Sheep embryonic stem-like cells transplanted in full-thickness cartilage defects

Abstract

Articular cartilage regeneration is limited. Embryonic stem (ES) cell lines provide a source of totipotent cells for regenerating cartilage. Anatomical, biomechanical, physiological and immunological similarities between humans and sheep make this animal an optimal experimental model. This study examines the repair process of articular cartilage in sheep after transplantation of ES-like cells isolated from inner cell masses (ICMs) derived from in vitro-produced (IVP) vitrified embryos. Thirty-five ES-like colonies from 40 IVP embryos, positive for stage-specific embryonic antigens (SSEAs), were pooled in groups of two or three, embedded in fibrin glue and transplanted into osteochondral defects in the medial femoral condyles of 14 ewes. Empty defect (ED) and cell-free glue (G) in the controlateral stifle joint served as controls. The Y gene sequence was used to detect ES-like cells in the repair tissue by in situ hybridization (ISH). Two ewes were euthanized at 1 month post-operatively, three each at 2 and 6 months and four at 12 months. Repairing tissue was examined by biomechanical, macroscopic, histological, immunohistochemical (collagen type II) and ISH assays. Scores of all treatments showed no statistical significant differences among treatment groups at a given time period, although ES-like grafts showed a tendency toward a better healing process. ISH was positive in all ES-like specimens. This study demonstrates that ES-like cells transplanted into cartilage defects stimulate the repair process to promote better organization and tissue bulk. However, the small number of cells applied and the short interval between surgery and euthanasia might have negatively affected the results.

Autologous cartilage fragments in a composite scaffold for one stage osteochondral repair in a goat model

“…In the literature, different studies have proposed a cell labelling technique to assess the location and the role of specific cell populations at the defect site, but this seems to be somehow impractical for our repair model, dealing with cartilage fragments embedded in a composite scaffold as a source of cells for the repair. On the other hand, a male source of fragments implanted in a female host could represent a possible solution to that issue, due to the possibility to detect cells carrying the Y gene sequence in the repair tissue by in situ hybridisation, as suggested by recent work of Dattena et al (2009). Indeed, the use of scaffold with allogeneic chondral fragments transplanted to recipients of different gender may constitute an alternative to identify the position of the migrating chondrocytes in the repair tissue and to discriminate this particular cell population from the recipient cells of the surrounding tissue.…”

Neonatal Desensitization Supports Long-Term Survival and Functional Integration of Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells in Rat Joint Cartilage Without Immunosuppression

“…Previous studies have reported that implantation of ESCs or ESC-derived chondrogenic cells promoted cartilage repair in vivo [4][5][6]. However, it is difficult to obtain autologous ESCs for cell transplantation, and an immunologic barrier prevents in vivo long-term engraftment and function of allogenous ESCs [7].…”

Current perspectives in stem cell research for knee cartilage repair

“…Embryonic stem cells and induced pluripotent stem cells may provide universal, unlimited sources of cells with reparative and regenerative capabilities for cartilage lesions because they have a potential for indefinite undifferentiated proliferation and can be induced towards chondrocyte differentiation 100–107. Embryonic stem cells have already been used to enhance the healing of cartilage defects in vivo108–110 and to allow for the production of a cartilage matrix capable of integrating with defects in human arthritic joint cartilage 111. However, use of embryonic stem cells remains largely controversial for ethical reasons to do with the harvesting of cells from human embryos, and due to safety issues because their use is associated with immune rejection problems and with the formation of teratomas 112.…”