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.

Highlights

  • Articular cartilage has poor intrinsic capacity for regeneration because of its avascularity and very slow cellular turnover

  • Embryonic stem cells (ESCs) are able to self-renew for prolonged periods without differentiation and, most importantly, to differentiate into a large variety of tissues derived from all 3 germ layers [35,36,37,38]

  • Only 17 animals were included in the statistical analysis, because 5 sheep died from toxaemic gastroenteritis after breaking through paddock fencing and freely consuming grass covered with frost

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Summary

Introduction

Articular cartilage has poor intrinsic capacity for regeneration because of its avascularity and very slow cellular turnover. 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. Considering that in certain degenerative diseases, autologous stem cells are depleted and have reduced proliferative capacity and chondrogenic ability [20,21], the delivery of heterologous cells may enhance regeneration or inhibit the progressive loss of joint tissue [20,21]. The larger size and weight of adult sheep, which place greater weight-bearing loads on the healing site, as well as the structural, biochemical, physiological and immunological similarities to man and the ease and low cost of their management with respect to other species, make sheep an optimal experimental model for future clinical applications in humans [50,56]

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