Michael Boyd

Introduction: Osteoarthritis (OA) is a disease that arises from the deterioration or absence of cartilage in a joint. The resultant joint has 2 boney surfaces rubbing against one another, resulting in inefficient and painful movement for the patient¹. The 2 bones then frequently undergo aberrant subchondral bone remodeling, making the problem worse. OA primarily affects people greater than 65 years-old and is positively correlated with obesity. With the aging population and obesity epidemic, the prevalence of OA is expected to increase¹. No current treatment options are available to reverse OA. However, mesenchymal stem cells (MSCs) have been shown in several studies to develop into chondrocytes and can cause existing chondrocytes in nearby areas to undergo proliferation^2,3. Furthermore, allogenic MSCs have been shown to be safe when injected into human patients⁴. Recent studies show hypoxic environments induce pathways that have been linked to increased chondrogenesis⁵. These studies could provide a new treatment option for OA. Methods: Cartilage was debrided from patients in an arthroscopic knee procedure and was used to create autologous chondrons (recycled chondrocytes). MSCs were taken from two 3^rd party candidates. The MSCs and chondrons were placed inside the knee joint of a patient via a fibrin glue. A blood sample was taken at 6 weeks post-surgery, and an MRI and second arthroscopy were performed at 1 year post implantation⁴. MSCs were grown in 2 different environments, a hypoxic (2.5% oxygen) and normoxic (21% oxygen) environment. The cells were then analyzed for the production of articular cartilage⁵. Results: Both the MRI and arthroscopy showed an increase in the amount of proteoglycan (a major component of cartilage). At 12 months post-surgery, no MSCs were present in the tissue. A 6-week blood test was performed and showed minimal inflammatory involvement⁴. Hypoxic conditions induced the HIF-1 alpha pathway, resulting in upregulation of Sox 9, causing increased cartilage production, while normoxic conditions caused increased endochondral ossification^5,6. Conclusion: MSCs provide a new option in the treatment of OA. They have been shown to increase cartilage production in recycled chondrocytes in a paracrine fashion by releasing growth factors such as BMP-7 and TGF-β3^4,7. Producing a hypoxic environment increases the production of cartilage, which can be utilized in vivo to treat OA^5,6. The destruction of cartilage through years of wear and tear use, obesity, and trauma cannot only be stopped, but reversed using MSCs.

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