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194. Hu C, Li L. Preconditioning Influences Mesenchymal Stem Cell Properties In Vitro and In Vivo. *J Cell Mol Med* (2018) 22:1428-42. doi: 10.1111/jcmm.13492

195. Jiang W, Xu J. Immune Modulation by Mesenchymal Stem Cells. *Cell Prolif* (2020) 53:e12712. doi: 10.1111/cpr.12712

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197. Shi Y, Wang Y, Li Q, Liu K, Hou J, Shao C, et al. Immunoregulatory Mechanisms of Mesenchymal Stem and Stromal Cells in Inflammatory Diseases. *Nat Rev Nephrol* (2018) 14:493-507. doi: 10.1038/s41581-018-0023-5

198. Oh J, Lee YD, Wagers AJ. Stem Cell Aging: Mechanisms, Regulators and Therapeutic Opportunities. *Nat Med* (2014) 20:870-80. doi: 10.1038/nm.3651

199. Sethe S, Scutt A, Stolzing A. Aging of Mesenchymal Stem Cells. *Ageing Res Rev* (2006) 5:91-116. doi: 10.1016/j.arr.2005.10.001

200. Fafian-Labora JA, Morente-Lopez M, Arufe MC. Effect of Aging on Behaviour of Mesenchymal Stem Cells. *World J Stem Cells* (2019) 11:337-46. doi: 10.4252/wjsc.v11.i6.337

201. Li Y, Wu Q, Wang Y, Li L, Bu H, Bao J. Senescence of Mesenchymal Stem Cells (Review). *Int J Mol Med* (2017) 39:775-82. doi: 10.3892/ijmm.2017.2912

202. Turinetto V, Vitale E, Giachino C. Senescence in Human Mesenchymal Stem Cells: Functional Changes and Implications in Stem Cell-Based Therapy. *Int J Mol Sci* (2016) 17(7):1164. doi: 10.3390/ijms17071164

203. Lepperdinger G. Inflammation and Mesenchymal Stem Cell Aging. *Curr Opin Immunol* (2011) 23:518-24. doi: 10.1016/j.coi.2011.05.007

204. Lunyak VV, Amaro-Ortiz A, Gaur M. Mesenchymal Stem Cells Secretory Responses: Senescence Messaging Secretome and Immunomodulation Perspective. *Front Genet* (2017) 8:220. doi: 10.3389/fgene.2017.00220

205. Malaise O, Tachikart Y, Constantinides M, Mumme M, Ferreira-Lopez R, Noack S, et al. Mesenchymal Stem Cell Senescence Alleviates Their Intrinsic and Seno-Suppressive Paracrine Properties Contributing to Osteoarthritis Development. *Aging (Albany NY)* (2019) 11:9128-46. doi: 10.18632/aging.102379

206. Vono R, Jover Garcia E, Spinetti G, Madeddu P. Oxidative Stress in Mesenchymal Stem Cell Senescence: Regulation by Coding and Noncoding Rnas. *Antioxid Redox Signal* (2018) 29:864-79. doi: 10.1089/ars.2017.7294

207. Ho YH, Del Toro R, Rivera-Torres J, Rak J, Korn C, Garcia-Garcia A, et al. Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion During Premature or Physiological Aging. *Cell Stem Cell* (2019) 25:407-418 e406. doi: 10.1016/j.stem.2019.06.007

208. Collins JA, Diekman BO, Loeser RF. Targeting Aging for Disease Modification in Osteoarthritis. *Curr Opin Rheumatol* (2018) 30:101-7. doi: 10.1097/BOR.0000000000000456

209. Greene MA, Loeser RF. Aging-related Inflammation in Osteoarthritis. *Osteoarthritis Cartilage* (2015) 23:1966-71. doi: 10.1016/j.joca.2015.01.008

210. Ebersole JL, Graves CL, Gonzalez OA, Dawson D,3, Morford LA, Huja PE, et al. Aging, Inflammation, Immunity and Periodontal Disease. *Periodontol 2000* (2016) 72:54-75. doi: 10.1111/prd.12135

211. Halim M, Halim A. The Effects of Inflammation, Aging and Oxidative Stress on the Pathogenesis of Diabetes Mellitus (Type 2 Diabetes). *Diabetes Metab Syndr* (2019) 13:1165-72. doi: 10.1016/j.dsx.2019.01.040

212. Lo Furno D, Mannino G, Giuffrida R. Functional Role of Mesenchymal Stem Cells in the Treatment of Chronic Neurodegenerative Diseases. *J Cell Physiol* (2018) 233:3982-99. doi: 10.1002/jcp.26192

213. Staff NP, Jones DT, Singer W. Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases. *Mayo Clin Proc* (2019) 94:892-905. doi: 10.1016/j.mayocp.2019.01.001

214. Oliva AA, McClain-Moss L, Pena A, Drouillard A, Hare JM. Allogeneic Mesenchymal Stem Cell Therapy: A Regenerative Medicine Approach to Geroscience. *Aging Med (Milton)* (2019) 2:142-6. doi: 10.1002/agm2.12079

215. Han X, Wang R, Zhou Y, Fei L, Sun H, Lai S, et al. Mapping the Mouse Cell Atlas by Microwell-Seq. *Cell* (2018) 172:1091-1107 e1017. doi: 10.1016/j.cell.2018.02.001

216. Chen G, Yung R. Meta-Inflammating At the Crossroad of Geroscience. *Aging Med (Milton)* (2019) 2:157-61. doi: 10.1002/agm2.12078

**Conflict of Interest:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Planat-Benard, Varin and Casteilla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Therapeutic Potential by Cellular Pre-Conditioning. *Front Immunol* (2018) 9:2837. doi: 10.3389/fimmu.2018.02837

194. Hu C, Li L. Preconditioning Influences Mesenchymal Stem Cell Properties In Vitro and In Vivo. *J Cell Mol Med* (2018) 22:1428-42. doi: 10.1111/jcmm.13492

195. Jiang W, Xu J. Immune Modulation by Mesenchymal Stem Cells. *Cell Prolif* (2020) 53:e12712. doi: 10.1111/cpr.12712

196. Krampera M. Mesenchymal Stromal Cell 'Licensing': A Multistep Process. *Leukemia* (2011) 25:1408-14. doi: 10.1038/leu.2011.108

197. Shi Y, Wang Y, Li Q, Liu K, Hou J, Shao C, et al. Immunoregulatory Mechanisms of Mesenchymal Stem and Stromal Cells in Inflammatory Diseases. *Nat Rev Nephrol* (2018) 14:493-507. doi: 10.1038/s41581-018-0023-5

198. Oh J, Lee YD, Wagers AJ. Stem Cell Aging: Mechanisms, Regulators and Therapeutic Opportunities. *Nat Med* (2014) 20:870-80. doi: 10.1038/nm.3651

199. Sethe S, Scutt A, Stolzing A. Aging of Mesenchymal Stem Cells. *Ageing Res Rev* (2006) 5:91-116. doi: 10.1016/j.arr.2005.10.001

200. Fafian-Labora JA, Morente-Lopez M, Arufe MC. Effect of Aging on Behaviour of Mesenchymal Stem Cells. *World J Stem Cells* (2019) 11:337-46. doi: 10.4252/wjsc.v11.i6.337

201. Li Y, Wu Q, Wang Y, Li L, Bu H, Bao J. Senescence of Mesenchymal Stem Cells (Review). *Int J Mol Med* (2017) 39:775-82. doi: 10.3892/ijmm.2017.2912

202. Turinetto V, Vitale E, Giachino C. Senescence in Human Mesenchymal Stem Cells: Functional Changes and Implications in Stem Cell-Based Therapy. *Int J Mol Sci* (2016) 17(7):1164. doi: 10.3390/ijms17071164

203. Lepperdinger G. Inflammation and Mesenchymal Stem Cell Aging. *Curr Opin Immunol* (2011) 23:518-24. doi: 10.1016/j.coi.2011.05.007

204. Lunyak VV, Amaro-Ortiz A, Gaur M. Mesenchymal Stem Cells Secretory Responses: Senescence Messaging Secretome and Immunomodulation Perspective. *Front Genet* (2017) 8:220. doi: 10.3389/fgene.2017.00220

205. Malaise O, Tachikart Y, Constantinides M, Mumme M, Ferreira-Lopez R, Noack S, et al. Mesenchymal Stem Cell Senescence Alleviates Their Intrinsic and Seno-Suppressive Paracrine Properties Contributing to Osteoarthritis Development. *Aging (Albany NY)* (2019) 11:9128-46. doi: 10.18632/aging.102379

206. Vono R, Jover Garcia E, Spinetti G, Madeddu P. Oxidative Stress in Mesenchymal Stem Cell Senescence: Regulation by Coding and Noncoding Rnas. *Antioxid Redox Signal* (2018) 29:864-79. doi: 10.1089/ars.2017.7294

207. Ho YH, Del Toro R, Rivera-Torres J, Rak J, Korn C, Garcia-Garcia A, et al. Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion During Premature or Physiological Aging. *Cell Stem Cell* (2019) 25:407-418 e406. doi: 10.1016/j stems.2019.06.007

208. Collins JA, Diekman BO, Loeser RF. Targeting Aging for Disease Modification in Osteoarthritis. *Curr Opin Rheumatol* (2018) 30:101-7. doi: 10.1097/BOR.0000000000000456

209. Greene MA, Loeser RF. Aging-related Inflammation in Osteoarthritis. *Osteoarthritis Cartilage* (2015) 23:1966-71. doi: 10.1016/j.joca.2015.01.008

210. Ebersole JL, Graves CL, Gonzalez OA, Dawson D,3, Morford LA, Huja PE, et al. Aging, Inflammation, Immunity and Periodontal Disease. *Periodontol 2000* (2016) 72:54-75. doi: 10.1111/prd.12135

211. Halim M, Halim A. The Effects of Inflammation, Aging and Oxidative Stress on the Pathogenesis of Diabetes Mellitus (Type 2 Diabetes). *Diabetes Metab Syndr* (2019) 13:1165-72. doi: 10.1016/j dsx.2019.01.040

212. Lo Furno D, Mannino G, Giuffrida R. Functional Role of Mesenchymal Stem Cells in the Treatment of Chronic Neurodegenerative Diseases. *J Cell Physiol* (2018) 233:3982-99. doi: 10.1002/jcp.26192

213. Staff NP, Jones DT, Singer W. Mesenchymal Stromal Cell Therapies for Neurodegenerative Diseases. *Mayo Clin Proc* (2019) 94:892-905. doi: 10.1016/j.mayocp.2019.01.001

214. Oliva AA, McClain-Moss L, Pena A, Drouillard A, Hare JM. Allogeneic Mesenchymal Stem Cell Therapy: A Regenerative Medicine Approach to Geroscience. *Aging Med (Milton)* (2019) 2:142-6. doi: 10.1002/agm2.12079

215. Han X, Wang R, Zhou Y, Fei L, Sun H, Lai S, et al. Mapping the Mouse Cell Atlas by Microwell-Seq. *Cell* (2018) 172:1091-1107 e1017. doi: 10.1016/j.cell.2018.02.001

216. Chen G, Yung R. Meta-Inflammating At the Crossroad of Geroscience. *Aging Med (Milton)* (2019) 2:157-61. doi: 10.1002/agm2.12078

**Conflict of Interest:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Planat-Benard, Varin and Casteilla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.