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Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model
Authors:Manabu Shimizu  Taro Matsumoto  Shinsuke Kikuta  Munenori Ohtaki  Koichiro Kano  Hiroaki Taniguchi  Shu Saito  Masahiro Nagaoka  Yasuaki Tokuhashi
Affiliation:1. Department of Orthopedic Surgery, Nihon University School of Medicine, Tokyo, Japan;2. Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan;3. Laboratory of Cell and Tissue Biology, College of Bioresource Science, Nihon University, Fujisawa, Japan;4. Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland
Abstract:

Background

Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects.

Methods

Full-thickness osteochondral defects were created in the knees of Sprague–Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen.

Results

DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation.

Conclusions

Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries.
Keywords:Corresponding author. Department of Functional Morphology   Division of Cell Regeneration and Transplantation   Nihon University School of Medicine   30-1 Oyaguchi-Kamicho   Itabashi-ku   Tokyo 173-8610   Japan. Fax: +81 33972 8666.
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