Intra-articular Xenotransplantation of Adipose-Derived Stromal Cells to Treat Osteoarthritis in a Goat Model

Abstract

Adipose-derived stromal cells (ASCs) have been investigated as a cell source for tissue regeneration. The purpose of this study was first to confirm if medial meniscectomy induces osteoarthritis (OA) in goats within a relative short period of time, and more importantly, to investigate if systemic treatment with immunosuppressive drugs is necessary in intra-articular ASC xenotransplantation for successful regeneration of articular cartilage and prevention of joint inflammation. Eight Korean native black goats 1-2 years of age underwent medial meniscectomy. To evaluate the gross and histological appearance of articular cartilage, knee joints were re-exposed by a medial parapatellar incision at 8 weeks. After macroscopic scoring of gross appearance, cartilage biopsy specimens 6 mm in diameter were obtained from the femoral condyle in four goats. The goats were injected with single intra-articular dose of 7×10⁶ human ASCs (hASCs) 7 days after the second arthrotomy. Four animals were treated with daily injections of cyclosporin A 10 mg/kg for 7 days, followed by a reduced dose of 5 mg/kg for another 7 days, while other 4 animals did not receive immunosuppressive therapy. All animals were sacrificed for analysis 8 weeks after injection of hASCs. OA was successfully induced 8 weeks after medial meniscectomy. Eight weeks after injection of hASCs, various signs of articular cartilage regeneration were observed. There were no significant macroscopic and histological differences between goats treated with cyclosporine and untreated goats. Interleukin-1ß and tumor necrosis factor-α level from synovial fluid did not differ between cyclosporine-treated and untreated goats. The results indicate that immunosuppressive therapy did not influence the result of ASC xenotransplantation to treat OA.

Keywords: Adipose-derived stromal cell; Articular cartilage; Cyclosporin A; Osteoarthritis; Xenotransplantation.

Fig. 1

The surgical process of medial meniscectomy to induce OA in goat (A), IA injection of hASCs (B)

Fig. 2

Confirmation of the surgically-induced OA in goats. Gross appearance (A) and histological analysis by Safranin-O staining (B) from osteochondral punch biopsy from femoral condyle in 4 goats demonstrates successful OA induction

Fig. 3

The gross observation and macroscopic scoring of articular cartilage after ASC injection with or without immunosuppression. ISD w/: with immunosuppressive drug treatment, ISD w/o: without immunosuppressive drug treatment, NS: not specific

Fig. 4

The determination of inflammatory conditions after ASC injection with or without immunosuppression in the goat medial meniscus model. Measurements of synovial fluid volume (A) and evaluation of IL-6 and TNA-α by ELISA (B). ISD w/: with immunosuppressive drug treatment, ISD w/o: without immunosuppressive drug treatment, NS: not specific