The Role of Erythropoietin and Bone Marrow Concentrate in the Treatment of Osteochondral Defects in Mini-Pigs

Marcel Betsch,Monika Herten,Michael Wild,Pascal Jungbluth,Simon Thelen,Daniel Miersch,Mohssen Hakimi,Laila Santak,Nuno M Neves

doi:10.1371/journal.pone.0092766

Abstract

BackgroundAll available treatment options for osteochondral and chondral defects do not restore hyaline cartilage and are limited to decreasing associated pain, and maintaining or improving joint function. The purpose of this study was to evaluate the potential of erythropoietin (EPO) in combination with bone marrow aspiration concentrate (BMAC) in the treatment of osteochondral defects of mini-pigs.Methods14 Goettinger mini-pigs, in which a 6×10 mm osteochondral defect in the medial femoral condyle of both knee joints was created, were randomized into four groups: biphasic scaffold alone, scaffold with EPO, scaffold with BMAC and scaffold in combination with EPO and BMAC. After 26 weeks all animals were euthanized and histological slides were evaluated using a modified ÓDriscoll Score.ResultsIn the therapy groups, areas of chondrogenic tissue that contained collagen II were present. Adding EPO (p = 0.245) or BMAC (p = 0.099) alone to the scaffold led to a non-significant increase in the score compared to the control group. However, the combination of EPO and BMAC in the implanted scaffold showed a significant improvement (p = 0.02) in the histological score.ConclusionThe results of our study show that in mini-pigs, the combination of EPO and BMAC leads to an enhanced osteochondral healing. However, additional research is necessary to further improve the repair tissue and to define the role of MSCs and EPO in cartilage repair.

Highlights

Surgical attempts to restore articular cartilage lesions have focused on the recruitment of stem cells by puncturing the subchondral bone to allow bone marrow to flow into the lesions and initiate healing [1]
Animal model and surgery All mini-pigs were acclimated for one week before the surgery, and the defects in all animals were randomized into the following four treatment groups: scaffold alone, scaffold combined with bone marrow aspiration concentrate (BMAC), scaffold combined with erythropoietin (EPO) and scaffold combined with EPO and BMAC (EPO+BMAC) using a sealed envelope system (Table 1)
In vitro analysis The quality of BMAC was evaluated by a calculation of the concentration factor of mononuclear cells in BMAC, the formation of colony forming units, and a cell characterization using FACS analysis of the Mesenchymal stem cells (MSCs) within BMAC

Summary

Introduction

Surgical attempts to restore articular cartilage lesions have focused on the recruitment of stem cells by puncturing the subchondral bone to allow bone marrow to flow into the lesions (microfracture) and initiate healing [1]. Cell-based therapies such as autologous chondrocyte implantation (ACI), have been developed to treat cartilage and osteochondral lesions [2]. These techniques require two surgical procedures, one to harvest the cartilage tissue from a non-weight bearing, unaffected area and a second to implant the cells after their expansion in vitro [3]. The development of a single-step, simple, autologous, and cost-effective cartilage repair technique is desirable [6]. All available treatment options for osteochondral and chondral defects do not restore hyaline cartilage and are limited to decreasing associated pain, and maintaining or improving joint function. The purpose of this study was to evaluate the potential of erythropoietin (EPO) in combination with bone marrow aspiration concentrate (BMAC) in the treatment of osteochondral defects of mini-pigs

Objectives

Methods

Results

Conclusion