Use of Rat Mature Adipocyte-Derived Dedifferentiated Fat Cells as a Cell Source for Periodontal Tissue Regeneration.

Koichiro Kano,Keitaro Isokawa,Yoko Saito-Tamura,Katsuyuki Yamanaka,Niina Tsurumachi,Taku Toriumi,Yoshinori Arai,Daisuke Akita,Tadashi Kaneko,Momoko Sato-Shionome,Taro Matsumoto,Naoki Tsukimura,Tomohiko Ishigami,Takayuki Mashimo,Masaki Honda

doi:10.3389/fphys.2016.00050

Abstract

Lipid-free fibroblast-like cells, known as dedifferentiated fat (DFAT) cells, can be generated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and can transdifferentiate into various cell types under appropriate culture conditions. The first objective of this study was to compare the multilineage differentiation potential of DFAT cells with that of adipose-derived stem cells (ASCs) on mesenchymal stem cells. We obtained DFAT cells and ASCs from inbred rats and found that rat DFAT cells possess higher osteogenic differentiation potential than rat ASCs. On the other hand, DFAT cells show similar adipogenic differentiation, and chondrogenic differentiation potential in comparison with ASCs. The second objective of this study was to assess the regenerative potential of DFAT cells combined with novel solid scaffolds composed of PLGA (Poly d, l-lactic-co-glycolic acid) on periodontal tissue, and to compare this with the regenerative potential of ASCs combined with PLGA scaffolds. Cultured DFAT cells and ASCs were seeded onto PLGA scaffolds (DFAT/PLGA and ASCs/PLGA) and transplanted into periodontal fenestration defects in rat mandible. Micro computed tomography analysis revealed a significantly higher amount of bone regeneration in the DFAT/PLGA group compared with that of ASCs/PLGA and PLGA-alone groups at 2, 3, and 5 weeks after transplantation. Similarly, histomorphometric analysis showed that DFAT/PLGA groups had significantly greater width of cementum, periodontal ligament and alveolar bone than ASCs/PLGA and PLGA-alone groups. In addition, transplanted fluorescent-labeled DFAT cells were observed in the periodontal ligament beside the newly formed bone and cementum. These findings suggest that DFAT cells have a greater potential for enhancing periodontal tissue regeneration than ASCs. Therefore, DFAT cells are a promising cell source for periodontium regeneration.

Highlights

The use of adult mesenchymal stem cells (MSCs) seems to be ideal for practical periodontal regenerative medicine, because they are not subject to the restrictions such as embryonic stem cells (ESCs) or induced pluripotent stem cells (Prockop, 1997; Pittenger et al, 1999; Zuk et al, 2001; Reyes et al, 2002; Safford et al, 2002; Akita et al, 2014)
We evaluated the in vivo potential for periodontal tissue regeneration of rat dedifferentiated fat (DFAT) cells combined with solid PLGA scaffolds in periodontal fenestration defects created in mandibular alveolar bone, and compared the performance of rat DFAT cells in this context with that of adipose-derived stem cells (ASCs)
Calcium accumulation in osteogenic induction medium was significantly higher in DFAT cells than in ASCs at day 14 and 21 (Figure 4B)

Summary

Introduction

The use of adult mesenchymal stem cells (MSCs) seems to be ideal for practical periodontal regenerative medicine, because they are not subject to the restrictions such as embryonic stem cells (ESCs) or induced pluripotent stem cells (Prockop, 1997; Pittenger et al, 1999; Zuk et al, 2001; Reyes et al, 2002; Safford et al, 2002; Akita et al, 2014). ASCs may be a promising cell source for periodontal-tissue regeneration (Tobita et al, 2008; Tobita and Mizuno, 2013; Akita et al, 2014). The utility of ASCs for periodontal tissue regeneration has been demonstrated in rat and canine models in several studies, but successful use of human ASCs for such purpose has not been described yet (Tobita et al, 2008; Tobita and Mizuno, 2013; Akita et al, 2014)

Objectives

Methods

Results

Conclusion