Mesenchymal Stem Cell Therapy for Knee Osteoarthritis

Inclusion Criteria

• •1. The subject must be willing and able to provide written informed consent.
• •2. Healthy, non-smoking, males and females.
• •3. Negative Pregnancy test.
• •4. Body weight \> 45 kg and Body Mass Index (BMI) between 18 and 40 kg/m2 (i.e., subjects with a BMI \>40 and \<18 will be excluded).
• •5. No clinically significant abnormal findings on blood pressure, heart rate, physical examination, clinical laboratory tests, or Electrocardiogram (ECG). See details below:
• •1. Heart Rate (HR) \>60 and \<100 bpm
• •2. Systolic Blood Pressure (BP) \>90 and \<170 mmHg
• •3. Diastolic BP \>60 and \<80 mmHg
• •4. Pulse oximetry ≥95% at room air
• •5. Temperature: normal
• •6. Laboratory measures within normal range
• •7. Liver enzymes \<2 x Upper Limit of Normal (ULN)
• •8. Normal bilirubin
• •9. Normal Pain Threshold (PT) / International Normalized Ratio (INR)
• •10. Estimated Glomerular Filtration Rate (eGFR) \>60 ml/min
• •11. Normal ECG.
• •6. Individuals 18 to 80 years old that have knee Osteoarthritis.
• •7. X-rays that demonstrate OA with the Kellgren-Lawrence grading scale of 2, 3 or 4 in at least one compartment of the knee either or both knees. Only subjects that have a single symptomatic knee will be enrolled.
• •8. No significant Medial Collateral Ligament (MCL) or Lateral Collateral Ligament (LCL) tear or laxity. (A significant LCL and MCL laxity or tear would be determined on clinical exam if there is no endpoint on valgus or Varus stress physical exam. Upon review of the MRI, NGRM will only treat subjects with no grade 2 or grade 3 ligamentous sprains \[LCL, MCL, Anterior Cruciate Ligament (ACL), Posterior Cruciate Ligament (PCL)\]. Next Generation Regenerative Medicine (NGRM) will treat subjects with degenerative meniscal changes in tears but no acute or large bucket handle tears.)
• •9. No significant meniscal tear. (i.e. bucket handle) (A positive McMurrays test on clinical exam indicates a significant meniscal tear. The subjects will also be getting a baseline MRI that will help delineate any further ligament injuries that may disqualify a subject.)
• •10. Subjects who have had the benefit of standard of care (SOC) treatment (activity modification, weight loss, physical therapy, anti-inflammatory medications, or injection therapy) before receiving experimental therapy. However, subjects cannot have had the benefit of standard of care treatment at less than 3 months before receiving experimental therapy. Enroll subjects who have demonstrated failure or are intolerant to SOC treatment. The time frame prior to screening when failure of conservative treatment would have occurred will be one year of symptoms and failure of conservative treatment which includes physical therapy, nonsteroidal anti-inflammatory medicine, cortizone injections, or hyaluronic acid injections.
• •1. Treatment failure is indicated by Subjects having symptoms of knee pain, swelling, and trouble with activities for at least 4 to 6 weeks. Subjects would only be enrolled if they fail conservative treatment. Usually physical therapy is administered initially for 6 weeks along with an NSAID medication. If that fails, which means that pain and swelling and disability continue, then injection therapy with corticosteroid or hyaluronic acid (HA) is given. Usually the injection is followed up in 6 to 8 weeks post-injection. If that fails, then Orthobiologics will be discussed (at about 4 to 6 months after treatment).
• •2. The subject must fail at least two conservative treatments, which could include physical therapy and NSAIDs, or physical therapy and injections, or NSAIDs and injections.
• •11. Subjects must have WOMAC and VAS scores of ≥30 and ≥4, respectively at least 2 weeks prior to enrollment.
• •12. Male and female subjects of reproductive potential must agree to refrain from sexual activity or use effective birth control for a duration of one week before and three months after initiation of treatment with either active treatment modality.
• •13. Subjects with basal cell, in situ carcinoma, or remote history (i.e., \> 3 years ago) history of low-grade cancers (e.g., breast) that were effectively treated may be included.