Syed Zamin

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 hips^1-2. 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 obesity^3-4. 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 joints^5-6. 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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