Effect of aging on behaviour of mesenchymal stem cells
|
摘要
Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives(chondrocytes,osteocytes, adipocytes). This subpopulation of adult stem cells, called"mesenchymal stem cells" or "mesenchymal stromal cells(MSCs)", contributes directly to the homeostatic maintenance of their organs; hence, their senescence could be very deleterious for human bodily functions. MSCs are easily isolated and amenable their expansion in vitro because of the research demanding to test them in many diverse clinical indications. All of these works are shown by the rapidly expanding literature that includes many in vivo animal models. We do not have an in-depth understanding of mechanisms that induce cellular senescence, and to further clarify the consequences of the senescence process in MSCs, some hints may be derived from the study of cellular behaviour in vivo and in vitro, autophagy, mitochondrial stress and exosomal activity. In this particular work, we decided to review these biological features in the literature on MSC senescence over the last three years.
Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives(chondrocytes,osteocytes, adipocytes). This subpopulation of adult stem cells, called"mesenchymal stem cells" or "mesenchymal stromal cells(MSCs)", contributes directly to the homeostatic maintenance of their organs; hence, their senescence could be very deleterious for human bodily functions. MSCs are easily isolated and amenable their expansion in vitro because of the research demanding to test them in many diverse clinical indications. All of these works are shown by the rapidly expanding literature that includes many in vivo animal models. We do not have an in-depth understanding of mechanisms that induce cellular senescence, and to further clarify the consequences of the senescence process in MSCs, some hints may be derived from the study of cellular behaviour in vivo and in vitro, autophagy, mitochondrial stress and exosomal activity. In this particular work, we decided to review these biological features in the literature on MSC senescence over the last three years.
Organs whose source is the mesoderm lineage contain a subpopulation of stem cells that are able to differentiate among mesodermal derivatives(chondrocytes,osteocytes, adipocytes). This subpopulation of adult stem cells, called"mesenchymal stem cells" or "mesenchymal stromal cells(MSCs)", contributes directly to the homeostatic maintenance of their organs; hence, their senescence could be very deleterious for human bodily functions. MSCs are easily isolated and amenable their expansion in vitro because of the research demanding to test them in many diverse clinical indications. All of these works are shown by the rapidly expanding literature that includes many in vivo animal models. We do not have an in-depth understanding of mechanisms that induce cellular senescence, and to further clarify the consequences of the senescence process in MSCs, some hints may be derived from the study of cellular behaviour in vivo and in vitro, autophagy, mitochondrial stress and exosomal activity. In this particular work, we decided to review these biological features in the literature on MSC senescence over the last three years.
引文
1 Rando TA.Stem cells,ageing and the quest for immortality.Nature 2006;441:1080-1086[PMID:16810243 DOI:10.1038/nature04958]
2 Stab BR 2nd,Martinez L,Grismaldo A,Lerma A,Gutiérrez ML,Barrera LA,Sutachan JJ,Albarracín SL.Mitochondrial Functional Changes Characterization in Young and Senescent Human Adipose Derived MSCs.Front Aging Neurosci 2016;8:299[PMID:28018212 DOI:10.3389/fnagi.2016.00299]
3 Zhang M,Du Y,Lu R,Shu Y,Zhao W,Li Z,Zhang Y,Liu R,Yang T,Luo S,Gao M,Zhang Y,Zhang G,Liu J,Lu Y.Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21 Cip1/Waf1 Pathway.Oxid Med Cell Longev 2016;2016:7524308[PMID:27703600 DOI:10.1155/2016/7524308]
4 Lee JY,Yu KR,Lee BC,Kang I,Kim JJ,Jung EJ,Kim HS,Seo Y,Choi SW,Kang KS.GATA4-dependent regulation of the secretory phenotype via MCP-1 underlies lamin A-mediated human mesenchymal stem cell aging.Exp Mol Med 2018;50:63[PMID:29760459 DOI:10.1038/s12276-018-0092-3]
5 ?zcan S,Alessio N,Acar MB,Toprak G,G?nen ZB,Peluso G,Galderisi U.Myeloma cells can corrupt senescent mesenchymal stromal cells and impair their anti-tumor activity.Oncotarget 2015;6:39482-39492[PMID:26498687 DOI:10.18632/oncotarget.5430]
6 Kim HN,Chang J,Shao L,Han L,Iyer S,Manolagas SC,O'Brien CA,Jilka RL,Zhou D,Almeida M.DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age.Aging Cell 2017;16:693-703[PMID:28401730 DOI:10.1111/acel.12597]
7 Lazzarini R,Nicolai M,Pirani V,Mariotti C,Di Primio R.Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells.Aging(Albany NY)2018;10:3173-3184[PMID:30444724 DOI:10.18632/aging.101624]
8 Severino V,Alessio N,Farina A,Sandomenico A,Cipollaro M,Peluso G,Galderisi U,Chambery A.Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells.Cell Death Dis 2013;4:e911[PMID:24201810 DOI:10.1038/cddis.2013.445]
9 Vassilieva IO,Reshetnikova GF,Shatrova AN,Tsupkina NV,Kharchenko MV,Alekseenko LL,Nikolsky NN,Burova EB.Senescence-messaging secretome factors trigger premature senescence in human endometrium-derived stem cells.Biochem Biophys Res Commun 2018;496:1162-1168[PMID:29397942DOI:10.1016/j.bbrc.2018.01.163]
10 Madsen SD,Russell KC,Tucker HA,Glowacki J,Bunnell BA,O'Connor KC.Decoy TRAIL receptor CD264:a cell surface marker of cellular aging for human bone marrow-derived mesenchymal stem cells.Stem Cell Res Ther 2017;8:201[PMID:28962588 DOI:10.1186/s13287-017-0649-4]
11 Amati E,Perbellini O,Rotta G,Bernardi M,Chieregato K,Sella S,Rodeghiero F,Ruggeri M,Astori G.High-throughput immunophenotypic characterization of bone marrow-and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers:identification of angiotensin-converting enzyme(CD143)as a marker differentially expressed between adult and perinatal tissue sources.Stem Cell Res Ther 2018;9:10[PMID:29338788 DOI:10.1186/s13287-017-0755-3]
12 de Witte SFH,Lambert EE,Merino A,Strini T,Douben HJCW,O'Flynn L,Elliman SJ,de Klein AJEMM,Newsome PN,Baan CC,Hoogduijn MJ.Aging of bone marrow-and umbilical cord-derived mesenchymal stromal cells during expansion.Cytotherapy 2017;19:798-807[PMID:28462821 DOI:10.1016/j.jcyt.2017.03.071]
13 Fafián-Labora J,Lesende-Rodriguez I,Fernández-Pernas P,Sangiao-Alvarellos S,Monserrat L,Arntz OJ,van de Loo FJ,Mateos J,Arufe MC.Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles.Sci Rep 2017;7:43923[PMID:28262816 DOI:10.1038/srep43923]
14 Ganguly P,El-Jawhari JJ,Giannoudis PV,Burska AN,Ponchel F,Jones EA.Age-related Changes in Bone Marrow Mesenchymal Stromal Cells:A Potential Impact on Osteoporosis and Osteoarthritis Development.Cell Transplant 2017;26:1520-1529[PMID:29113463 DOI:10.1177/0963689717721201]
15 Ucer S,Iyer S,Kim HN,Han L,Rutlen C,Allison K,Thostenson JD,de Cabo R,Jilka RL,O'Brien C,Almeida M,Manolagas SC.The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are Independent and Mechanistically Distinct.J Bone Miner Res 2017;32:560-574[PMID:27714847 DOI:10.1002/jbmr.3014]
16 Xing Y,Zhang Y,Wu X,Zhao B,Ji Y,Xu X.A comprehensive study on donor-matched comparisons of three types of mesenchymal stem cells-containing cells from human dental tissue.J Periodontal Res 2019;54:286-299[PMID:30474138 DOI:10.1111/jre.12630]
17 Fafián-Labora J,Fernández-Pernas P,Fuentes I,De Toro J,Oreiro N,Sangiao-Alvarellos S,Mateos J,Arufe MC.Influence of age on rat bone-marrow mesenchymal stem cells potential.Sci Rep 2015;5:16765[PMID:26581954 DOI:10.1038/srep16765]
18 LeBlon CE,Casey ME,Fodor CR,Zhang T,Zhang X,Jedlicka SS.Correlation between in vitro expansion-related cell stiffening and differentiation potential of human mesenchymal stem cells.Differentiation 2015;90:1-15[PMID:26381795 DOI:10.1016/j.diff.2015.08.002]
19 Abolhasani M,Rezaee MA,Mohammadi M,Ghadimi T,Mohammadi M,Rahmani MR.Immunomodulatory properties of umbilical cord vein mesenchymal stromal cells influenced by gestational age and in vitro expansion.Immunol Lett 2018;194:62-68[PMID:29175314 DOI:10.1016/j.imlet.2017.11.008]
20 Twine NA,Harkness L,Adjaye J,Aldahmash A,Wilkins MR,Kassem M.Molecular Phenotyping of Telomerized Human Bone Marrow Skeletal Stem Cells Reveals a Genetic Program of Enhanced Proliferation and Maintenance of Differentiation Responses.JBMR Plus 2018;2:257-267[PMID:30283907 DOI:10.1002/jbm4.10050]
21 Kouroupis D,Churchman SM,McGonagle D,Jones EA.The assessment of CD146-based cell sorting and telomere length analysis for establishing the identity of mesenchymal stem cells in human umbilical cord.F1000Res 2014;3:126[PMID:25232467 DOI:10.12688/f1000research.4260.2]
22 Lu Y,Qu H,Qi D,Xu W,Liu S,Jin X,Song P,Guo Y,Jia Y,Wang X,Li H,Li Y,Quan C.OCT4maintains self-renewal and reverses senescence in human hair follicle mesenchymal stem cells through the downregulation of p21 by DNA methyltransferases.Stem Cell Res Ther 2019;10:28[PMID:30646941DOI:10.1186/s13287-018-1120-x]
23 Chen Y,Wei G,Xia H,Yu H,Tang Q,Bi F.Down regulation of lincRNA-p21 contributes to gastric cancer development through Hippo-independent activation of YAP.Oncotarget 2017;8:63813-63824[PMID:28969031 DOI:10.18632/oncotarget.19130]
24 Musavi M,Kohram F,Abasi M,Bolandi Z,Ajoudanian M,Mohammadi-Yeganeh S,Hashemi SM,Sharifi K,Fathi HR,Ghanbarian H.Rn7SK small nuclear RNA is involved in cellular senescence.J Cell Physiol 2019[PMID:30637716 DOI:10.1002/jcp.28119]
25 Monacelli F,Acquarone E,Giannotti C,Borghi R,Nencioni A.Vitamin C,Aging and Alzheimer's Disease.Nutrients 2017;9:pii:E670[PMID:28654021 DOI:10.3390/nu9070670]
26 Pirmoradi S,Fathi E,Farahzadi R,Pilehvar-Soltanahmadi Y,Zarghami N.Curcumin Affects Adipose Tissue-Derived Mesenchymal Stem Cell Aging Through TERT Gene Expression.Drug Res(Stuttg)2018;68:213-221[PMID:29017189 DOI:10.1055/s-0043-119635]
27 Baar MP,Brandt RMC,Putavet DA,Klein JDD,Derks KWJ,Bourgeois BRM,Stryeck S,Rijksen Y,van Willigenburg H,Feijtel DA,van der Pluijm I,Essers J,van Cappellen WA,van IJcken WF,Houtsmuller AB,Pothof J,de Bruin RWF,Madl T,Hoeijmakers JHJ,Campisi J,de Keizer PLJ.Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.Cell 2017;169:132-147.e16[PMID:28340339 DOI:10.1016/j.cell.2017.02.031]
28 Grezella C,Fernandez-Rebollo E,Franzen J,Ventura Ferreira MS,Beier F,Wagner W.Effects of senolytic drugs on human mesenchymal stromal cells.Stem Cell Res Ther 2018;9:108[PMID:29669575DOI:10.1186/s13287-018-0857-6]
29 Geng L,Liu Z,Zhang W,Li W,Wu Z,Wang W,Ren R,Su Y,Wang P,Sun L,Ju Z,Chan P,Song M,Qu J,Liu GH.Chemical screen identifies a geroprotective role of quercetin in premature aging.Protein Cell2018[PMID:30069858 DOI:10.1007/s13238-018-0567-y]
30 Hisamatsu D,Ohno-Oishi M,Nakamura S,Mabuchi Y,Naka-Kaneda H.Growth differentiation factor 6derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues.Aging(Albany NY)2016;8:1259-1275[PMID:27311402 DOI:10.18632/aging.100982]
31 Yin Y,Wu RX,He XT,Xu XY,Wang J,Chen FM.Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture.Stem Cell Res Ther 2017;8:153[PMID:28646912DOI:10.1186/s13287-017-0608-0]
32 Wang B,Lee WY,Huang B,Zhang JF,Wu T,Jiang X,Wang CC,Li G.Secretome of Human Fetal Mesenchymal Stem Cell Ameliorates Replicative Senescen.Stem Cells Dev 2016;25:1755-1766[PMID:27539404 DOI:10.1089/scd.2016.0079]
33 Kim YJ,Seo DH,Lee SH,Lee SH,An GH,Ahn HJ,Kwon D,Seo KW,Kang KS.Conditioned media from human umbilical cord blood-derived mesenchymal stem cells stimulate rejuvenation function in human skin.Biochem Biophys Rep 2018;16:96-102[PMID:30417126 DOI:10.1016/j.bbrep.2018.10.007]
34 Lei L,Su J,Chen J,Chen W,Chen X,Peng C.The role of lysophosphatidic acid in the physiology and pathology of the skin.Life Sci 2019;220:194-200[PMID:30584899 DOI:10.1016/j.lfs.2018.12.040]
35 Kanehira M,Fujiwara T,Nakajima S,Okitsu Y,Onishi Y,Fukuhara N,Ichinohasama R,Okada Y,Harigae H.An Lysophosphatidic Acid Receptors 1 and 3 Axis Governs Cellular Senescence of Mesenchymal Stromal Cells and Promotes Growth and Vascularization of Multiple Myeloma.Stem Cells2017;35:739-753[PMID:27641212 DOI:10.1002/stem.2499]
36 Fan J,An X,Yang Y,Xu H,Fan L,Deng L,Li T,Weng X,Zhang J,Chunhua Zhao R.MiR-1292 Targets FZD4 to Regulate Senescence and Osteogenic Differentiation of Stem Cells in TE/SJ/Mesenchymal Tissue System via the Wnt/β-catenin Pathway.Aging Dis 2018;9:1103-1121[PMID:30574422 DOI:10.14336/AD.2018.1110]
37 Liu W,Qi M,Konermann A,Zhang L,Jin F,Jin Y.The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells.Aging(Albany NY)2015;7:205-218[PMID:25855145 DOI:10.18632/aging.100728]
38 Dong J,Zhang Z,Huang H,Mo P,Cheng C,Liu J,Huang W,Tian C,Zhang C,Li J.miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4.Stem Cell Res Ther 2018;9:151[PMID:29848383 DOI:10.1186/s13287-018-0895-0]
39 Zhang T,Wang P,Liu Y,Zhou J,Shi Z,Cheng K,Huang T,Wang X,Yang GL,Yang B,Ma S,Guan F.Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo.Cell Tissue Res 2018;373:379-393[PMID:29500491 DOI:10.1007/s00441-018-2815-0]
40 Xu R,Fu Z,Liu X,Xiao T,Zhang P,Du Y,Yuan H,Cheng J,Jiang H.Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.Exp Gerontol 2016;84:71-79[PMID:27599698 DOI:10.1016/j.exger.2016.09.001]
41 Roux C,Saviane G,Pini J,Bela?d N,Dhib G,Voha C,Ibá?ez L,Boutin A,Mazure NM,Wakkach A,Blin-Wakkach C,Rouleau M.Immunosuppressive Mesenchymal Stromal Cells Derived from HumanInduced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo.Front Immunol2018;8:1991[PMID:29422893 DOI:10.3389/fimmu.2017.01991]
42 Wang LT,Jiang SS,Ting CH,Hsu PJ,Chang CC,Sytwu HK,Liu KJ,Yen BL.Differentiation of Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells Results in Downregulation of cMyc and DNA Replication Pathways with Immunomodulation Toward CD4 and CD8 Cells.Stem Cells2018;36:903-914[PMID:29396902 DOI:10.1002/stem.2795]
43 Zheng Y,Lei Y,Hu C,Hu C.p53 regulates autophagic activity in senescent rat mesenchymal stromal cells.Exp Gerontol 2016;75:64-71[PMID:26792455 DOI:10.1016/j.exger.2016.01.004]
44 Borodkina AV,Shatrova AN,Deryabin PI,Grukova AA,Nikolsky NN,Burova EB.Tetraploidization or autophagy:The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.Cell Cycle 2016;15:117-127[PMID:26636375 DOI:10.1080/15384101.2015.1121326]
45 Falser N,Bandtlow I,Rziha HJ,Haus M,Wolf H.The role of acute and latent virus infections in the pathogenesis of inner ear disturbances.Am J Otol 1987;8:136-147[PMID:3035932 DOI:10.1016/S0196-0709(87)80034-0]
46 Brunk UT,Terman A.The mitochondrial-lysosomal axis theory of aging:accumulation of damaged mitochondria as a result of imperfect autophagocytosis.Eur J Biochem 2002;269:1996-2002[PMID:11985575 DOI:10.1046/j.1432-1033.2002.02869.x]
47 Dicarlo M,Teti G,Iezzi I,Cerqueni G,Manzotti S,Falconi M,Mattioli-Belmonte M.Detecting senescent fate in mesenchymal stem cells:a combined cytofluorimetric and ultrastructural approach.Biogerontology2018;19:401-414[PMID:30101381 DOI:10.1007/s10522-018-9766-4]
48 Zecchini S,Giovarelli M,Perrotta C,Morisi F,Touvier T,Di Renzo I,Moscheni C,Bassi MT,Cervia D,Sandri M,Clementi E,De Palma C.Autophagy controls neonatal myogenesis by regulating the GH-IGF1system through a NFE2L2-and DDIT3-mediated mechanism.Autophagy 2019;15:58-77[PMID:30081710 DOI:10.1080/15548627.2018.1507439]
49 Capasso S,Alessio N,Squillaro T,Di Bernardo G,Melone MA,Cipollaro M,Peluso G,Galderisi U.Changes in autophagy,proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells.Oncotarget 2015;6:39457-39468[PMID:26540573 DOI:10.18632/oncotarget.6277]
50 Zhao K,Hao H,Liu J,Tong C,Cheng Y,Xie Z,Zang L,Mu Y,Han W.Bone marrow-derived mesenchymal stem cells ameliorate chronic high glucose-inducedβ-cell injury through modulation of autophagy.Cell Death Dis 2015;6:e1885[PMID:26379190 DOI:10.1038/cddis.2015.230]
51 Chang TC,Hsu MF,Wu KK.High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy.PLoS One 2015;10:e0126537[PMID:25961745 DOI:10.1371/journal.pone.0126537]
52 Bárcena C,López-Otín C,Kroemer G.Methionine restriction for improving progeria:another autophagyinducing anti-aging strategy?Autophagy 2019;15:558-559[PMID:30304972 DOI:10.1080/15548627.2018.1533059]
53 Alessio N,Del Gaudio S,Capasso S,Di Bernardo G,Cappabianca S,Cipollaro M,Peluso G,Galderisi U.Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.Oncotarget 2015;6:8155-8166[PMID:25544750 DOI:10.18632/oncotarget.2692]
54 Ma Y,Qi M,An Y,Zhang L,Yang R,Doro DH,Liu W,Jin Y.Autophagy controls mesenchymal stem cell properties and senescence during bone aging.Aging Cell 2018;17[PMID:29210174 DOI:10.1111/acel.12709]
55 Wan Y,Zhuo N,Li Y,Zhao W,Jiang D.Autophagy promotes osteogenic differentiation of human bone marrow mesenchymal stem cell derived from osteoporotic vertebrae.Biochem Biophys Res Commun 2017;488:46-52[PMID:28476617 DOI:10.1016/j.bbrc.2017.05.004]
56 Squillaro T,Antonucci I,Alessio N,Esposito A,Cipollaro M,Melone MAB,Peluso G,Stuppia L,Galderisi U.Impact of lysosomal storage disorders on biology of mesenchymal stem cells:Evidences from in vitro silencing of glucocerebrosidase(GBA)and alpha-galactosidase A(GLA)enzymes.J Cell Physiol2017;232:3454-3467[PMID:28098348 DOI:10.1002/jcp.25807]
57 Wang L,Han X,Qu G,Su L,Zhao B,Miao J.A pH probe inhibits senescence in mesenchymal stem cells.Stem Cell Res Ther 2018;9:343[PMID:30526663 DOI:10.1186/s13287-018-1081-0]
58 Yang M,Wen T,Chen H,Deng J,Yang C,Zhang Z.Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs:role of autophagy.Stem Cell Res Ther 2018;9:284[PMID:30359321 DOI:10.1186/s13287-018-1028-5]
59 Yun SP,Han YS,Lee JH,Kim SM,Lee SH.Melatonin Rescues Mesenchymal Stem Cells from Senescence Induced by the Uremic Toxin p-Cresol via Inhibiting mTOR-Dependent Autophagy.Biomol Ther(Seoul)2018;26:389-398[PMID:28655071 DOI:10.4062/biomolther.2017.071]
60 Denu RA,Hematti P.Effects of Oxidative Stress on Mesenchymal Stem Cell Biology.Oxid Med Cell Longev 2016;2016:2989076[PMID:27413419 DOI:10.1155/2016/2989076]
61 ScialòF,Fernández-Ayala DJ,Sanz A.Role of Mitochondrial Reverse Electron Transport in ROSSignaling:Potential Roles in Health and Disease.Front Physiol 2017;8:428[PMID:28701960 DOI:10.3389/fphys.2017.00428]
62 Marycz K,Kornicka K,Basinska K,Czyrek A.Equine Metabolic Syndrome Affects Viability,Senescence,and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells:New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging.Oxid Med Cell Longev2016;2016:4710326[PMID:26682006 DOI:10.1155/2016/4710326]
63 Marycz K,Kornicka K,Mar?dziak M,Golonka P,NicpońJ.Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.J Cell Mol Med 2016;20:2384-2404[PMID:27629697 DOI:10.1111/jcmm.12932]
64 Deschênes-Simard X,Parisotto M,Rowell MC,Le CalvéB,Igelmann S,Moineau-Vallée K,SaintGermain E,Kalegari P,Bourdeau V,Kottakis F,Bardeesy N,Ferbeyre G.Circumventing senescence is associated with stem cell properties and metformin sensitivity.Aging Cell 2019;18:e12889[PMID:30614183 DOI:10.1111/acel.12889]
65 Khanh VC,Zulkifli AF,Tokunaga C,Yamashita T,Hiramatsu Y,Ohneda O.Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1.Biochem Biophys Res Commun 2018;500:682-690[PMID:29678576 DOI:10.1016/j.bbrc.2018.04.136]
66 Huang T,Liu R,Fu X,Yao D,Yang M,Liu Q,Lu WW,Wu C,Guan M.Aging Reduces an ERRalphaDirected Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.Stem Cells 2017;35:411-424[PMID:27501743 DOI:10.1002/stem.2470]
67 Shuai Y,Liao L,Su X,Yu Y,Shao B,Jing H,Zhang X,Deng Z,Jin Y.Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion.Theranostics 2016;6:1899-1917[PMID:27570559 DOI:10.7150/thno.15412]
68 Fang J,Yan Y,Teng X,Wen X,Li N,Peng S,Liu W,Donadeu FX,Zhao S,Hua J.Melatonin prevents senescence of canine adipose-derived mesenchymal stem cells through activating NRF2 and inhibiting ERstress.Aging(Albany NY)2018;10:2954-2972[PMID:30362962 DOI:10.18632/aging.101602]
69 Xie Z,Jones A,Deeney JT,Hur SK,Bankaitis VA.Inborn Errors of Long-Chain Fatty Acidβ-Oxidation Link Neural Stem Cell Self-Renewal to Autism.Cell Rep 2016;14:991-999[PMID:26832401 DOI:10.1016/j.celrep.2016.01.004]
70 Farahzadi R,Fathi E,Mesbah-Namin SA,Zarghami N.Anti-aging protective effect of L-carnitine as clinical agent in regenerative medicine through increasing telomerase activity and change in the hTERTpromoter CpG island methylation status of adipose tissue-derived mesenchymal stem cells.Tissue Cell2018;54:105-113[PMID:30309499 DOI:10.1016/j.tice.2018.08.012]
71 Oh JY,Choi GE,Lee HJ,Jung YH,Chae CW,Kim JS,Lee CK,Han HJ.17β-Estradiol protects mesenchymal stem cells against high glucose-induced mitochondrial oxidants production via Nrf2/Sirt3/MnSOD signaling.Free Radic Biol Med 2019;130:328-342[PMID:30412732 DOI:10.1016/j.freeradbiomed.2018.11.003]
72 Denu RA.SIRT3 Enhances Mesenchymal Stem Cell Longevity and Differentiation.Oxid Med Cell Longev 2017;2017:5841716[PMID:28717408 DOI:10.1155/2017/5841716]
73 Lombard DB,Alt FW,Cheng HL,Bunkenborg J,Streeper RS,Mostoslavsky R,Kim J,Yancopoulos G,Valenzuela D,Murphy A,Yang Y,Chen Y,Hirschey MD,Bronson RT,Haigis M,Guarente LP,Farese RV,Weissman S,Verdin E,Schwer B.Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation.Mol Cell Biol 2007;27:8807-8814[PMID:17923681 DOI:10.1128/MCB.01636-07]
74 Yao J,Zheng J,Cai J,Zeng K,Zhou C,Zhang J,Li S,Li H,Chen L,He L,Chen H,Fu H,Zhang Q,Chen G,Yang Y,Zhang Y.Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response.FASEB J 2019;33:1695-1710[PMID:30226809 DOI:10.1096/fj.201800131RR]
75 Tofi?o-Vian M,Guillén MI,Pérez Del Caz MD,Castejón MA,Alcaraz MJ.Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts.Oxid Med Cell Longev 2017;2017:7197598[PMID:29230269 DOI:10.1155/2017/7197598]
76 Xu M,Bradley EW,Weivoda MM,Hwang SM,Pirtskhalava T,Decklever T,Curran GL,Ogrodnik M,Jurk D,Johnson KO,Lowe V,Tchkonia T,Westendorf JJ,Kirkland JL.Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice.J Gerontol A Biol Sci Med Sci 2017;72:780-785[PMID:27516624 DOI:10.1093/gerona/glw154]
77 McCulloch K,Litherland GJ,Rai TS.Cellular senescence in osteoarthritis pathology.Aging Cell 2017;16:210-218[PMID:28124466 DOI:10.1111/acel.12562]
78 Platas J,Guillén MI,Pérez Del Caz MD,Gomar F,Castejón MA,Mirabet V,Alcaraz MJ.Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes.Aging(Albany NY)2016;8:1703-1717[PMID:27490266 DOI:10.18632/aging.101007]
79 Bebelman MP,Smit MJ,Pegtel DM,Baglio SR.Biogenesis and function of extracellular vesicles in cancer.Pharmacol Ther 2018;188:1-11[PMID:29476772 DOI:10.1016/j.pharmthera.2018.02.013]
80 Phinney DG,Pittenger MF.Concise Review:MSC-Derived Exosomes for Cell-Free Therapy.Stem Cells2017;35:851-858[PMID:28294454 DOI:10.1002/stem.2575]
81 Lin S,Zhu B,Huang G,Zeng Q,Wang C.Microvesicles derived from human bone marrow mesenchymal stem cells promote U2OS cell growth under hypoxia:the role of PI3K/AKT and HIF-1α.Hum Cell 2019;32:64-74[PMID:30506278 DOI:10.1007/s13577-018-0224-z]
82 Zhu Z,Zhang Y,Zhang Y,Zhang H,Liu W,Zhang N,Zhang X,Zhou G,Wu L,Hua K,Ding J.Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAs in vitro.Hum Reprod 2019;34:248-260[PMID:30576496 DOI:10.1093/humrep/dey344]
83 Kulkarni R,Bajaj M,Ghode S,Jalnapurkar S,Limaye L,Kale VP.Intercellular Transfer of Microvesicles from Young Mesenchymal Stromal Cells Rejuvenates Aged Murine Hematopoietic Stem Cells.Stem Cells2018;36:420-433[PMID:29230885 DOI:10.1002/stem.2756]
84 Khayrullin A,Krishnan P,Martinez-Nater L,Mendhe B,Fulzele S,Liu Y,Mattison JA,Hamrick MW.Very Long-Chain C24:1 Ceramide Is Increased in Serum Extracellular Vesicles with Aging and Can Induce Senescence in Bone-Derived Mesenchymal Stem Cells.Cells 2019;8:pii:E37[PMID:30634626DOI:10.3390/cells8010037]
2 Stab BR 2nd,Martinez L,Grismaldo A,Lerma A,Gutiérrez ML,Barrera LA,Sutachan JJ,Albarracín SL.Mitochondrial Functional Changes Characterization in Young and Senescent Human Adipose Derived MSCs.Front Aging Neurosci 2016;8:299[PMID:28018212 DOI:10.3389/fnagi.2016.00299]
3 Zhang M,Du Y,Lu R,Shu Y,Zhao W,Li Z,Zhang Y,Liu R,Yang T,Luo S,Gao M,Zhang Y,Zhang G,Liu J,Lu Y.Cholesterol Retards Senescence in Bone Marrow Mesenchymal Stem Cells by Modulating Autophagy and ROS/p53/p21 Cip1/Waf1 Pathway.Oxid Med Cell Longev 2016;2016:7524308[PMID:27703600 DOI:10.1155/2016/7524308]
4 Lee JY,Yu KR,Lee BC,Kang I,Kim JJ,Jung EJ,Kim HS,Seo Y,Choi SW,Kang KS.GATA4-dependent regulation of the secretory phenotype via MCP-1 underlies lamin A-mediated human mesenchymal stem cell aging.Exp Mol Med 2018;50:63[PMID:29760459 DOI:10.1038/s12276-018-0092-3]
5 ?zcan S,Alessio N,Acar MB,Toprak G,G?nen ZB,Peluso G,Galderisi U.Myeloma cells can corrupt senescent mesenchymal stromal cells and impair their anti-tumor activity.Oncotarget 2015;6:39482-39492[PMID:26498687 DOI:10.18632/oncotarget.5430]
6 Kim HN,Chang J,Shao L,Han L,Iyer S,Manolagas SC,O'Brien CA,Jilka RL,Zhou D,Almeida M.DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age.Aging Cell 2017;16:693-703[PMID:28401730 DOI:10.1111/acel.12597]
7 Lazzarini R,Nicolai M,Pirani V,Mariotti C,Di Primio R.Effects of senescent secretory phenotype acquisition on human retinal pigment epithelial stem cells.Aging(Albany NY)2018;10:3173-3184[PMID:30444724 DOI:10.18632/aging.101624]
8 Severino V,Alessio N,Farina A,Sandomenico A,Cipollaro M,Peluso G,Galderisi U,Chambery A.Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells.Cell Death Dis 2013;4:e911[PMID:24201810 DOI:10.1038/cddis.2013.445]
9 Vassilieva IO,Reshetnikova GF,Shatrova AN,Tsupkina NV,Kharchenko MV,Alekseenko LL,Nikolsky NN,Burova EB.Senescence-messaging secretome factors trigger premature senescence in human endometrium-derived stem cells.Biochem Biophys Res Commun 2018;496:1162-1168[PMID:29397942DOI:10.1016/j.bbrc.2018.01.163]
10 Madsen SD,Russell KC,Tucker HA,Glowacki J,Bunnell BA,O'Connor KC.Decoy TRAIL receptor CD264:a cell surface marker of cellular aging for human bone marrow-derived mesenchymal stem cells.Stem Cell Res Ther 2017;8:201[PMID:28962588 DOI:10.1186/s13287-017-0649-4]
11 Amati E,Perbellini O,Rotta G,Bernardi M,Chieregato K,Sella S,Rodeghiero F,Ruggeri M,Astori G.High-throughput immunophenotypic characterization of bone marrow-and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers:identification of angiotensin-converting enzyme(CD143)as a marker differentially expressed between adult and perinatal tissue sources.Stem Cell Res Ther 2018;9:10[PMID:29338788 DOI:10.1186/s13287-017-0755-3]
12 de Witte SFH,Lambert EE,Merino A,Strini T,Douben HJCW,O'Flynn L,Elliman SJ,de Klein AJEMM,Newsome PN,Baan CC,Hoogduijn MJ.Aging of bone marrow-and umbilical cord-derived mesenchymal stromal cells during expansion.Cytotherapy 2017;19:798-807[PMID:28462821 DOI:10.1016/j.jcyt.2017.03.071]
13 Fafián-Labora J,Lesende-Rodriguez I,Fernández-Pernas P,Sangiao-Alvarellos S,Monserrat L,Arntz OJ,van de Loo FJ,Mateos J,Arufe MC.Effect of age on pro-inflammatory miRNAs contained in mesenchymal stem cell-derived extracellular vesicles.Sci Rep 2017;7:43923[PMID:28262816 DOI:10.1038/srep43923]
14 Ganguly P,El-Jawhari JJ,Giannoudis PV,Burska AN,Ponchel F,Jones EA.Age-related Changes in Bone Marrow Mesenchymal Stromal Cells:A Potential Impact on Osteoporosis and Osteoarthritis Development.Cell Transplant 2017;26:1520-1529[PMID:29113463 DOI:10.1177/0963689717721201]
15 Ucer S,Iyer S,Kim HN,Han L,Rutlen C,Allison K,Thostenson JD,de Cabo R,Jilka RL,O'Brien C,Almeida M,Manolagas SC.The Effects of Aging and Sex Steroid Deficiency on the Murine Skeleton Are Independent and Mechanistically Distinct.J Bone Miner Res 2017;32:560-574[PMID:27714847 DOI:10.1002/jbmr.3014]
16 Xing Y,Zhang Y,Wu X,Zhao B,Ji Y,Xu X.A comprehensive study on donor-matched comparisons of three types of mesenchymal stem cells-containing cells from human dental tissue.J Periodontal Res 2019;54:286-299[PMID:30474138 DOI:10.1111/jre.12630]
17 Fafián-Labora J,Fernández-Pernas P,Fuentes I,De Toro J,Oreiro N,Sangiao-Alvarellos S,Mateos J,Arufe MC.Influence of age on rat bone-marrow mesenchymal stem cells potential.Sci Rep 2015;5:16765[PMID:26581954 DOI:10.1038/srep16765]
18 LeBlon CE,Casey ME,Fodor CR,Zhang T,Zhang X,Jedlicka SS.Correlation between in vitro expansion-related cell stiffening and differentiation potential of human mesenchymal stem cells.Differentiation 2015;90:1-15[PMID:26381795 DOI:10.1016/j.diff.2015.08.002]
19 Abolhasani M,Rezaee MA,Mohammadi M,Ghadimi T,Mohammadi M,Rahmani MR.Immunomodulatory properties of umbilical cord vein mesenchymal stromal cells influenced by gestational age and in vitro expansion.Immunol Lett 2018;194:62-68[PMID:29175314 DOI:10.1016/j.imlet.2017.11.008]
20 Twine NA,Harkness L,Adjaye J,Aldahmash A,Wilkins MR,Kassem M.Molecular Phenotyping of Telomerized Human Bone Marrow Skeletal Stem Cells Reveals a Genetic Program of Enhanced Proliferation and Maintenance of Differentiation Responses.JBMR Plus 2018;2:257-267[PMID:30283907 DOI:10.1002/jbm4.10050]
21 Kouroupis D,Churchman SM,McGonagle D,Jones EA.The assessment of CD146-based cell sorting and telomere length analysis for establishing the identity of mesenchymal stem cells in human umbilical cord.F1000Res 2014;3:126[PMID:25232467 DOI:10.12688/f1000research.4260.2]
22 Lu Y,Qu H,Qi D,Xu W,Liu S,Jin X,Song P,Guo Y,Jia Y,Wang X,Li H,Li Y,Quan C.OCT4maintains self-renewal and reverses senescence in human hair follicle mesenchymal stem cells through the downregulation of p21 by DNA methyltransferases.Stem Cell Res Ther 2019;10:28[PMID:30646941DOI:10.1186/s13287-018-1120-x]
23 Chen Y,Wei G,Xia H,Yu H,Tang Q,Bi F.Down regulation of lincRNA-p21 contributes to gastric cancer development through Hippo-independent activation of YAP.Oncotarget 2017;8:63813-63824[PMID:28969031 DOI:10.18632/oncotarget.19130]
24 Musavi M,Kohram F,Abasi M,Bolandi Z,Ajoudanian M,Mohammadi-Yeganeh S,Hashemi SM,Sharifi K,Fathi HR,Ghanbarian H.Rn7SK small nuclear RNA is involved in cellular senescence.J Cell Physiol 2019[PMID:30637716 DOI:10.1002/jcp.28119]
25 Monacelli F,Acquarone E,Giannotti C,Borghi R,Nencioni A.Vitamin C,Aging and Alzheimer's Disease.Nutrients 2017;9:pii:E670[PMID:28654021 DOI:10.3390/nu9070670]
26 Pirmoradi S,Fathi E,Farahzadi R,Pilehvar-Soltanahmadi Y,Zarghami N.Curcumin Affects Adipose Tissue-Derived Mesenchymal Stem Cell Aging Through TERT Gene Expression.Drug Res(Stuttg)2018;68:213-221[PMID:29017189 DOI:10.1055/s-0043-119635]
27 Baar MP,Brandt RMC,Putavet DA,Klein JDD,Derks KWJ,Bourgeois BRM,Stryeck S,Rijksen Y,van Willigenburg H,Feijtel DA,van der Pluijm I,Essers J,van Cappellen WA,van IJcken WF,Houtsmuller AB,Pothof J,de Bruin RWF,Madl T,Hoeijmakers JHJ,Campisi J,de Keizer PLJ.Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.Cell 2017;169:132-147.e16[PMID:28340339 DOI:10.1016/j.cell.2017.02.031]
28 Grezella C,Fernandez-Rebollo E,Franzen J,Ventura Ferreira MS,Beier F,Wagner W.Effects of senolytic drugs on human mesenchymal stromal cells.Stem Cell Res Ther 2018;9:108[PMID:29669575DOI:10.1186/s13287-018-0857-6]
29 Geng L,Liu Z,Zhang W,Li W,Wu Z,Wang W,Ren R,Su Y,Wang P,Sun L,Ju Z,Chan P,Song M,Qu J,Liu GH.Chemical screen identifies a geroprotective role of quercetin in premature aging.Protein Cell2018[PMID:30069858 DOI:10.1007/s13238-018-0567-y]
30 Hisamatsu D,Ohno-Oishi M,Nakamura S,Mabuchi Y,Naka-Kaneda H.Growth differentiation factor 6derived from mesenchymal stem/stromal cells reduces age-related functional deterioration in multiple tissues.Aging(Albany NY)2016;8:1259-1275[PMID:27311402 DOI:10.18632/aging.100982]
31 Yin Y,Wu RX,He XT,Xu XY,Wang J,Chen FM.Influences of age-related changes in mesenchymal stem cells on macrophages during in-vitro culture.Stem Cell Res Ther 2017;8:153[PMID:28646912DOI:10.1186/s13287-017-0608-0]
32 Wang B,Lee WY,Huang B,Zhang JF,Wu T,Jiang X,Wang CC,Li G.Secretome of Human Fetal Mesenchymal Stem Cell Ameliorates Replicative Senescen.Stem Cells Dev 2016;25:1755-1766[PMID:27539404 DOI:10.1089/scd.2016.0079]
33 Kim YJ,Seo DH,Lee SH,Lee SH,An GH,Ahn HJ,Kwon D,Seo KW,Kang KS.Conditioned media from human umbilical cord blood-derived mesenchymal stem cells stimulate rejuvenation function in human skin.Biochem Biophys Rep 2018;16:96-102[PMID:30417126 DOI:10.1016/j.bbrep.2018.10.007]
34 Lei L,Su J,Chen J,Chen W,Chen X,Peng C.The role of lysophosphatidic acid in the physiology and pathology of the skin.Life Sci 2019;220:194-200[PMID:30584899 DOI:10.1016/j.lfs.2018.12.040]
35 Kanehira M,Fujiwara T,Nakajima S,Okitsu Y,Onishi Y,Fukuhara N,Ichinohasama R,Okada Y,Harigae H.An Lysophosphatidic Acid Receptors 1 and 3 Axis Governs Cellular Senescence of Mesenchymal Stromal Cells and Promotes Growth and Vascularization of Multiple Myeloma.Stem Cells2017;35:739-753[PMID:27641212 DOI:10.1002/stem.2499]
36 Fan J,An X,Yang Y,Xu H,Fan L,Deng L,Li T,Weng X,Zhang J,Chunhua Zhao R.MiR-1292 Targets FZD4 to Regulate Senescence and Osteogenic Differentiation of Stem Cells in TE/SJ/Mesenchymal Tissue System via the Wnt/β-catenin Pathway.Aging Dis 2018;9:1103-1121[PMID:30574422 DOI:10.14336/AD.2018.1110]
37 Liu W,Qi M,Konermann A,Zhang L,Jin F,Jin Y.The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells.Aging(Albany NY)2015;7:205-218[PMID:25855145 DOI:10.18632/aging.100728]
38 Dong J,Zhang Z,Huang H,Mo P,Cheng C,Liu J,Huang W,Tian C,Zhang C,Li J.miR-10a rejuvenates aged human mesenchymal stem cells and improves heart function after myocardial infarction through KLF4.Stem Cell Res Ther 2018;9:151[PMID:29848383 DOI:10.1186/s13287-018-0895-0]
39 Zhang T,Wang P,Liu Y,Zhou J,Shi Z,Cheng K,Huang T,Wang X,Yang GL,Yang B,Ma S,Guan F.Overexpression of FOXQ1 enhances anti-senescence and migration effects of human umbilical cord mesenchymal stem cells in vitro and in vivo.Cell Tissue Res 2018;373:379-393[PMID:29500491 DOI:10.1007/s00441-018-2815-0]
40 Xu R,Fu Z,Liu X,Xiao T,Zhang P,Du Y,Yuan H,Cheng J,Jiang H.Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats.Exp Gerontol 2016;84:71-79[PMID:27599698 DOI:10.1016/j.exger.2016.09.001]
41 Roux C,Saviane G,Pini J,Bela?d N,Dhib G,Voha C,Ibá?ez L,Boutin A,Mazure NM,Wakkach A,Blin-Wakkach C,Rouleau M.Immunosuppressive Mesenchymal Stromal Cells Derived from HumanInduced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo.Front Immunol2018;8:1991[PMID:29422893 DOI:10.3389/fimmu.2017.01991]
42 Wang LT,Jiang SS,Ting CH,Hsu PJ,Chang CC,Sytwu HK,Liu KJ,Yen BL.Differentiation of Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells Results in Downregulation of cMyc and DNA Replication Pathways with Immunomodulation Toward CD4 and CD8 Cells.Stem Cells2018;36:903-914[PMID:29396902 DOI:10.1002/stem.2795]
43 Zheng Y,Lei Y,Hu C,Hu C.p53 regulates autophagic activity in senescent rat mesenchymal stromal cells.Exp Gerontol 2016;75:64-71[PMID:26792455 DOI:10.1016/j.exger.2016.01.004]
44 Borodkina AV,Shatrova AN,Deryabin PI,Grukova AA,Nikolsky NN,Burova EB.Tetraploidization or autophagy:The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.Cell Cycle 2016;15:117-127[PMID:26636375 DOI:10.1080/15384101.2015.1121326]
45 Falser N,Bandtlow I,Rziha HJ,Haus M,Wolf H.The role of acute and latent virus infections in the pathogenesis of inner ear disturbances.Am J Otol 1987;8:136-147[PMID:3035932 DOI:10.1016/S0196-0709(87)80034-0]
46 Brunk UT,Terman A.The mitochondrial-lysosomal axis theory of aging:accumulation of damaged mitochondria as a result of imperfect autophagocytosis.Eur J Biochem 2002;269:1996-2002[PMID:11985575 DOI:10.1046/j.1432-1033.2002.02869.x]
47 Dicarlo M,Teti G,Iezzi I,Cerqueni G,Manzotti S,Falconi M,Mattioli-Belmonte M.Detecting senescent fate in mesenchymal stem cells:a combined cytofluorimetric and ultrastructural approach.Biogerontology2018;19:401-414[PMID:30101381 DOI:10.1007/s10522-018-9766-4]
48 Zecchini S,Giovarelli M,Perrotta C,Morisi F,Touvier T,Di Renzo I,Moscheni C,Bassi MT,Cervia D,Sandri M,Clementi E,De Palma C.Autophagy controls neonatal myogenesis by regulating the GH-IGF1system through a NFE2L2-and DDIT3-mediated mechanism.Autophagy 2019;15:58-77[PMID:30081710 DOI:10.1080/15548627.2018.1507439]
49 Capasso S,Alessio N,Squillaro T,Di Bernardo G,Melone MA,Cipollaro M,Peluso G,Galderisi U.Changes in autophagy,proteasome activity and metabolism to determine a specific signature for acute and chronic senescent mesenchymal stromal cells.Oncotarget 2015;6:39457-39468[PMID:26540573 DOI:10.18632/oncotarget.6277]
50 Zhao K,Hao H,Liu J,Tong C,Cheng Y,Xie Z,Zang L,Mu Y,Han W.Bone marrow-derived mesenchymal stem cells ameliorate chronic high glucose-inducedβ-cell injury through modulation of autophagy.Cell Death Dis 2015;6:e1885[PMID:26379190 DOI:10.1038/cddis.2015.230]
51 Chang TC,Hsu MF,Wu KK.High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy.PLoS One 2015;10:e0126537[PMID:25961745 DOI:10.1371/journal.pone.0126537]
52 Bárcena C,López-Otín C,Kroemer G.Methionine restriction for improving progeria:another autophagyinducing anti-aging strategy?Autophagy 2019;15:558-559[PMID:30304972 DOI:10.1080/15548627.2018.1533059]
53 Alessio N,Del Gaudio S,Capasso S,Di Bernardo G,Cappabianca S,Cipollaro M,Peluso G,Galderisi U.Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.Oncotarget 2015;6:8155-8166[PMID:25544750 DOI:10.18632/oncotarget.2692]
54 Ma Y,Qi M,An Y,Zhang L,Yang R,Doro DH,Liu W,Jin Y.Autophagy controls mesenchymal stem cell properties and senescence during bone aging.Aging Cell 2018;17[PMID:29210174 DOI:10.1111/acel.12709]
55 Wan Y,Zhuo N,Li Y,Zhao W,Jiang D.Autophagy promotes osteogenic differentiation of human bone marrow mesenchymal stem cell derived from osteoporotic vertebrae.Biochem Biophys Res Commun 2017;488:46-52[PMID:28476617 DOI:10.1016/j.bbrc.2017.05.004]
56 Squillaro T,Antonucci I,Alessio N,Esposito A,Cipollaro M,Melone MAB,Peluso G,Stuppia L,Galderisi U.Impact of lysosomal storage disorders on biology of mesenchymal stem cells:Evidences from in vitro silencing of glucocerebrosidase(GBA)and alpha-galactosidase A(GLA)enzymes.J Cell Physiol2017;232:3454-3467[PMID:28098348 DOI:10.1002/jcp.25807]
57 Wang L,Han X,Qu G,Su L,Zhao B,Miao J.A pH probe inhibits senescence in mesenchymal stem cells.Stem Cell Res Ther 2018;9:343[PMID:30526663 DOI:10.1186/s13287-018-1081-0]
58 Yang M,Wen T,Chen H,Deng J,Yang C,Zhang Z.Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs:role of autophagy.Stem Cell Res Ther 2018;9:284[PMID:30359321 DOI:10.1186/s13287-018-1028-5]
59 Yun SP,Han YS,Lee JH,Kim SM,Lee SH.Melatonin Rescues Mesenchymal Stem Cells from Senescence Induced by the Uremic Toxin p-Cresol via Inhibiting mTOR-Dependent Autophagy.Biomol Ther(Seoul)2018;26:389-398[PMID:28655071 DOI:10.4062/biomolther.2017.071]
60 Denu RA,Hematti P.Effects of Oxidative Stress on Mesenchymal Stem Cell Biology.Oxid Med Cell Longev 2016;2016:2989076[PMID:27413419 DOI:10.1155/2016/2989076]
61 ScialòF,Fernández-Ayala DJ,Sanz A.Role of Mitochondrial Reverse Electron Transport in ROSSignaling:Potential Roles in Health and Disease.Front Physiol 2017;8:428[PMID:28701960 DOI:10.3389/fphys.2017.00428]
62 Marycz K,Kornicka K,Basinska K,Czyrek A.Equine Metabolic Syndrome Affects Viability,Senescence,and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells:New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging.Oxid Med Cell Longev2016;2016:4710326[PMID:26682006 DOI:10.1155/2016/4710326]
63 Marycz K,Kornicka K,Mar?dziak M,Golonka P,NicpońJ.Equine metabolic syndrome impairs adipose stem cells osteogenic differentiation by predominance of autophagy over selective mitophagy.J Cell Mol Med 2016;20:2384-2404[PMID:27629697 DOI:10.1111/jcmm.12932]
64 Deschênes-Simard X,Parisotto M,Rowell MC,Le CalvéB,Igelmann S,Moineau-Vallée K,SaintGermain E,Kalegari P,Bourdeau V,Kottakis F,Bardeesy N,Ferbeyre G.Circumventing senescence is associated with stem cell properties and metformin sensitivity.Aging Cell 2019;18:e12889[PMID:30614183 DOI:10.1111/acel.12889]
65 Khanh VC,Zulkifli AF,Tokunaga C,Yamashita T,Hiramatsu Y,Ohneda O.Aging impairs beige adipocyte differentiation of mesenchymal stem cells via the reduced expression of Sirtuin 1.Biochem Biophys Res Commun 2018;500:682-690[PMID:29678576 DOI:10.1016/j.bbrc.2018.04.136]
66 Huang T,Liu R,Fu X,Yao D,Yang M,Liu Q,Lu WW,Wu C,Guan M.Aging Reduces an ERRalphaDirected Mitochondrial Glutaminase Expression Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal Stem Cells.Stem Cells 2017;35:411-424[PMID:27501743 DOI:10.1002/stem.2470]
67 Shuai Y,Liao L,Su X,Yu Y,Shao B,Jing H,Zhang X,Deng Z,Jin Y.Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion.Theranostics 2016;6:1899-1917[PMID:27570559 DOI:10.7150/thno.15412]
68 Fang J,Yan Y,Teng X,Wen X,Li N,Peng S,Liu W,Donadeu FX,Zhao S,Hua J.Melatonin prevents senescence of canine adipose-derived mesenchymal stem cells through activating NRF2 and inhibiting ERstress.Aging(Albany NY)2018;10:2954-2972[PMID:30362962 DOI:10.18632/aging.101602]
69 Xie Z,Jones A,Deeney JT,Hur SK,Bankaitis VA.Inborn Errors of Long-Chain Fatty Acidβ-Oxidation Link Neural Stem Cell Self-Renewal to Autism.Cell Rep 2016;14:991-999[PMID:26832401 DOI:10.1016/j.celrep.2016.01.004]
70 Farahzadi R,Fathi E,Mesbah-Namin SA,Zarghami N.Anti-aging protective effect of L-carnitine as clinical agent in regenerative medicine through increasing telomerase activity and change in the hTERTpromoter CpG island methylation status of adipose tissue-derived mesenchymal stem cells.Tissue Cell2018;54:105-113[PMID:30309499 DOI:10.1016/j.tice.2018.08.012]
71 Oh JY,Choi GE,Lee HJ,Jung YH,Chae CW,Kim JS,Lee CK,Han HJ.17β-Estradiol protects mesenchymal stem cells against high glucose-induced mitochondrial oxidants production via Nrf2/Sirt3/MnSOD signaling.Free Radic Biol Med 2019;130:328-342[PMID:30412732 DOI:10.1016/j.freeradbiomed.2018.11.003]
72 Denu RA.SIRT3 Enhances Mesenchymal Stem Cell Longevity and Differentiation.Oxid Med Cell Longev 2017;2017:5841716[PMID:28717408 DOI:10.1155/2017/5841716]
73 Lombard DB,Alt FW,Cheng HL,Bunkenborg J,Streeper RS,Mostoslavsky R,Kim J,Yancopoulos G,Valenzuela D,Murphy A,Yang Y,Chen Y,Hirschey MD,Bronson RT,Haigis M,Guarente LP,Farese RV,Weissman S,Verdin E,Schwer B.Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation.Mol Cell Biol 2007;27:8807-8814[PMID:17923681 DOI:10.1128/MCB.01636-07]
74 Yao J,Zheng J,Cai J,Zeng K,Zhou C,Zhang J,Li S,Li H,Chen L,He L,Chen H,Fu H,Zhang Q,Chen G,Yang Y,Zhang Y.Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response.FASEB J 2019;33:1695-1710[PMID:30226809 DOI:10.1096/fj.201800131RR]
75 Tofi?o-Vian M,Guillén MI,Pérez Del Caz MD,Castejón MA,Alcaraz MJ.Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts.Oxid Med Cell Longev 2017;2017:7197598[PMID:29230269 DOI:10.1155/2017/7197598]
76 Xu M,Bradley EW,Weivoda MM,Hwang SM,Pirtskhalava T,Decklever T,Curran GL,Ogrodnik M,Jurk D,Johnson KO,Lowe V,Tchkonia T,Westendorf JJ,Kirkland JL.Transplanted Senescent Cells Induce an Osteoarthritis-Like Condition in Mice.J Gerontol A Biol Sci Med Sci 2017;72:780-785[PMID:27516624 DOI:10.1093/gerona/glw154]
77 McCulloch K,Litherland GJ,Rai TS.Cellular senescence in osteoarthritis pathology.Aging Cell 2017;16:210-218[PMID:28124466 DOI:10.1111/acel.12562]
78 Platas J,Guillén MI,Pérez Del Caz MD,Gomar F,Castejón MA,Mirabet V,Alcaraz MJ.Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes.Aging(Albany NY)2016;8:1703-1717[PMID:27490266 DOI:10.18632/aging.101007]
79 Bebelman MP,Smit MJ,Pegtel DM,Baglio SR.Biogenesis and function of extracellular vesicles in cancer.Pharmacol Ther 2018;188:1-11[PMID:29476772 DOI:10.1016/j.pharmthera.2018.02.013]
80 Phinney DG,Pittenger MF.Concise Review:MSC-Derived Exosomes for Cell-Free Therapy.Stem Cells2017;35:851-858[PMID:28294454 DOI:10.1002/stem.2575]
81 Lin S,Zhu B,Huang G,Zeng Q,Wang C.Microvesicles derived from human bone marrow mesenchymal stem cells promote U2OS cell growth under hypoxia:the role of PI3K/AKT and HIF-1α.Hum Cell 2019;32:64-74[PMID:30506278 DOI:10.1007/s13577-018-0224-z]
82 Zhu Z,Zhang Y,Zhang Y,Zhang H,Liu W,Zhang N,Zhang X,Zhou G,Wu L,Hua K,Ding J.Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAs in vitro.Hum Reprod 2019;34:248-260[PMID:30576496 DOI:10.1093/humrep/dey344]
83 Kulkarni R,Bajaj M,Ghode S,Jalnapurkar S,Limaye L,Kale VP.Intercellular Transfer of Microvesicles from Young Mesenchymal Stromal Cells Rejuvenates Aged Murine Hematopoietic Stem Cells.Stem Cells2018;36:420-433[PMID:29230885 DOI:10.1002/stem.2756]
84 Khayrullin A,Krishnan P,Martinez-Nater L,Mendhe B,Fulzele S,Liu Y,Mattison JA,Hamrick MW.Very Long-Chain C24:1 Ceramide Is Increased in Serum Extracellular Vesicles with Aging and Can Induce Senescence in Bone-Derived Mesenchymal Stem Cells.Cells 2019;8:pii:E37[PMID:30634626DOI:10.3390/cells8010037]