High-serum preconditioning promotes serum-induced recovery and partially restores the regenerative competence of older DPSCs through reconfiguration of functional and molecular programs without full reversion to a youthful state.
Key Findings
Results
High-serum preconditioning significantly enhanced proliferation and colony-forming efficiency in older dental pulp stem cells (DPSCs).
Comparisons were made between young, older, and high-serum-conditioned DPSCs from both rat and human sources.
In vitro assays assessed proliferation, survival, and colony-forming efficiency.
High-serum preconditioning approached the proliferative levels observed in young DPSCs.
Human DPSCs cultured under high-serum conditions similarly exhibited increased proliferation and viability.
Results
High-serum preconditioning restored osteogenesis and neurogenesis in older DPSCs, approaching the differentiation levels of young cells.
Multilineage differentiation capacity was assessed using in vitro differentiation assays.
Both osteogenic and neurogenic differentiation were restored through serum-induced recovery.
Human DPSCs also exhibited increased lineage-specific differentiation capacity under high-serum conditions.
Stable expression of mesenchymal stem cell markers was maintained in human DPSCs under high-serum conditions.
Results
Transplantation of high-serum-conditioned DPSCs resulted in organized axonal regeneration with compact myelin formation in vivo.
In vivo functional regeneration models were used to assess transplanted high-serum-conditioned DPSCs.
Axonal regeneration was described as 'organized' and accompanied by 'compact myelin formation.'
In vivo outcomes demonstrated 'functional recovery beyond in vitro outcomes.'
Both neural and bone regeneration were assessed in separate in vivo models.
Results
High-serum-conditioned DPSCs showed improved bone regeneration in calvarial defect models in vivo.
A calvarial defect model was used to assess in vivo bone regeneration.
High-serum-conditioned DPSCs demonstrated improved bone regeneration compared to untreated older DPSCs.
Functional recovery was observed beyond what was measured in in vitro outcomes.
Results
Transcriptomic analysis revealed extensive gene expression remodeling under high-serum conditions, including activation of stemness- and cell cycle-related gene programs and suppression of senescence-associated transcripts.
Transcriptomic profiling was conducted on human DPSCs.
High-serum conditions activated 'stemness- and cell cycle-related gene programs.'
Senescence-associated transcripts were suppressed under high-serum conditions.
Global gene expression patterns indicated 'only partial convergence toward a youthful transcriptional state rather than complete rejuvenation.'
Discussion
High-serum preconditioning achieved only partial, not complete, transcriptional rejuvenation of older DPSCs.
Global gene expression patterns were compared between young, older, and high-serum-conditioned DPSCs.
The study found 'only partial convergence toward a youthful transcriptional state rather than complete rejuvenation.'
The authors describe this as 'reconfiguration of functional and molecular programs without full reversion to a youthful state.'
The study characterizes its findings as 'preliminary insight into serum-induced recovery.'
Background
Aging impairs the proliferative, survival, and differentiation capacities of DPSCs, limiting their regenerative potential.
Both rat and human DPSCs were used to systematically investigate age-associated functional decline.
Age-associated decline was documented across proliferation, survival, colony-forming efficiency, and multilineage differentiation.
This age-related impairment provided the basis for investigating high-serum preconditioning as a recovery strategy.
What This Means
This research suggests that dental pulp stem cells (DPSCs) — stem cells found in the pulp of teeth — lose their ability to grow, survive, and develop into specialized cell types as they age, which limits their usefulness for tissue repair and regeneration. The study tested whether exposing these aged cells to a high concentration of serum (the liquid component of blood, which contains many growth factors and signaling molecules) before using them could partially reverse this age-related decline. The researchers compared young, older, and 'high-serum preconditioned' DPSCs from both rats and humans using lab tests and animal models.
This research suggests that high-serum preconditioning meaningfully improved the ability of older DPSCs to multiply, form colonies, and differentiate into bone and nerve cells in the laboratory. When transplanted into animals, these treated cells also produced organized nerve fiber regrowth with healthy myelin (the protective coating around nerves) and improved bone healing in skull defect models. Analysis of gene activity in human DPSCs showed that the high-serum treatment switched on genes related to stem cell identity and cell division while switching off genes associated with cellular aging, though the overall gene activity pattern only partially resembled that of young cells rather than fully reverting to a youthful state.
This research suggests that exposing aged dental pulp stem cells to high-serum conditions before transplantation could be a strategy to improve their regenerative performance, potentially making older donor cells more viable for future cell-based therapies for nerve or bone repair. However, because the rejuvenation was only partial and the study is described as preliminary, further work is needed to identify which specific factors in serum are responsible for the observed recovery and to determine whether these findings translate to clinical applications.
Park C, Moon J, Lee S, Lee E, Park J, Kim S. (2026). Serum-induced recovery of proliferative capacity and differentiation potential in aged dental pulp stem cells.. Stem cells translational medicine. https://doi.org/10.1093/stcltm/szag072