{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T18:42:54Z","timestamp":1763664174584,"version":"3.37.3"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Special Fund for the Innovative Science and Technology Strategy of Guangdong Province","award":["180918154960752"],"award-info":[{"award-number":["180918154960752"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2016A030313063"],"award-info":[{"award-number":["2016A030313063"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Internal grant from the Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong","award":["18-001"],"award-info":[{"award-number":["18-001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Tissue Res"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1007\/s00441-020-03176-y","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T06:03:55Z","timestamp":1581401035000},"page":"71-81","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Attenuated regenerative properties in human periodontal ligament\u2013derived stem cells of older donor ages with shorter telomere length and lower SSEA4 expression"],"prefix":"10.1007","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-7229","authenticated-orcid":false,"given":"Tsz Kin","family":"Ng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong-Bo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanxuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Jian","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herman S.","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi Pui","family":"Pang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqiang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"3176_CR1","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1002\/stem.2812","volume":"36","author":"LP Cen","year":"2018","unstructured":"Cen LP, Ng TK, Liang JJ, Zhuang X, Yao X, Yam GH, Chen H, Cheung HS, Zhang M, Pang CP (2018) Human periodontal ligament-derived stem cells promote retinal ganglion cell survival and axon regeneration after optic nerve injury. Stem Cells 36:844\u2013855","journal-title":"Stem Cells"},{"key":"3176_CR2","doi-asserted-by":"publisher","first-page":"881","DOI":"10.3109\/14653249.2010.501790","volume":"12","author":"DM Choumerianou","year":"2010","unstructured":"Choumerianou DM, Martimianaki G, Stiakaki E, Kalmanti L, Kalmanti M, Dimitriou H (2010) Comparative study of stemness characteristics of mesenchymal cells from bone marrow of children and adults. Cytotherapy 12:881\u2013887","journal-title":"Cytotherapy"},{"key":"3176_CR3","doi-asserted-by":"publisher","first-page":"83","DOI":"10.24920\/J1001-9294.2017.012","volume":"32","author":"T Du","year":"2017","unstructured":"Du T, Liu N, Gu B, Li L, Yuan Y, Zhang W, Zhang T (2017) Effects of aging on the proliferation and differentiation capacity of human periodontal ligament stem cells. Chin Med Sci J 32:83\u201391","journal-title":"Chin Med Sci J"},{"key":"3176_CR4","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.327","volume":"7","author":"F Gao","year":"2016","unstructured":"Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, Tse HF, Fu QL, Lian Q (2016) Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis 7:e2062","journal-title":"Cell Death Dis"},{"key":"3176_CR5","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1089\/ten.tea.2011.0545","volume":"18","author":"E Gibon","year":"2012","unstructured":"Gibon E, Batke B, Jawad MU, Fritton K, Rao A, Yao Z, Biswal S, Gambhir SS, Goodman SB (2012) MC3T3-E1 osteoprogenitor cells systemically migrate to a bone defect and enhance bone healing. Tissue Eng. Part A 18:968\u2013973","journal-title":"Tissue Eng. Part A"},{"key":"3176_CR6","doi-asserted-by":"publisher","first-page":"C362","DOI":"10.1152\/ajpcell.00013.2010","volume":"301","author":"X Hu","year":"2011","unstructured":"Hu X, Wei L, Taylor TM, Wei J, Zhou X, Wang JA, Yu SP (2011) Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol 301:C362\u2013C372","journal-title":"Am J Physiol Cell Physiol"},{"key":"3176_CR7","doi-asserted-by":"publisher","first-page":"3965","DOI":"10.1167\/iovs.13-11910","volume":"54","author":"L Huang","year":"2013","unstructured":"Huang L, Liang J, Geng Y, Tsang WM, Yao X, Jhanji V, Zhang M, Cheung HS, Pang CP, Yam GH (2013) Directing adult human periodontal ligament-derived stem cells to retinal fate. Invest Ophthalmol Vis Sci 54:3965\u20133974","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"3176_CR8","first-page":"9201374","volume":"2018","author":"Y Huang","year":"2018","unstructured":"Huang Y, Ng TK, Chen CB, Huang B, Liang J, Pang CP, Zhang M (2018) Notch signaling activation enhances human adipose-derived stem cell retinal differentiation. Stem Cells Int 2018:9201374","journal-title":"Stem Cells Int"},{"key":"3176_CR9","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.reth.2018.07.002","volume":"9","author":"T Iwata","year":"2018","unstructured":"Iwata T, Yamato M, Washio K, Yoshida T, Tsumanuma Y, Yamada A, Onizuka S, Izumi Y, Ando T, Okano T, Ishikawa I (2018) Periodontal regeneration with autologous periodontal ligament-derived cell sheets - a safety and efficacy study in ten patients. Regen Ther 9:38\u201344","journal-title":"Regen Ther"},{"key":"3176_CR10","doi-asserted-by":"publisher","first-page":"e44","DOI":"10.1902\/jop.2015.150474","volume":"87","author":"H Kato","year":"2016","unstructured":"Kato H, Taguchi Y, Tominaga K, Kimura D, Yamawaki I, Noguchi M, Yamauchi N, Tamura I, Tanaka A, Umeda M (2016) High glucose concentrations suppress the proliferation of human periodontal ligament stem cells and their differentiation into osteoblasts. J Periodontol 87:e44\u2013e51","journal-title":"J Periodontol"},{"key":"3176_CR11","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.diff.2009.10.005","volume":"79","author":"N Kawanabe","year":"2010","unstructured":"Kawanabe N, Murata S, Murakami K, Ishihara Y, Hayano S, Kurosaka H, Kamioka H, Takano-Yamamoto T, Yamashiro T (2010) Isolation of multipotent stem cells in human periodontal ligament using stage-specific embryonic antigen-4. Differentiation 79:74\u201383","journal-title":"Differentiation"},{"key":"3176_CR12","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.arthro.2013.12.009","volume":"30","author":"J Li","year":"2014","unstructured":"Li J, Campbell DD, Bal GK, Pei M (2014a) Can arthroscopically harvested synovial stem cells be preferentially sorted using stage-specific embryonic antigen 4 antibody for cartilage, bone, and adipose regeneration? Arthroscopy 30:352\u2013361","journal-title":"Arthroscopy"},{"key":"3176_CR13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/odi.12086","volume":"20","author":"Z Li","year":"2014","unstructured":"Li Z, Jiang CM, An S, Cheng Q, Huang YF, Wang YT, Gou YC, Xiao L, Yu WJ, Wang J (2014b) Immunomodulatory properties of dental tissue-derived mesenchymal stem cells. Oral Dis 20:25\u201334","journal-title":"Oral Dis"},{"key":"3176_CR14","doi-asserted-by":"publisher","first-page":"e12","DOI":"10.1902\/jop.2016.160338","volume":"88","author":"Q Li","year":"2017","unstructured":"Li Q, Ma Y, Zhu Y, Zhang T, Zhou Y (2017) Declined expression of histone deacetylase 6 contributes to periodontal ligament stem cell aging. J Periodontol 88:e12\u2013e23","journal-title":"J Periodontol"},{"key":"3176_CR15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/s10561-017-9672-z","volume":"19","author":"X Li","year":"2018","unstructured":"Li X, Li J, Zhao X, Wang Q, Yang X, Cheng Y, Zhou M, Wang G, Dang E, Yang X, Hou R, An P, Yin G, Zhang K (2018) Comparative analysis of molecular activity in dermal mesenchymal stem cells from different passages. Cell Tissue Bank 19:277\u2013285","journal-title":"Cell Tissue Bank"},{"key":"3176_CR16","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C L\u00f3pez-Ot\u00edn","year":"2013","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194\u20131217","journal-title":"Cell"},{"key":"3176_CR17","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1111\/j.1600-0765.2010.01297.x","volume":"45","author":"S Lossd\u00f6rfer","year":"2010","unstructured":"Lossd\u00f6rfer S, Kraus D, J\u00e4ger A (2010) Aging affects the phenotypic characteristics of human periodontal ligament cells and the cellular response to hormonal stimulation in vitro. J Periodontal Res 45:764\u2013771","journal-title":"J Periodontal Res"},{"key":"3176_CR18","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1083\/jcb.201708092","volume":"217","author":"D McHugh","year":"2018","unstructured":"McHugh D, Gil J (2018) Senescence and aging: causes, consequences, and therapeutic avenues. J Cell Biol 217:65\u201377","journal-title":"J Cell Biol"},{"key":"3176_CR19","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1089\/scd.2012.0434","volume":"22","author":"TK Ng","year":"2013","unstructured":"Ng TK, Carballosa CM, Pelaez D, Wong HK, Choy KW, Pang CP, Cheung HS (2013) Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential. Stem Cells Dev 22:781\u2013790","journal-title":"Stem Cells Dev"},{"key":"3176_CR20","doi-asserted-by":"publisher","first-page":"7828","DOI":"10.1038\/srep07828","volume":"5","author":"TK Ng","year":"2015","unstructured":"Ng TK, Huang L, Cao D, Yip YW, Tsang WM, Yam GH, Pang CP, Cheung HS (2015a) Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials. Sci Rep 5:7828","journal-title":"Sci Rep"},{"key":"3176_CR21","doi-asserted-by":"publisher","first-page":"16429","DOI":"10.1038\/srep16429","volume":"5","author":"TK Ng","year":"2015","unstructured":"Ng TK, Yung JS, Choy KW, Cao D, Leung CK, Cheung HS, Pang CP (2015b) Transdifferentiation of periodontal ligament-derived stem cells into retinal ganglion-like cells and its microRNA signature. Sci Rep 5:16429","journal-title":"Sci Rep"},{"key":"3176_CR22","doi-asserted-by":"publisher","first-page":"13285","DOI":"10.18632\/oncotarget.7690","volume":"7","author":"K O\u2019Hagan-Wong","year":"2016","unstructured":"O\u2019Hagan-Wong K, Nadeau S, Carrier-Leclerc A, Apablaza F, Hamdy R, Shum-Tim D, Rodier F, Colmegna I (2016) Increased IL-6 secretion by aged human mesenchymal stromal cells disrupts hematopoietic stem and progenitor cells\u2019 homeostasis. Oncotarget 7:13285\u201313296","journal-title":"Oncotarget"},{"key":"3176_CR23","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.stem.2012.02.003","volume":"10","author":"D Park","year":"2012","unstructured":"Park D, Spencer JA, Koh BI, Kobayashi T, Fujisaki J, Clemens TL, Lin CP, Kronenberg HM, Scadden DT (2012) Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell 10:259\u2013272","journal-title":"Cell Stem Cell"},{"key":"3176_CR24","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00441-016-2503-x","volume":"367","author":"D Pelaez","year":"2017","unstructured":"Pelaez D, Acosta Torres Z, Ng TK, Choy KW, Pang CP, Cheung HS (2017) Cardiomyogenesis of periodontal ligament-derived stem cells by dynamic tensile strain. Cell Tissue Res 367:229\u2013241","journal-title":"Cell Tissue Res"},{"key":"3176_CR25","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1016\/S0140-6736(05)67728-8","volume":"366","author":"BL Pihlstrom","year":"2005","unstructured":"Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809\u20131820","journal-title":"Lancet"},{"key":"3176_CR26","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.lfs.2015.09.019","volume":"141","author":"D Trivanovi\u0107","year":"2015","unstructured":"Trivanovi\u0107 D, Jaukovi\u0107 A, Popovi\u0107 B, Krsti\u0107 J, Mojsilovi\u0107 S, Oki\u0107-Djordjevi\u0107 I, Kukolj T, Obradovi\u0107 H, Santibanez JF, Bugarski D (2015) Mesenchymal stem cells of different origin: comparative evaluation of proliferative capacity, telomere length and pluripotency marker expression. Life Sci 141:61\u201373","journal-title":"Life Sci"},{"key":"3176_CR27","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1111\/jcmm.12192","volume":"18","author":"AB Vasandan","year":"2014","unstructured":"Vasandan AB, Shankar SR, Prasad P, Sowmya Jahnavi V, Bhonde RR, Jyothi Prasanna S (2014) Functional differences in mesenchymal stromal cells from human dental pulp and periodontal ligament. J Cell Mol Med 18:344\u2013354","journal-title":"J Cell Mol Med"},{"key":"3176_CR28","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1634\/stemcells.2007-0226","volume":"25","author":"Y Wu","year":"2007","unstructured":"Wu Y, Chen L, Scott PG, Tredget EE (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25:2648\u20132659","journal-title":"Stem Cells"},{"key":"3176_CR29","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.actbio.2015.04.024","volume":"22","author":"RX Wu","year":"2015","unstructured":"Wu RX, Bi CS, Yu Y, Zhang LL, Chen FM (2015) Age-related decline in the matrix contents and functional properties of human periodontal ligament stem cell sheets. Acta Biomater 22:70\u201382","journal-title":"Acta Biomater"},{"key":"3176_CR30","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1002\/sctm.18-0181","volume":"8","author":"XY Xu","year":"2019","unstructured":"Xu XY, Li X, Wang J, He XT, Sun HH, Chen FM (2019) Concise review: periodontal tissue regeneration using stem cells: strategies and translational considerations. Stem Cells Transl Med 8:392\u2013403","journal-title":"Stem Cells Transl Med"},{"key":"3176_CR31","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.reth.2018.09.002","volume":"9","author":"YK Yang","year":"2018","unstructured":"Yang YK (2018) Aging of mesenchymal stem cells: implication in regenerative medicine. Regen Ther 9:120\u2013122","journal-title":"Regen Ther"},{"key":"3176_CR32","doi-asserted-by":"publisher","first-page":"6974","DOI":"10.1016\/j.biomaterials.2012.06.032","volume":"33","author":"J Zhang","year":"2012","unstructured":"Zhang J, An Y, Gao LN, Zhang YJ, Jin Y, Chen FM (2012) The effect of aging on the pluripotential capacity and regenerative potential of human periodontal ligament stem cells. Biomaterials 33:6974\u20136986","journal-title":"Biomaterials"},{"key":"3176_CR33","doi-asserted-by":"publisher","first-page":"37279","DOI":"10.1038\/srep37279","volume":"6","author":"XY Zhang","year":"2016","unstructured":"Zhang XY, Ng TK, Brel\u00e9n ME, Wu D, Wang JX, Chan KP, Yung JSY, Cao D, Wang Y, Zhang S, Chan SO, Pang CP (2016) Continuous exposure to non-lethal doses of sodium iodate induces retinal pigment epithelial cell dysfunction. Sci Rep 6:37279","journal-title":"Sci Rep"},{"key":"3176_CR34","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1038\/s41598-017-03283-x","volume":"7","author":"XY Zhang","year":"2017","unstructured":"Zhang XY, Ng TK, Brel\u00e9n ME, Chan KP, Wu D, Yung JSY, Cao D, Wang Y, Zhang S, Chan SO, Pang CP (2017) Disruption of retinal pigment epithelial cell properties under the exposure of cotinine. Sci Rep 7:3139","journal-title":"Sci Rep"}],"container-title":["Cell and Tissue Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-020-03176-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00441-020-03176-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00441-020-03176-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T06:39:14Z","timestamp":1612939154000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00441-020-03176-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,11]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["3176"],"URL":"https:\/\/doi.org\/10.1007\/s00441-020-03176-y","relation":{},"ISSN":["0302-766X","1432-0878"],"issn-type":[{"type":"print","value":"0302-766X"},{"type":"electronic","value":"1432-0878"}],"subject":[],"published":{"date-parts":[[2020,2,11]]},"assertion":[{"value":"13 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Written informed consents were obtained from all donors or their legally authorized representatives.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"This study protocol was approved by the Human Ethics Committee of Shantou University Medical College (EC20100927(5)-P06), which is in accordance with the tenets of the Helsinki Declaration.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}