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Abstract
As the single cellular component in adult articular cartilage, chondrocytes are responsible for maintaining the ECM components in a low-turnover state. The composition and organization of matrix macromolecules, unique to this tissue, are determined during chondrocyte differentiation in embryonic and postnatal development of cartilage.
Adult chondrocytes exist in a hypoxic environment within articular cartilage. They are inactive metabolically, partially as a result of an absence of blood vessels and nerves, and display a rounded morphology that reflects their quiescent state.Under physiologic conditions, the adult articular chondrocyte maintains a stable equilibrium between the synthesis and the degradation of matrix components. Adult chondrocytes have a poor capacity for mediating effective repair of extensive cartilage lesions, and this capacity declines with age.
Age-related changes in chondrocyte function decrease the ability of the cells to maintain the tissue, including decreased synthetic activity, synthesis of smaller and less uniform aggrecan molecules and less functional link proteins, and decreased responsiveness to anabolic growth factors.
Osteoarthritis (OA) the most common form of joint disease, is characterized by degeneration of the articular cartilage and, ultimately, joint destruction. The burden of OA is exacerbated by the inadequacies of current therapies. Non-pharmacologic and pharmacologic treatments are used for early and moderately early cases of OA, but protection of articular cartilage has so far not been convincingly shown.
Osteoarthritis, although classically conceived of as a degenerative consequence of aging, is a disease with an increasingly well-characterized molecular pathophysiology. Early, anabolic changes, characterized by proliferation of chondrocytes and increased matrix production, are followed by a predominantly catabolic state, characterized by decreased matrix synthesis, increased proteolytic degradation of matrix, and chondrocyte apoptosis.
Human umbilical cord blood (hUCB) may prove to be a new source of Mesenchymal stem cells (MSCs) for cellular therapeutics for cartilage repair. Also it is a very promising source in Egypt because of the high birth rate. The (hUCB) MSCs have many advantages because of the immaturity of newborn cells compared with adult cells also could be more convenient for cell transplantation and be an economical source of MSCs. Furthermore, hUCB provides no ethical problems for basic studies and clinical applications.
This thesis was carried out to study the effect of intra-articular injection of human umbilical cord blood (hUCB) mesenchymal stem cells (MSCs) in cartilage repair and to evaluate the healing of the articular cartilage by histopathological and ultra structural assessment.
We conducted our study on 20 adult rats
Induction of cartilaginous defect in both knee joints by scratching the cartilage using a sterile needle was done to all rats.
Two of the rats were killed after one week and after 4 weeks of scratching, we examined the knee joint histopathologically to assess the efficacy of scratching to induce cartilage defect, which was apparent after 1 week, but osteoarthritis was obvious after 4 weeks.
After 6 weeks of scratching injection of hUCB MSCs suspended in Hyaluronic acid solution was done in the right knee of each rat and the left knee served as a control.
16 of the animals were killed after 6-8 weeks of injection and knee joints were removed.
Histopathogical evaluation was done to all of the cases using histologic grading scale.
Electron microscopic study was done to one of the injected cases to examine the ultrastructure of the newly formed cartilage.
The two remaining animals are still living for further investigations.
The present study revealed:
In the injected knees:
In 87.5% of the cases the defect filled with repair tissue that was typical hyaline to hyaline like in character.
In 12.5% of the cases the repaired tissue appeared typical fibrocartilage.
The electron microscopic pictures showed well repaired hyaline cartilage and no apoptotic nor necrotic pictures for the chondrocytes.
In the control knees:
The newly formed tissue was an undifferentiated connective tissue, covered with a thin layer of fibrous irregular tissue.