Treatment with embryonic stem-like cells into osteochondral defects in sheep femoral condyles

Abstract

BackgroundArticular cartilage has poor intrinsic capacity for regeneration because of its avascularity and very slow cellular turnover. Defects deriving from trauma or joint disease tend to be repaired with fibrocartilage rather than hyaline cartilage. Consequent degenerative processes are related to the width and depth of the defect. Since mesenchymal stem cells (MSCs) deriving from patients affected by osteoarthritis have a lower proliferative and chondrogenic activity, the systemic or local delivery of heterologous cells may enhance regeneration or inhibit the progressive loss of joint tissue. Embryonic stem cells (ESCs) are very promising, since they can self-renew for prolonged periods without differentiation and can differentiate into tissues from all the 3 germ layers. To date only a few experiments have used ESCs for the study of the cartilage regeneration in animal models and most of them used laboratory animals. Sheep, due to their anatomical, physiological and immunological similarity to humans, represent a valid model for translational studies. This experiment aimed to evaluate if the local delivery of male sheep embryonic stem-like (ES-like) cells into osteochondral defects in the femoral condyles of adult sheep can enhance the regeneration of articular cartilage. Twenty-two ewes were divided into 5 groups (1, 2, 6, 12 and 24 months after surgery). Newly formed tissue was evaluated by macroscopic, histological, immunohistochemical (collagen type II) and fluorescent in situ hybridization (FISH) assays.ResultsRegenerated tissue was ultimately evaluated on 17 sheep. Samples engrafted with ES-like cells had significantly better histologic evidence of regeneration with respect to empty defects, used as controls, at all time periods.ConclusionsHistological assessments demonstrated that the local delivery of ES-like cells into osteochondral defects in sheep femoral condyles enhances the regeneration of the articular hyaline cartilage, without signs of immune rejection or teratoma for 24 months after engraftment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0301-9) contains supplementary material, which is available to authorized users.

Regeneration of Articular Cartilage by Human ESC-Derived Mesenchymal Progenitors Treated Sequentially with BMP-2 and Wnt5a

“…However, a major limiting factor to using adult mesenchymal stem cells for cartilage repair in the clinic has been the variable capacity of somatic cells to regenerate permanent cartilage , . To this end, various groups have explored the use of pluripotent stem cells for cartilage repair , , , , . Specifically, multiple methods have been proposed to derive chondrocytes from human embryonic and induced pluripotent stem cells , .…”

Animal Models of Osteochondral Defect for Testing Biomaterials

“…Gotterbarm et al [25] showed that 6.3 mm diameter OCD did not spontaneously heal in mini-pig, confirming the applicability of this pig breed to articular cartilage research. e large majority of the cartilage regeneration studies in the mini-pig are performed on the joint knee, involving the medial [66] or femoral condyles [67,68], or femoral trochlea. Generally, 6 mm to 8 mm diameter or larger dimensions OCD are created, and the postoperative follow-up period is usually between 3 and 24 months (Table 5).…”

“…e cartilage thickness of the medial femoral condyle is approximately 0.45 mm. e location of the cartilage defects in the sheep model has involved the medial femoral condyle [67,70,71], both femoral condyles [72,73], and the femoral trochlea [70]. OCD with a diameter of 6-8 mm and a depth of 5-13 mm were used for the assessment of biomaterial strategies ( Table 6).…”

Current and novel injectable hydrogels to treat focal chondral lesions: Properties and applicability

“…(25) When allogenic ESCs seeded in fibrin glue were applied for treating induced knee focal osteochondral defects in sheeps, these were efficiently repaired with better outcomes (higher collagen II and proteoglycans) than the untreated control joints. (26) While promising, ESCs are associated with ethical concerns surrounding their derivation, limiting their use. (27) This has promoted significant interest in adult-derived stem cells such as MSCs, a multipotent cell population and precursor of cartilage.…”

“…Most of these studies suggest promising results with improved cartilage regeneration between 3 months and 2 years. 26,[32][33][34][35][36] Significant superior histologic evidence of cartilage regeneration when using hydrogels are reported when compared to empty defects. The cell sources, collection techniques, cell processing, qualitative and quantitative characterizations, and delivery methods vary widely between studies.…”