title: Treatment with embryonic stem-like cells into osteochondral defects in sheep femoral condyles.
abstract: BACKGROUND
  Articular 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.
  
  
  RESULTS
  Regenerated 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.
  
  
  CONCLUSIONS
  Histological 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.
authors.affiliation: Department of Animal Science, Agricultural Research Agency of Sardinia, Olmedo, Sassari, 07040, Italy. spilichi@agrisricerca.it.
authors.forename: Susanna
authors.initials: S
authors.lastname: Pilichi
authors.affiliation: Department of Veterinary Medicine, via Vienna, Sassari, 07100, Italy. rocca@uniss.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rocca
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, 77843-4467, TX, USA. rpool@cvm.tamu.edu.
authors.forename: Roy R
authors.initials: RR
authors.lastname: Pool
authors.affiliation: Department of Animal Science, Agricultural Research Agency of Sardinia, Olmedo, Sassari, 07040, Italy. mdattena@agrisricerca.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Dattena
authors.affiliation: Department of Veterinary Medicine, via Vienna, Sassari, 07100, Italy. gemasala@uniss.it.
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Masala
authors.affiliation: Department of Animal Science, Agricultural Research Agency of Sardinia, Olmedo, Sassari, 07040, Italy. l.mara@agrisricerca.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Mara
authors.affiliation: Department of Animal Science, Agricultural Research Agency of Sardinia, Olmedo, Sassari, 07040, Italy. danysanna@tiscali.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Sanna
authors.affiliation: Department of Animal Science, Agricultural Research Agency of Sardinia, Olmedo, Sassari, 07040, Italy. scasu@agrisricerca.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Casu
authors.affiliation: Department of Veterinary Medicine, via Vienna, Sassari, 07100, Italy. lmanu@uniss.it.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Manunta
authors.affiliation: Department of Surgery, Microsurgery and Medicine, University of Sassari, viale San Pietro, Sassari, 07100, Italy. a.manunta@uniss.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manunta
authors.affiliation: Department of Veterinary Medicine, via Vienna, Sassari, 07100, Italy. esp@uniss.it.
authors.forename: Eraldo Sanna
authors.initials: ES
authors.lastname: Passino
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000628:therapy / Q000662:veterinary*; D002358:Cartilage, Articular / Q000254:growth & development / Q000473:pathology; D005260:Female; D005269:Femur / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000662:veterinary*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D012756:Sheep; D012757:Sheep Diseases / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome