Evaluating the efficacy of human dental pulp stem cells and scaffold combination for bone regeneration in animal models: a systematic review and meta-analysis

Abstract

Introduction Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility, high proliferation rate, self-renewal and osteogenic differentiation capacity. Various organic and inorganic scaffold materials were pre-seeded with human dental pulp stem cells in animals, with promising outcomes in new bone formation. Nevertheless, the clinical trial for bone regeneration using dental pulp stem cells is still in its infancy. Thus, the aim of this systematic review and meta-analysis is to synthesise the evidence of the efficacy of human dental pulp stem cells and the scaffold combination for bone regeneration in animal bone defect models. Methodology This study was registered in PROSPERO (CRD2021274976), and PRISMA guideline was followed to include the relevant full-text papers using exclusion and inclusion criteria. Data were extracted for the systematic review. Quality assessment and the risk of bias were also carried out using the CAMARADES tool. Quantitative bone regeneration data of the experimental (scaffold + hDPSC/SHED) and the control (scaffold-only) groups were also extracted for meta-analysis. Results Forty-nine papers were included for systematic review and only 27 of them were qualified for meta-analysis. 90% of the included papers were assessed as medium to low risk. In the meta-analysis, qualified studies were grouped by the unit of bone regeneration measurement. Overall, bone regeneration was significantly higher (p < 0.0001) in experimental group (scaffold + hDPSC/SHED) compared to the control group (scaffold-only) (SMD: 1.863, 95% CI 1.121–2.605). However, the effect is almost entirely driven by the % new bone formation group (SMD: 3.929, 95% CI 2.612–5.246) while % BV/TV (SMD: 2.693, 95% CI − 0.001–5.388) shows a marginal effect. Dogs and hydroxyapatite-containing scaffolds have the highest capacity in % new bone formation in response to human DPSC/SHED. The funnel plot exhibits no apparent asymmetry representing a lack of remarkable publication bias. Sensitivity analysis also indicated that the results generated in this meta-analysis are robust and reliable. Conclusion This is the first synthesised evidence showing that human DPSCs/SHED and scaffold combination enhanced bone regeneration highly significantly compared to the cell-free scaffold irrespective of scaffold type and animal species used. So, dental pulp stem cells could be a promising tool for treating various bone diseases, and more clinical trials need to be conducted to evaluate the effectiveness of dental pulp stem cell-based therapies.

Editorial: Tissue regeneration using dental stem cells

“…Dental MSCs (DMSCs) have been found in various dental tissues; moreover, DMSCs have gained growing interest from the scientific community because of their easy accessibility, and thanks to their high strategic plasticity both in dental tissues repair and in regenerating several types of human tissues, including bone, cartilage, muscle, and neural tissue. Despite oral tissues not being the most used niches of MSCs, we should carefully rethink the role of DMSCs in tissue regeneration, as their use may lead to a significant advance of knowledge in regenerative dentistry, impacting on the future treatments of various systemic diseases (Namjoynik et al, 2023;Tatullo et al, 2023).This Research Topic has investigated a wide range of Research Topic, confirming the valuable potentialities of DMSCs in tissue regeneration. Several approaches have been proposed to optimize and enhance the regenerative potential of MSC, such as the use of media conditioned with different growth factors, or cytokines and bioactive molecules (Liu et al, 2022;Ueda et al, 2022).…”

“…Dental MSCs (DMSCs) have been found in various dental tissues; moreover, DMSCs have gained growing interest from the scientific community because of their easy accessibility, and thanks to their high strategic plasticity both in dental tissues repair and in regenerating several types of human tissues, including bone, cartilage, muscle, and neural tissue. Despite oral tissues not being the most used niches of MSCs, we should carefully rethink the role of DMSCs in tissue regeneration, as their use may lead to a significant advance of knowledge in regenerative dentistry, impacting on the future treatments of various systemic diseases (Namjoynik et al, 2023;Tatullo et al, 2023).…”

Isolation, identification and osteogenic capability analysis of mesenchymal stem cells derived from different layers of human maxillary sinus membrane

“…In animal and pre‐clinical studies, PDLMSCs (Bright et al, 2015; Tassi et al, 2017) and DPSCs (Leyendecker Junior et al, 2018; Namjoynik et al, 2023) have been extensively investigated. The two cell types were also found to show comparable osteogenic capability as BMSCs (Kadkhoda et al, 2024; Li et al, 2020).…”

Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway

“…Previous studies have shown that hDPSCs for BTE are abundant, easily accessible, can be harvested with minimal invasiveness, and grow efficiently in culture [ 42 , 43 ]. Accumulating evidence indicates that the microenvironment influences the fate of hDPSCs by regulating signalling pathways and genes associated with differentiation [ 18 , 43 ]. The development of functional hydrogel scaffolds that mimic ECM is a promising strategy for BTE.…”