Abstract

Adipose tissue-derived stem cells (ADSCs) and dental pulp stem cells (DPSCs) have become promising sources for bone tissue engineering. Our study aimed at evaluating bone regeneration potential of cryopreserved ADSCs and DPSCs combined with bovine-derived xenografts with 10% porcine collagen. In vitro studies revealed that although DPSCs had higher proliferative abilities, ADSCs exhibited greater mineral depositions and higher osteogenic-related gene expression, indicating better osteogenic differentiation potential of ADSCs. After applying cryopreserved ADSCs and DPSCs in a critical-sized calvarial defect model, both cryopreserved mesenchymal stem cells significantly improved bone volume density and new bone area at 2, 4, and 8 weeks. Furthermore, the combined treatment with ADSCs and xenografts was more efficient in enhancing bone repair processes compared to combined treatment with DPCSs at all-time points. We also evaluated the sequential early bone healing process both histologically and radiographically, confirming a high agreement between these two methods. Based on these results, we propose grafting of the tissue-engineered construct seeded with cryopreserved ADSCs as a useful strategy in accelerating bone healing processes.

Highlights

  • Bone defects caused by trauma, necrosis and tumors have long been recognized as a serious clinical problem due a high incidence of impaired healing (Rao and Stegemann, 2013)

  • Flow cytometry analysis showed that both adipose tissue-derived stem cells (ADSCs) and dental pulp stem cells (DPSCs) expressed mesenchymal stem cells (MSCs)-associated surface markers, such as CD73, CD90, and CD105, but not CD34, CD45 and HLA-DR, confirming the immune-phenotype and the stemness itself of these isolated cells (Supplementary Figure 1)

  • We focused on the osteogenic differentiation of ADSCs and DPSCs

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Summary

Introduction

Bone defects caused by trauma, necrosis and tumors have long been recognized as a serious clinical problem due a high incidence of impaired healing (Rao and Stegemann, 2013). Mesenchymal stem cells (MSCs)-based therapy has emerged as an effective bone construction technique due to multi-differentiation potential of these cells (Nancarrow-Lei et al, 2017). Adipose tissue-derived stem cells (ADSCs) and dental pulp stem cells (DPSCs) have emerged as promising alternatives to BMSCs, as they can provide a relative abundance of MSCs (Caetano et al, 2019). Cryopreservation of MSCs would provide several benefits such as long-term storage, adjusting therapeutic cell doses and reducing contamination for safe clinical practices (Ma et al, 2012). Few studies have investigated the osteogenic capacities of cryopreserved DPSCs and ADSCs in bone healing processes

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