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      Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development

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          Abstract

          Introduction

          Micronized dehydrated human amnion/chorion membrane (μ-dHACM) is derived from donated human placentae and has anti-inflammatory, low immunogenic and anti-fibrotic properties. The objective of this study was to quantitatively assess the efficacy of μ-dHACM as a disease modifying intervention in a rat model of osteoarthritis (OA). It was hypothesized that intra-articular injection of μ-dHACM would attenuate OA progression.

          Methods

          Lewis rats underwent medial meniscal transection (MMT) surgery to induce OA. Twenty four hours post-surgery, μ-dHACM or saline was injected intra-articularly into the rat joint. Naïve rats also received μ-dHACM injections. Microstructural changes in the tibial articular cartilage were assessed using equilibrium partitioning of an ionic contrast agent (EPIC-μCT) at 21 days post-surgery. The joint was also evaluated histologically and synovial fluid was analyzed for inflammatory markers at 3 and 21 days post-surgery.

          Results

          There was no measured baseline effect of μ-dHACM on cartilage in naïve animals. Histological staining of treated joints showed presence of μ-dHACM in the synovium along with local hypercellularity at 3 and 21 days post-surgery. In MMT animals, development of cartilage lesions at 21 days was prevented and number of partial erosions was significantly reduced by treatment with μ-dHACM. EPIC-μCT analysis quantitatively showed that μ-dHACM reduced proteoglycan loss in MMT animals.

          Conclusions

          μ-dHACM is rapidly sequestered in the synovial membrane following intra-articular injection and attenuates cartilage degradation in a rat OA model. These data suggest that intra-articular delivery of μ-dHACM may have a therapeutic effect on OA development.

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          Most cited references35

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          The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat.

          During the development of disease-modifying osteoarthritis (OA) drugs, rat models of OA are frequently used for a first assessment of in vivo efficacy. The most efficacious compound in the rat model may then be tested in a larger animal model before entering human trials. The aim of this study was to describe a histologic scoring system for use in different models of OA in rats that allows standardization and comparison of results obtained by different investigators. The experience of the authors with current scoring systems and the range of lesions observed in rat and human OA studies were considered in recommending this common paradigm for rat histologic scoring. Considerations were made for reproducibility and ease of use for new scorers. Additional scoring paradigms may be employed to further identify specific effects of some disease-modifying drugs. Although the described scoring system is more complex than the modified Mankin scores, which are recommended for some other species, the reliability study showed that it is easily understood and can be reproducibly used, even by inexperienced scorers. The scoring paradigm described here has been found to be sufficiently sensitive to discriminate between treatments and to have high reproducibility. Therefore we recommend its use for evaluation of different rat OA models as well as assessment of disease-modifying effects of treatments in these models. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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            Quantification of Bone Microarchitecture with the Structure Model Index.

            The deterioration of cancellous bone structure due to aging and disease is characterized by a conversion from plate elements to rod elements. Consequently the terms "rod-like" and "plate-like" are frequently used for a subjective classification of cancellous bone. In this work a new morphometric parameter called Structure Model Index (SMI) is introduced, which makes it possible to quantify the characteristic form of a three-dimensionally described structure in terms of the amount of plates and rod composing the structure. The SMI is calculated by means of three-dimensional image analysis based on a differential analysis of the triangulated bone surface. For an ideal plate and rod structure the SMI value is 0 and 3, respectively, independent of the physical dimensions. For a structure with both plates and rods of equal thickness the value lies between 0 and 3, depending on the volume ratio of rods and plates. The SMI parameter is evaluated by examining bone biopsies from different skeletal sites. The bone samples were measured three-dimensionally with a micro-CT system. Samples with the same volume density but varying trabecular architecture can uniquely be characterized with the SMI. Furthermore the SMI values were found to correspond well with the perceived structure type.
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              The extracellular matrix as a scaffold for tissue reconstruction.

              The extracellular matrix (ECM) consists of a complex mixture of structural and functional proteins and serves an important role in tissue and organ morphogenesis, maintenance of cell and tissue structure and function, and in the host response to injury. Xenogeneic and allogeneic ECM has been used as a bioscaffold for the reconstruction of many different tissue types in both pre-clinical and human clinical studies. Common features of ECM-associated tissue remodeling include extensive angiogenesis, recruitment of circulating progenitor cells, rapid scaffold degradation and constructive remodeling of damaged or missing tissues. The ECM-induced remodeling response is a distinctly different phenomenon from that of scar tissue formation.
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                Author and article information

                Contributors
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central
                1478-6354
                1478-6362
                2014
                6 February 2014
                : 16
                : 1
                : R47
                Affiliations
                [1 ]George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332-0405, USA
                [2 ]Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332-0405, USA
                [3 ]Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA 30332-0405, USA
                Article
                ar4476
                10.1186/ar4476
                3978824
                24499554
                406c25ef-c5ae-4c53-9b70-4ff8e970b936
                Copyright © 2014 Willett et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 April 2013
                : 27 January 2014
                Categories
                Research Article

                Orthopedics
                Orthopedics

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