RESUMEN
BACKGROUND: Articular cartilage lacks a regenerative response. Embryonic stem cells (ESCs) are a source of pluripotent cells for cartilage regeneration. Their use, however, is associated with a risk of teratoma development, which depends on multiple factors including the number of engrafted cells and their degree of histocompatibility with recipients, the immunosuppression of the host and the site of transplantation. Colonies of sheep embryonic stem-like (ES-like) cells from in vitro-produced embryos, positive for stage-specific embryonic antigens (SSEAs), alkaline phosphatase (ALP), Oct 4, Nanog, Sox 2 and Stat 3 gene expression, and forming embryoid bodies, were pooled in groups of two-three, embedded in fibrin glue and engrafted into osteochondral defects in the left medial femoral condyles of 3 allogeneic ewes (ES). Empty defects (ED) and defects filled with cell-free glue (G) in the condyles of the controlateral stifle joint served as controls. After euthanasia at 4 years post-engraftment, the regenerated tissue was evaluated by macroscopic, histological and immunohistochemical (collagen type II) examinations and fluorescent in situ hybridization (FISH) assay to prove the ES-like cells origin of the regenerated tissue. RESULTS: No teratoma occurred in any of the ES samples. No statistically significant macroscopic or histological differences were observed among the 3 treatment groups. FISH was positive in all the 3 ES samples. CONCLUSIONS: This in vivo preclinical study allowed a long-term evaluation of the occurrence of teratoma in non-immunosuppressed allogeneic adult sheep engrafted with allogeneic ES-like cells, supporting the safe and reliable application of ES cells in the clinic.
Asunto(s)
Células Madre Embrionarias/trasplante , Fémur/lesiones , Ovinos/lesiones , Animales , Neoplasias Óseas/prevención & control , Neoplasias Óseas/veterinaria , Trasplante Óseo/efectos adversos , Trasplante Óseo/métodos , Trasplante Óseo/veterinaria , Femenino , Fémur/patología , Fémur/cirugía , Estudios de Seguimiento , Hibridación Fluorescente in Situ/veterinaria , Masculino , Ovinos/cirugía , Teratoma/prevención & control , Teratoma/veterinariaRESUMEN
An intact male white pekin duck (Anas platyrhynchos domesticus) was presented for examination because of respiratory distress and 2- to 3-month history of lameness and lethargy. Results of radiography, ultrasonography, and cytologic examination revealed a large neoplastic mass in the coelom. The duck was euthanatized, and results of necropsy revealed 2 large, lobulated masses in the coelom and a small nodule on the liver. Histopathologic examination of the large masses revealed a collision pattern testicular tumor consisting of Sertoli, seminoma, and interstitial cell components. The hepatic nodule was a metastatic lesion consistent with a Sertoli cell testicular tumor. This is the first reported case of a mixed germ cell-sex cord-stromal tumor in a duck.