Hypoxia Induced Mesenchymal Stem Cells: The Treatment of Osteoarthritis
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 proliferation2,3. 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 3rd 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 ossification5,6. 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-β34,7. Producing a hypoxic environment increases the production of cartilage, which can be utilized in vivo to treat OA5,6. 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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