Chrondrogenesis of Mesenchymal Stem Cells for the Treatment of Osteoarthritis
Introduction. Osteoarthritis (OA) is a chronic condition due to the inflammation of synovium and breakdown of cartilage in joints which mainly affects the knees and hips1-2. It has a lifetime prevalence of 40% in males and 47% in females and is steadily increasing due to increased life expectancy and a more sedentary lifestyle leading to increased obesity3-4. The incidence of OA rises sharply after the age of 50 and generally peaks at the age of 70 for both sexes alike3. Studies have shown that altered chondrocyte homeostasis prevents the efficient repair of damaged cartilage, causing excess degradation through the production of matrix metalloproteases (MMPs)2. There are numerous ways to negate the effect of chondrocyte degradation and the progression of OA as found in literature. One method involves preventing large-scale bone reformation to decrease growth factor release by subchondral bone. Another method involves stem cell differentiation into chondrocytes. The latter method allows for the anti-inflammatory properties of mesenchymal stem cells (MSCs) to be coupled with the appropriate cell lineage differentiation and proliferation, restoring normal conditions to joints5-6. Methods. To demonstrate anti-inflammatory properties of MSCs, human bone marrow MSCs were suspended in complete culture medium (CCM) to form spheroids. The spheroid culture was then boiled and cooled to denature spheroid-secreted proteins, and the samples were assayed for PGE2 using ELISA and for anti-inflammatory activity in macrophage assay5. To demonstrate chondrogenesis efficacy, bovine and rabbit MSCs were plated on scaffolds as part of co-cultures with articular chondrocytes (AC) at 1:1 or 1:3 AC-to-MSC ratios. Biopsies of the scaffolds were harvested at 0, 14, and 28 days6. Results. ELISA studies of the spheroid cultures showed large amounts of PGE2 present in solution. PGE2 has been shown to have anti-inflammatory effects, as proven by abolishing the anti-inflammatory effects through an inhibitor of COX-2, through siRNAs for COX-2, and through antibodies for PGE25. All bovine and rabbit scaffold samples showed an increase in cellularity with bovine 1:1 co-cultures showing the greatest improvement. GAG synthesis was greatest in all of the co-cultures compared to pure AC cultures. The 28 day co-cultures showed gene expression levels for aggrecan and collagen types I and II to be greater than those of pure AC cultures6. Conclusion. Chondrogenesis of MSCs can benefit patients suffering from OA in two manners. The anti-inflammatory effects of MSCs can reduce synovial inflammation and the chondrogenesis can help restore lost mass of cartilage.
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