Scaffold-Free Tissue-Engineered Allogenic Adipose-Derived Stem Cells Promote Meniscus Healing.
OBJECTIVE
To determine whether meniscal tissue could be healed histologically by the implantation of allogenic three-dimensional formed adipose-derived stem cells (ADSCs) in a rabbit model of partial meniscectomy.


METHODS
Forty Japanese white rabbits (aged 15-17 weeks) were assigned to 2 groups. Defects 1.5 mm in diameter were created in the anterior horn of the medial menisci. The defects were left empty in the control group and were filled with cylindrical plugs of allogenic ADSCs extracted from adipose tissue in the experimental group. Macroscopic scoring (range, 0-3), histological scoring (range, 0-12), and immunohistological stainability of type I collagen were evaluated at 2, 4, 8, and 12 weeks postoperatively (n = 5 rabbits for each week).


RESULTS
Macroscopically, the height of the healing tissue in the experimental group was significantly greater than that of the control group at 2 weeks (3 vs 0, P = .01), 4 weeks (3 vs 1, P = .01), and 8 weeks (3 vs 2, P = .02). Histologically, safranin-O staining was noted at 2 weeks and increased gradually over time in the experimental group. In contrast, the intensity of staining was lower in controls at all weeks. Tissue quality scores were significantly higher in the experimental group than in the controls at all weeks (3 vs 0 at 2 weeks [P = .00009], 4.5 vs 2 at 4 weeks [P = .00023], 9 vs 5 at 8 weeks [P = .0047], 10.5 vs 6 at 12 weeks [P = .00026]). The implanted tissue was positive for type I collagen, and stainability was increased gradually over time.


CONCLUSIONS
Three-dimensional scaffold-free allogenic ADSCs implanted into a 1.5-mm avascular meniscal defect survived, adhered to the defect, and promoted histological meniscus healing in a rabbit model.


CONCLUSIONS
ADSC implantation designed to promote meniscal healing may play an important role as a tool for meniscus healing.
Department of Orthopaedic Surgery, Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan.
Tatsuhiro
T
Toratani
Department of Orthopaedic Surgery, Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: nakase1007@yahoo.co.jp.
Junsuke
J
Nakase
Department of Orthopaedic Surgery, Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan.
Hitoaki
H
Numata
Department of Orthopaedic Surgery, Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan.
Takeshi
T
Oshima
Department of Orthopaedic Surgery, Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan.
Yasushi
Y
Takata
Department of Orthopaedic Surgery, Graduated School of Medical Science, Kanazawa University, Kanazawa, Japan.
Koichi
K
Nakayama
Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Saga, Japan.
Hiroyuki
H
Tsuchiya
D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D005260:Female; D023421:Models, Animal; D011817:Rabbits; D033581:Stem Cell Transplantation; D000070600:Tibial Meniscus Injuries / Q000601:surgery*; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous; D014945:Wound Healing