Abstract

Adipose tissue is composed mostly of adipocytes that are in contact with capillaries. By using a ceiling culture method based on buoyancy, lipid-free fibroblast-like cells, also known as dedifferentiated fat (DFAT) cells, can be separated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and transdifferentiate into various cell types under appropriate culture conditions. Herein, we sought to compare the regenerative potential of collagen matrix alone (control) with autologous DFAT cell-loaded collagen matrix transplantation in adult miniature pigs (microminipigs; MMPs). We established and transplanted DFAT cells into inflammation-inducing periodontal class II furcation defects. At 12 weeks after cell transplantation, a marked attachment gain was observed based on the clinical parameters of probing depth (PD) and clinical attachment level (CAL). Additionally, micro computed tomography (CT) revealed hard tissue formation in furcation defects of the second premolar. The cemento-enamel junction and alveolar bone crest distance was significantly shorter following transplantation. Moreover, newly formed cellular cementum, well-oriented periodontal ligament-like fibers, and alveolar bone formation were observed via histological analysis. No teratomas were found in the internal organs of recipient MMPs. Taken together, these findings suggest that DFAT cells can safely enhance periodontal tissue regeneration.

Highlights

  • Periodontitis is a bacteria-induced chronic inflammatory condition, which leads to the destruction tooth-supporting structures and subsequent tooth loss [1,2]

  • Various studies have demonstrated that mesenchymal stem cells (MSCs) possessing sustained self-renewal and multi-lineage differentiation capability derived from the periodontal ligament, bone marrow, and alveolar periosteal can be effective for periodontal tissue regeneration in large animal models [7,8,9,10,11]

  • Inflammation-inducing periodontal class II furcation defects were successfully induced in the second premolars of the bilateral mandible at 0 weeks

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Summary

Introduction

Periodontitis is a bacteria-induced chronic inflammatory condition, which leads to the destruction tooth-supporting structures and subsequent tooth loss [1,2]. Periodontal regeneration is a demanding procedure that requires restoration of the structure and function of the periodontal ligament, cementum, and alveolar bone. Appropriate cells, signaling factors, scaffolds, blood supply, mechanical loading, and microbial control are essential for creating optimal conditions for successful periodontal tissue reconstruction [4,5]. Various studies have demonstrated that mesenchymal stem cells (MSCs) possessing sustained self-renewal and multi-lineage differentiation capability derived from the periodontal ligament, bone marrow, and alveolar periosteal can be effective for periodontal tissue regeneration in large animal models [7,8,9,10,11]

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