الفهرس 
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Abstract
Osteoarthritis (OA) is a group of mechanical abnormalities involving degradation of joints including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness,locking, and sometimes an effusion. A variety of causes—hereditary, developmental, metabolic, and mechanical—may initiate processes leading to loss of cartilage. When bone surfaces become less well protected by cartilage, bone may be exposed and damaged. As a result of decreased movement secondary to pain, regional muscles may atrophy, and ligaments may become more lax.
Treatment generally involves a combination of exercise, lifestyle modification, and analgesics. If pain becomes debilitating, join replacement surgery may be used to improve the quality of life.
Stem cell therapy holds a great promise for the repair of injured tissues and organs, including articular join diseases. The bone marrow (BM) contains at least two populations of stem cells, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), which provide stromal support for HSCs. It also contains many other hematopoietic cell types involved in immune surveillance inflammatory responses and pathogen removal. It has long been proposed that bone marrow, a known source of stem cells, might be able to contribute to the repair of other organs.
The MSC are undifferentiated adult SC of mesodermal origin that have the capacity to be differentiated into cells of connective tissue lineages, including bone , fat, cartilage and muscle.
Several studies also demonstrated that MSC are nonimmunogenic and display immunosuppressive properties, with the ability to inhibit maturation of dendritic cells and to suppress the fraction of memory T cells, B cells and NK cells. These properties of MSC render these cells especially attractive for therapeutic application in several inflammatory and immune-mediated diseases, as well as in regenerative medicine.
The high prevalence of osteoarthritis in Egypt indicate the need for modern alternative therapeutic modalities. In this work, the protective effects isolated bone marrow derived mesenchymal Stem cells was studied in an experimentally induced osteoarthritis rabbit model.
The study was carried on 20 New Zealand white rabbits; of an average weight 1000-1500 gm. The rabbits were divided into 6 groups as follow:
Group 1 (control group): two rabbits.
Group 2: (n=3) three rabbits which were injected by phosphate buffer as -ve control.
Group 3: (n=3) three rabbits which were injected by stem cells.
Group 4: (n=6) six rabbits which were injected by LPS
Arthritis was induced by intra-articular injection of three times of lipopolysaccharide (LPS) at day 0, 4 and 8 at 4-day intervals into the knee joints of rabbits.
Group 5: (n=3) 3 rabbits which were injected by LPS then treated after one week by 0.25ml of 5 x 106 stem cells.
Group 6: (n=3) 3 rabbits which were injected prophylactically by stem cells then by LPS.
Serum CRP was used to evaluate the joint inflammatory condition. TNF-α, TGF B and CTGF gene expression were measured by RT-PCR to interpret the mechanism of action of MSC while CD 29 and CD 166 gene expression was done as a molecular marker for MSC. MSCs were labeled with PKH26 dye to detect their homing into the knee tissue. Histopathology with H&E stains were done to recognize the changes in the knee join in the different studied groups.
The results of this study showed that there is a significant improvement in serum CRP concentration with MSC therapy, significant decrease of the pro-inflammatory TNF-α and there was a significant increase in TGFβ and CTGF gene expression.
The MSCs were detected in the knee tissue as red fluorescence when labeled with PKH26 dye.
The histopathology examination of the study group of OA treated with MSCs showed that the cavity of the knee joint with the synovial membrane and the bones of the femur & tibia appear with normal architecture and coverd with cartilage of normal thickness with increased areas of fibrous tissue formation.
Conclusion
In conclusion, MSC can exert beneficial effect on OA possibly by a paracrine mechanism through regulation of inflammatory cytokines such as TNF-α and growth factors such as TGF-β and CTGF.
Recommendations
1- Isolation of MSCs and their propagation is an essential tool for the progress of medical research and provides a way through which tissue regeneration and engineering could be used in Medicine.
2- The identification of the isolated cells and their propagation is a costly process that needs continuous funding.
3- MSCs infusion may prove to be a supplement or adjuvant to joint replacement.
4- Comparison of the work with undifferentiated and differentiated MSCs has to be done with the knowledge that differentiated cells have fixed cell cycle duration and are more liable to apoptosis.
5- Studying if MSCs can regenerate knee tissues and transdifferentiate to any of its components