Periodontal ligament (PDL) stem cell properties are critical in the periodontal tissue regeneration for periodontitis. Previously, we have demonstrated that cigarette smoking attenuates PDL-derived stem cell (PDLSC) regenerative properties. Here, we report the findings on the regenerative properties of human PDLSCs with different donor ages and the underlying mechanisms. Human PDLSCs from 18 independent donors were divided into different age groups (≤ 20, 20–40, and > 40 years old). The proliferation of PDLSCs with donor age of ≤ 20 years old was significantly higher than that of the 20–40- and > 40-years-old groups, whereas the migration of PDLSCs with donor age of ≤ 20 and 20–40 years old was significantly higher than that of the > 40-years-old group. Moreover, the mesodermal lineage differentiation capabilities of PDLSCs were also higher in the donor age group of ≤ 20 years old than the donor age of > 40 years old. In addition, shorter telomere length and lower expression of SSEA4 were found in PDLSCs with donor age of > 40 years old, compared with those with donor age of ≤ 20-years-old group. Besides, PDLSCs with donor age of 20–40 and > 40 years old had higher IL6 and CXCL8 gene expressions. In summary, results from this study revealed the attenuated proliferation, migration, and mesodermal lineage differentiation properties in human PDLSCs with older donor ages. Donor age of PDLSCs should be considered as the selection criteria for the periodontal tissue regeneration treatment.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
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 36:844–855
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 12:881–887
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 32:83–91
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
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 18:968–973
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–C372
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 54:3965–3974
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
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 9:38–44
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–e51
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 79:74–83
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 30:352–361
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 20:25–34
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–e23
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 19:277–285
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217
Lossdörfer S, Kraus D, Jäger A (2010) Aging affects the phenotypic characteristics of human periodontal ligament cells and the cellular response to hormonal stimulation in vitro. J Periodontal Res 45:764–771
McHugh D, Gil J (2018) Senescence and aging: causes, consequences, and therapeutic avenues. J Cell Biol 217:65–77
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 22:781–790
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
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
O’Hagan-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’ homeostasis. Oncotarget 7:13285–13296
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 10:259–272
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 367:229–241
Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366:1809–1820
Trivanović D, Jauković A, Popović B, Krstić J, Mojsilović S, Okić-Djordjević I, Kukolj T, Obradović 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 141:61–73
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 18:344–354
Wu Y, Chen L, Scott PG, Tredget EE (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25:2648–2659
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 22:70–82
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 8:392–403
Yang YK (2018) Aging of mesenchymal stem cells: implication in regenerative medicine. Regen Ther 9:120–122
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 33:6974–6986
Zhang XY, Ng TK, Brelén 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
Zhang XY, Ng TK, Brelén 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
This work was supported in part by the Special Fund for the Innovative Science and Technology Strategy of Guangdong Province (project code 180918154960752 to T.K.N.), an internal grant from the Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong (18-001 to T.K.N.), and the Natural Science Foundation of Guangdong Province (project code 2016A030313063 to Y.H.), China.
Conflict of interest
The authors declare that they have no conflicts of interest.
Written informed consents were obtained from all donors or their legally authorized representatives.
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
About this article
Cite this article
Ng, T.K., Chen, C., Xu, C. et al. Attenuated regenerative properties in human periodontal ligament–derived stem cells of older donor ages with shorter telomere length and lower SSEA4 expression. Cell Tissue Res (2020). https://doi.org/10.1007/s00441-020-03176-y
- Human periodontal ligament–derived stem cells
- Age effect
- Regenerative properties