Abstract

Human bone marrow mesenchymal stem cells (HBMSCs) has been the gold standard for bone regeneration. However, the low proliferation rate and long doubling time limited its clinical applications. This study aims to compare the bone tissue engineering efficacy of human dental pulp stem cells (HDPSCs) with HBMSCs in 2D, and 3D anorganic bone mineral (ABM) coated with a biomimetic collagen peptide (ABM-P-15) for improving bone-forming speed and efficacy in vitro and in vivo. The multipotential of both HDPSCs and HBMSCs have been compared in vitro. The bone formation of HDPSCs on ABM-P-15 was tested using in vivo model. The osteogenic potential of the cells was confirmed by alkaline phosphatase (ALP) and immunohistological staining for osteogenic markers. Enhanced ALP, collagen, lipid droplet, or glycosaminoglycans production were visible in HDPSCs and HBMSCs after osteogenic, adipogenic and chondrogenic induction. HDPSC showed stronger ALP staining compared to HBMSCs. Confocal images showed more viable HDPSCs on both ABM-P-15 and ABM scaffolds compared to HBMSCs on similar scaffolds. ABM-P-15 enhanced cell attachment/spreading/bridging formation on ABM-P-15 scaffolds and significantly increased quantitative ALP specific activities of the HDPSCs and HBMSCs. After 8 weeks in vivo implantation in diffusion chamber model, the HDPSCs on ABM-P-15 scaffolds showed extensive high organised collagenous matrix formation that was positive for COL-I and OCN compared to ABM alone. In conclusion, the HDPSCs have a higher proliferation rate and better osteogenic capacity, which indicated the potential of combining HDPSCs with ABM-P-15 scaffolds for improving bone regeneration speed and efficacy.

Highlights

  • The increasing clinical demand for bone regeneration and repair in the context of our ageing population poses a challenge both to healthcare providers and society (Iaquinta et al 2019)

  • The human dental pulp stem cells (HDPSCs) have a higher proliferation rate and better osteogenic capacity, which indicated the potential of combining HDPSCs with anorganic bone mineral (ABM)-P-15 scaffolds for improving bone regeneration speed and efficacy

  • Multi-lineage differentiation capacity of HDPSCs compared to Human bone marrow mesenchymal stem cells (HBMSCs) in monolayer culture

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Summary

Introduction

The increasing clinical demand for bone regeneration and repair in the context of our ageing population poses a challenge both to healthcare providers and society (Iaquinta et al 2019). It has been documented that the poor response of these cells is due to the loss of potential to proliferate and differentiate with increasing donor age (Jones and Schafer 2015; Kern et al 2006; Muschler et al 2001; Yamada et al 2010; Yoshii et al 2009) Taken together, these factors have led to the search for an alternative adult stem cell sources which can be accessed with minimal invasion and provide the stem cells with similar or better regenerative potential as HBMSCs. In nature, every individual, during their lifetime, experiences teeth loss (80% of subjects had lost one or more tooth, and the mean tooth loss was 5.09)(Ribeiro et al 2015), which provides an opportunity to access dental tissues with minimal invasion making the option of isolating of stem cells from dental pulp a promising alternative source to HBMSCs. Pulp tissues can be obtained from either permanent or deciduous teeth, wisdom teeth (third molars) have long been a preferred choice of the permanent teeth (Ledesma-Martinez et al 2016). Extensive research has since been carried out pursuant to a good understanding of HDPSCs and their potential in tissue engineering (Kawashima and Okiji 2016)

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