Impact of Mesenchymal Stem Cells in Knee Osteoarthritis

Inclusion Criteria:

Knee Osteoarthritis Subjects

1. Male or female 18-60 years of age

2. Confirmed diagnosis of knee osteoarthritis based on clinical and radiographicfindings

3. Unilateral chronic knee pain >4 months

4. Imaging findings consistent with mild-moderate generalized cartilage degeneration (MRI chondropathy or radiographic changes)

5. Failed non-invasive modalities of treatment

6. Subjects must have the ability to understand and the willingness to sign a writteninformed consent document

7. For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use a contraceptive method with a failure rate of <1%per year during the treatment period. A woman is considered to be of childbearingpotential if she is postmenarcheal, has not reached a postmenopausal state (<12continuous months of amenorrhea with no identified cause other than menopause), andhas not undergone surgical sterilization (removal of ovaries and/or uterus).Examples of contraceptive methods with a failure rate of <1% per year includebilateral tubal ligation, male sterilization, hormonal contraceptive that inhibitovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.The reliability of sexual abstinence should be evaluated in relation to the durationof the clinical trial and the preferred and usual lifestyle of the patient. Periodabstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) andwithdrawal are not acceptable methods of contraception

Focal Chondral Defect Subjects

Inclusion Criteria:

1. Male or female 18-60 year of age

2. Knee pain and/or effusion

3. Inability to continue or difficulty in participation in recreational or professionalsport

4. MRI with Outerbridge Grade 4 focal chondral defect

5. Subjects must have the ability to understand and the willingness to sign a writteninformed consent document

6. For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use a contraceptive method with a failure rate of <1%per year during the treatment period. A woman is considered to be of childbearingpotential if she is postmenarcheal, has not reached a postmenopausal state (<12continuous months of amenorrhea with no identified cause other than menopause), andhas not undergone surgical sterilization (removal of ovaries and/or uterus).Examples of contraceptive methods with a failure rate of <1% per year includebilateral tubal ligation, male sterilization, hormonal contraceptive that inhibitovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.The reliability of sexual abstinence should be evaluated in relation to the durationof the clinical trial and the preferred and usual lifestyle of the patient. Periodabstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) andwithdrawal are not acceptable methods of contraception.

Exclusion Criteria:

1. Radiographic findings consistent with Kellgren-Lawrence Stage 4 disease

2. Focal chondral defect

3. Major axial deviation (>5 degrees varus or valgus)

4. Concomitant ligamentous or meniscal injury

5. BMI > 40 as defined by NIH Clinical Guidelines Body Mass Index

6. Women who are pregnant, breastfeeding or unwilling to practice birth control duringparticipation in the study

7. Concurrent participation in another investigational trial involving systemicadministration of agents (within the previous 30 days), or have received priorintra-articular injection of any form

• Or plans to participate in any other allogeneic stem cell therapy trial during the 2-year follow-up period

8. Symptomatic active cardiac or respiratory disease that requires scheduled use ofmedication

9. Neurologic disorder including, but not limited to epilepsy, Parkinson's disease,dementia, cerebrovascular disease, tumor of the nervous system, and amyotrophiclateral sclerosis.

10. Psychiatric disorder including, but not limited to schizophrenia, bipolar disorder,personality disorder, depression, anxiety, or any other mental illness that wouldprevent the completion of the study

11. Current immunosuppression from medication or disease

12. History of systemic malignancy

13. History of infection with hepatitis B, C, or HIV

14. History of inflammatory arthropathy

15. History of prior local knee infection

16. Major surgeries, other than diagnostic surgery within 4 weeks

17. Contraindication to MRI:

• Indwelling medical devices such as pacemakers, aneurysm clips, etc.

• Indwelling metal from any other cause (trauma, etc.). To be excluded withhistory and/or radiographs, as necessary

18. Screening hematology with white blood cell count < 4.5 x 109 cells/L, hematocrit <30%, and platelets <150 x 109 platelets/L

19. Have a known history of hypersensitivity or anaphylactic reaction to Dimethylsulfoxide (DMSO)

20. Have been treated in the last 6 months before enrollment for alcohol and/or drugabuse in an inpatient substance abuse program

21. Subject unlikely to complete the study as determined by the Investigator

22. Subjects must have normal marrow function, and be clinically stable with nosignificant changes in health status within 2 weeks prior to cell collection thatthe PI/Sub-Investigator deems relevant to exclude from participation. (See below fordetails of the cell collection procedure)