変形性膝関節症における間葉系幹細胞の影響

Inclusion Criteria:

Knee Osteoarthritis Subjects

1. Male or female 18-60 years of age
2. Confirmed diagnosis of knee osteoarthritis based on clinical and radiographic findings
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 written informed consent document
7. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual 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 childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (<12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Period abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal 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 professional sport
4. MRI with Outerbridge Grade 4 focal chondral defect
5. Subjects must have the ability to understand and the willingness to sign a written informed consent document
6. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual 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 childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (<12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Period abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal 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 during participation in the study

7. Concurrent participation in another investigational trial involving systemic administration of agents (within the previous 30 days), or have received prior intra-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 of medication

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

10. Psychiatric disorder including, but not limited to schizophrenia, bipolar disorder, personality disorder, depression, anxiety, or any other mental illness that would prevent 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 with history 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 Dimethyl sulfoxide (DMSO)

20. Have been treated in the last 6 months before enrollment for alcohol and/or drug abuse 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 no significant changes in health status within 2 weeks prior to cell collection that the PI/Sub-Investigator deems relevant to exclude from participation. (See below for details of the cell collection procedure)