M.; et al. Age-related changes in the osteogenic differentiation potential of mouse bone marrow stromal cells. J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res. 2008, 23, 1118–1128.
82. Alameda, D.; Saez, B.; Lara-Astiaso, D.; Sarvide, S.; Lasa, M.; Alignani, D.; Rodriguez, I.; Garate, S.; Vilas, A.; Paiva, B.; et al. Characterization of freshly isolated mesenchymal stromal cells from healthy and multiple myeloma bone marrow: Transcriptional modulation of the microenvironment. Haematologica 2020, 105.
83. Komori, T. Regulation of osteoblast differentiation by transcription factors. J. Cell. Biochem. 2006, 99, 1233–1239.
84. Nakashima, K.; Zhou, X.; Kunkel, G.; Zhang, Z.; Deng, J.M.; Behringer, R.R.; de Crombrugghe, B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002, 108, 17–29.
85. Lefterova, M.I.; Zhang, Y.; Steger, D.J.; Schupp, M.; Schug, J.; Cristancho, A.; Feng, D.; Zhuo, D.; Stoeckert, C.J., Jr.; Liu, X.S.; et al. PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale. Genes Dev. 2008, 22, 2941–2952.
86. Li, H.; Liu, P.; Xu, S.; Li, Y.; Dekker, J.D.; Li, B.; Fan, Y.; Zhang, Z.; Hong, Y.; Yang, G.; et al. FOXP1 controls mesenchymal stem cell commitment and senescence during skeletal aging. J. Clin. Investig. 2017, 127, 1241–1253.
87. Wu, M.; Wang, Y.; Shao, J.Z.; Wang, J.; Chen, W.; Li, Y.P. Cbfβ governs osteoblast-adipocyte lineage commitment through enhancing β-catenin signaling and suppressing adipogenesis gene expression. Proc. Natl. Acad. Sci. USA 2017, 114, 10119–10124.
88. Nishikawa, K.; Nakashima, T.; Takeda, S.; Isogai, M.; Hamada, M.; Kimura, A.; Kodama, T.; Yamaguchi, A.; Owen, M.J.; Takahashi, S.; et al. Maf promotes osteoblast differentiation in mice by mediating the age-related switch in mesenchymal cell differentiation. J. Clin. Investig. 2010, 120, 3455–3465.
89. Moerman, E.J.; Teng, K.; Lipschitz, D.A.; Lecka-Czernik, B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: The role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways. Aging Cell 2004, 3, 379–389.
90. Davis, C.; Dukes, A.; Drewry, M.; Helwa, I.; Johnson, M.H.; Isales, C.M.; Hill, W.D.; Liu, Y.; Shi, X.; Fulzele, S.; et al. MicroRNA-183-5p Increases with Age in Bone-Derived Extracellular Vesicles, Suppresses Bone Marrow Stromal (Stem) Cell Proliferation, and Induces Stem Cell Senescence. Tissue Eng. Part A 2017, 23, 1231–1240.
91. Xu, R.; Shen, X.; Si, Y.; Fu, Y.; Zhu, W.; Xiao, T.; Fu, Z.; Zhang, P.; Cheng, J.; Jiang, H. MicroRNA-31a-5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment. Aging Cell 2018, 17, e12794.
92. Guidi, N.; Sacma, M.; Ständker, L.; Soller, K.; Marka, G.; Eiwen, K.; Weiss, J.M.; Kirchhoff, F.; Weil, T.; Cancelas, J.A.; et al. Osteopontin attenuates aging-associated phenotypes of hematopoietic stem cells. EMBO J. 2017, 36, 840–853.
93. Stier, S.; Ko, Y.; Forkert, R.; Lutz, C.; Neuhaus, T.; Grünewald, E.; Cheng, T.; Dombkowski, D.; Calvi, L.M.; Rittling, S.R.; et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J. Exp. Med. 2005, 201, 1781–1791.
94. Kennedy, D.E.; Knight, K.L. Inhibition of B Lymphopoiesis by Adipocytes and IL-1-Producing Myeloid-Derived Suppressor Cells. J. Immunol. 2015, 195, 2666–2674.
95. Aguilar-Navarro, A.G.; Meza-León, B.; Gratzinger, D.; Juárez-Aguilar, F.G.; Chang, Q.; Ornatsky, O.; Tsui, H.; Esquivel-Gómez, R.; Hernández-Ramírez, A.; Xie, S.Z.; et al. Human Aging Alters the Spatial Organization between CD34+ Hematopoietic Cells and Adipocytes in Bone Marrow. Stem Cell Rep. 2020, 15, 317–325.
96. Ambrosi, T.H.; Scialdone, A.; Graja, A.; Gohlke, S.; Jank, A.M.; Bocian, C.; Woelk, L.; Fan, H.; Logan, D.W.; Schürmann, A.; et al. Adipocyte Accumulation in the Bone Marrow during Obesity and Aging Impairs Stem Cell-Based Hematopoietic and Bone Regeneration. Cell Stem Cell 2017, 20, 771–784.e776.
97. Mau, T.; Yung, R. Adipose tissue inflammation in aging. Exp. Gerontol. 2018, 105, 27–31.
98. Tormin, A.; Brune, J.C.; Olsson, E.; Valcich, J.; Neuman, U.; Olofsson, T.; Jacobsen, S.E.; Scheding, S. Characterization of bone marrow-derived mesenchymal stromal cells (MSC) based on gene expression profiling of functionally defined MSC subsets. Cytotherapy 2009, 11, 114–128.
99. Kuçi, S.; Kuçi, Z.; Kreyenberg, H.; Deak, E.; Pütsch, K.; Huenecke, S.; Amara, C.; Koller, S.; Rettinger, E.; Grez, M.; et al. CD271 antigen defines a subset of multipotent stromal cells with immunosuppressive and lymphohematopoietic engraftment-promoting properties. Haematologica 2010, 95, 651–659.
100. Flores-Figueroa, E.; Varma, S.; Montgomery, K.; Greenberg, P.L.; Gratzinger, D. Distinctive contact between CD34+ hematopoietic progenitors and CXCL12+ CD271+ mesenchymal stromal cells in benign and myelodysplastic bone marrow. Lab. Investig. 2012, 92, 1330–1341.
101. Li, H.; Ghazanfari, R.; Zacharaki, D.; Ditzel, N.; Isern, J.; Ekblom, M.; Méndez-Ferrer, S.; Kassem, M.; Scheding, S. Low/negative expression of PDGFR-α identifies the candidate primary mesenchymal stromal cells in adult human bone marrow. Stem Cell Rep. 2014, 3, 965–974.
102. Tormin, A.; Li, O.; Brune, J.C.; Walsh, S.; Schütz, B.; Ehinger, M.; Ditzel, N.; Kassem, M.; Scheding, S. CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization. Blood 2011, 117, 5067–5077.
103. Maijenburg, M.W.; Kleijer, M.; Vermeul, K.; Mul, E.P.; van Alphen, F.P.; van der Schoot, C.E.; Voermans, C. The composition of the mesenchymal stromal cell compartment in human bone marrow changes during development and aging. Haematologica 2012, 97, 179–183.
104. Duscher, D.; Rennert, R.C.; Januszyk, M.; Anghel, E.; Maan, Z.N.; Whittam, A.J.; Perez, M.G.; Kosaraju, R.; Hu, M.S.; Walmsley, G.G.; et al. Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells. Sci. Rep. 2014, 4, 7144.
105. Khong, S.M.L.; Lee, M.; Kosaric, N.; Khong, D.M.; Dong, Y.; Hopfner, U.; Aitzetmüller, M.M.; Duscher, D.; Schäfer, R.; Gurtner, G.C. Single-Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age-Related Cellular Subpopulation Depletion and Impaired Regenerative Function. Stem Cells (Dayt. Ohio) 2019, 37, 240–246.
106. Isern, J.; García-García, A.; Martín, A.M.; Arranz, L.; Martín-Pérez, D.; Torroja, C.; Sánchez-Cabo, F.; Méndez-Ferrer, S. The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function. eLife 2014, 3, e03696.
107. Wang, X.; Zou, X.; Zhao, J.; Wu, X.; Lingling, E.; Feng, L.; Wang, D.; Zhang, G.; Xing, H.; Liu, H. Site-Specific Characteristics of Bone Marrow Mesenchymal Stromal Cells Modify the Effect of Aging on the Skeleton. Rejuvenation Res. 2016, 19, 351–361.