Autologous Adipose-Derived Stem Cell Sheet Has Meniscus Regeneration-Promoting Effects in a Rabbit Model

Abstract

This study investigated meniscal regeneration-promoting effects of adipose-derived stem cell (ADSC) sheets in a rabbit meniscal defect models. ADSCs were extracted from the interscapular fat pad adipose tissue of 42 mature female Japanese white rabbits. Once cells reached confluence at the third passage, the culture medium was supplemented with ascorbic acid. Within a week, the cells in culture formed removable sheets, which were used as ADSC sheets. Cell death (CD) sheets were created by killing ADSCs by freezing to investigate the need for viable ADSCs in ADSC sheets. The anterior half of the medial meniscus from the anterior root to the posterior edge of the medial collateral ligament was removed from both limbs. An autologous ADSC or CD sheet was transplanted to one knee (ADSC sheet or CD sheet group). The contralateral limb was closed without transplantation following meniscal removal (control group). Rabbits were euthanized 4 and 12 weeks after transplantation to harvest the entire medial menisci. The meniscal tissue area, transverse diameter on the inside of the medial collateral ligament, and histologic score were compared between the 3 groups. The area and transverse diameter of regenerated tissues were larger in the ADSC sheet group than in the control group at 4 and 12 weeks. Further, the histologic score in the ADSC sheet group (8) was significantly greater than that in the control group (4.5) at 4 weeks (P= .02) and greater than that in the CD sheet group (9) (ADSC= 12.5, P= .009) and control group (6) (ADSC= 12.5, P= .0003) at 12 weeks. Transplantation of the ADSC sheet into the meniscal defect increased the volume and improved the histologic score of the regenerated meniscal tissue. ADSC sheets may have meniscal regeneration-promoting effects in a rabbit model with meniscal defects. ADSC sheets do not require a scaffold for implantation in the rabbit model, and this evidence suggests that some tissue regeneration occurs at the site of a surgically created meniscal defect.