Variation in human dental pulp stem cell ageing profiles reflect contrasting proliferative and regenerative capabilities.
Dental pulp stem cells (DPSCs) are increasingly being recognized as a viable cell source for regenerative medicine. Although significant variations in their ex vivo expansion are well-established, DPSC proliferative heterogeneity remains poorly understood, despite such characteristics influencing their regenerative and therapeutic potential. This study assessed clonal human DPSC regenerative potential and the impact of cellular senescence on these responses, to better understand DPSC functional behaviour.



All DPSCs were negative for hTERT. Whilst one DPSC population reached >80 PDs before senescence, other populations only achieved <40 PDs, correlating with DPSCs with high proliferative capacities possessing longer telomeres (18.9 kb) than less proliferative populations (5-13 kb). High proliferative capacity DPSCs exhibited prolonged stem cell marker expression, but lacked CD271. Early-onset senescence, stem cell marker loss and positive CD271 expression in DPSCs with low proliferative capacities were associated with impaired osteogenic and chondrogenic differentiation, favouring adipogenesis. DPSCs with high proliferative capacities only demonstrated impaired differentiation following prolonged expansion (>60 PDs).



This study has identified that proliferative and regenerative heterogeneity is related to contrasting telomere lengths and CD271 expression between DPSC populations. These characteristics may ultimately be used to selectively screen and isolate high proliferative capacity/multi-potent DPSCs for regenerative medicine exploitation.
Mineralised Tissue Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, CF14 4XY, Cardiff, UK.|Cardiff Institute Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, CF14 4XY, UK.
Amr
A
Alraies
Cardiff Institute Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, CF14 4XY, UK.|Stem Cells, Wound Repair and Regeneration, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK.
Nadia Y A
NY
Alaidaroos
Mineralised Tissue Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, CF14 4XY, Cardiff, UK.|Cardiff Institute Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, CF14 4XY, UK.
Rachel J
RJ
Waddington
Cardiff Institute Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, CF14 4XY, UK.|Stem Cells, Wound Repair and Regeneration, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK.
Ryan
R
Moseley
Mineralised Tissue Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, CF14 4XY, Cardiff, UK. Sloanaj@cardiff.ac.uk.|Cardiff Institute Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, CF14 4XY, UK. Sloanaj@cardiff.ac.uk.
Alastair J
AJ
Sloan
D050156:Adipogenesis; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D016922:Cellular Senescence; D020219:Chondrogenesis; D003782:Dental Pulp / Q000166:cytology*; D005260:Female; D006801:Humans; D010012:Osteogenesis; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D055815:Young Adult
D015415:Biomarkers
CD271; Cellular senescence; Cumulative population doublings; Dental pulp; Differentiation; Multi-potency; Stem cells; Telomeres