الفهرس 
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Abstract
Osteoarthritis is a disorder involving movable joints characterized by cell stress and extracellular matrix degradation initiated by micro-and macroinjury that activates maladaptive repair responses including pro-inflammatory pathways of innate immunity. This in turn manifests initially as abnormal joint tissue metabolism and subsequently by anatomic and physiologic derangements. Clinically, this can present as cartilage degradation, bone remodeling, and osteophyte formation, with joint inflammation, pain, and loss of normal joint function affecting millions of new cases each year worldwide causing disability. The monosodium iodoacetate (MIA) model of osteoarthritis is well established and resembles human degenerative OA. Small animal models of OA (like rats) have many advantages like low cost, ease of handling, and availability of housing, so they have been used routinely to study the degenerative changes in their knees. Preparation of peripheral blood mononuclear cells (PBMNCs) is a safe and cost-effective method as they are isolated from peripheral blood and identified as any blood cell with a slightly indented spherical nucleus. They act as a rich source of paracrine mediators and play a key role in tissue regeneration in persistent trophic lesions through inflammatory macrophages, growth factors and cytokines, as well as through exosomes. Platelet-rich plasma (PRP) is a blood fraction with a platelet concentration of at least one million platelets/μl, or approximately five times higher than that of whole blood (platelet concentrate). Many biological mediators are present in a PRP like Platelet-Derived Growth Factor (PDGF), Insulin-like Growth Factor type I (IGF-I), Transforming Growth Factor β type 1 (TGF-β1), Hepatocyte Growth Factor (HGF), Vascular Endothelial Growth Factor (VEGF), Epithelial Growth Factor (EGF) and basic Fibroblastic Growth Factor (bFGF). They all are very important during tissue repair. The aim of this work was to study the therapeutic effect of peripheral blood mononuclear cells versus platelet-rich plasma on induced osteoarthritis of the knee joint in adult male albino rats by using different histological techniques supported with statistical analysis of the results. This work was carried out on seventy adult male albino rats weighting 120-150 gm. The animals were divided into two major groups: donor group and experimental groups. Donor group: included 20 rats divided into two equal subgroups; one for donation of peripheral blood mononuclear cells and the other for donation of platelet-rich plasma. Experimental groups: included 50 rats and divided into five main groups: ➢ group I: included 10 rats served as a control group and subdivided into: - Subgroup Ia: included 4 rats which did not receive any medication. - Subgroup Ib: included 3 rats which received intra-articular injection of 50 ul sterile saline solution. - Subgroup Ic: included 3 rats which received intra-articular injection of 50 ul phosphate buffered saline solution. ➢ group II: included 10 rats which received single unilateral intra-articular injection of monosodium iodoacetate (MIA) at a dose of 6mg/ kg body weight dissolved in sterile saline solution for induction of osteoarthritis. The rats were sacrificed two weeks later. ➢ Groups III, IV and V received intra-articular injection of MIA at the same dose as group II for osteoarthritis induction. ➢ group III: included 10 rats which received intra-articular injection of 50 ul peripheral blood mononuclear cells [PBMNCs] two weeks after the MIA injection, then sacrificed 3 weeks later. ➢ group IV: included 10 rats which received intra-articular injection of 50 ul platelet-rich plasma [PRP] two weeks after MIA injection, then sacrificed 3 weeks later. ➢ group V: included 10 rats which received single intra-articular injection of monosodium iodoacetate (MIA) and left without treatment for 5 weeks, then sacrificed. At the end of the experiment, the animals were sacrificed, and the knee joints were dissected carefully and processed for light microscopic study after their decalcification. Serial 5um sections were cut and stained with hematoxylin and eosin, Mallory trichrome and Safranin O & Van Gieson’s stains. For histomorphometric assessment & statistical analysis; histopathological grading was performed after examination of H&E-stained sections and Safranin O & Van Gieson’s stains of all animals. In addition, image analysis was performed on the Mallory trichrome stained sections for evaluation of collagen fiber content. Moreover, the thickness of articular cartilage and the underlying subchondral bone were estimated by image analysis and the data were statistically analyzed. The articular cartilage of tibia from each group was taken and immediately fixed in glutaraldehyde solution then prepared for the scanning electron microscope. The results of this study were recorded and could be summarized as follows: Haematoxylin & Eosin stained sections: - group I (Control group): revealed a normal microscopic structure of the knee joint including capsule, synovial membrane, articular cartilage, subchondral bone, menisci and patella. - group II (Osteoarthritis group): revealed severe histological alteration in the form of loss of joint architecture evidenced by thinning of heterogenously stained hypocellular articular cartilage that was eroded and replaced by fibrous tissue or bone marrow cavities with loss of zonal arrangement of its cells. The meniscus was thin distorted with an irregular joint cavity and narrowing of the joint space. The synovial membrane and fibrous joint capsule were thickened. The subchondral bone showed destructed plate and trabeculae. - group III (PBMNCs treated group): showed disappearance of most of the osteoarthritic features especially the articular cartilage surface, thickness, and cellular content with restoration of articular cartilage structure and thickness. The structure of the meniscus and the subchondral bone plate, as well as the trabeculae were preserved as those observed in the control group. The joint space was restored to be near normal while the fibrous joint capsule was slightly thickened. As regards the synovial membrane it was thickened with dilated and congested blood vessels. - group IV (PRP treated group): displayed preservation of joint structures in some fields and persistence of osteoarthritic features in others. The articular cartilage was regular in some sections whereas in others there were irregularities and erosions as well as bone marrow cavities in its structure. Normal joint space was also observed. At the same time, the subchondral bone thickness was apparently increased while the meniscus was locally eroded. The synovial membrane was thick with proliferation of its cells and adherent to the surface of the articular cartilage in some areas. - group V (Recovery group): showed progressive pathological changes of osteoarthritis in all parts of the knee joint specifically destructed articular cartilage and the appearance of osteophytes. The articular cartilage was a thin rim in some areas while in others it was completely absent. Different clusters of cells were noticed in the substance of the articular cartilage, some of them consisted of chondrocytes while others consisted of cells with multiple thin processes. Multiple fissures were also noticed in the calcified cartilage zone that was bounded by a deeply basophilic well-defined tidemark line as well as the synovial membrane was thickened. As regards the meniscus changes, it was deformed, acellular with loss of collagen fiber organization. Concerning the subchondral bone, it displayed cavitation with overlying fibrillated articular cartilage in some areas or fibrous tissue in others. Multiple bony extensions replacing the lower surface of the articular cartilage forming different sizes of ossification nodules were observed. Occasionally it revealed multiple basophilic cement lines, minor cracks, transverse splitting between it and the overlying articular cartilage remnants as well as fractured trabeculae were also noticed. While in some sections, cartilage islands were observed in the subchondral bone and beneath the osteophytes.