Treatment of Refractory Systemic Lupus Erythematosus by Allogeneic Mesenchymal Stem Cells Derived From the Umbilical Cord

Inclusion Criteria:

• Age > 18 years and < 70 years.
• Diagnosis of Systemic Lupus Erythematosus (SLE) according to the ACR criteria withpositive antinuclear antibodies.
• Subjects with sustained disease activity defined by a SELENA- SLEDAI SLE activityindex ≥ 6 at baseline,
• Inefficacy or adverse effects necessitating discontinuation of first and second linetherapies of SLE including: a. Prednisone orally ≥ 6 mg / day (or equivalent) for at least 28 days. b. At leastone or more of the following immunosuppressive therapies for 3 months in total: i-Cyclophosphamide, iv bolus ≥500 mg / month for 3 months minimum ii- Mycophenolatemofetil, orally or equivalent at a dose> 2000 mg / day for at least 90 days iii-Azathioprine orally at a dose> 2 mg / kg / day for at least 90 days; iv- Methotrexateorally or parenterally, at doses > 20mg / week for at least 90 days; v- Leflunomideorally, at a dose of> 10-mg / day for at least 90 days; vi- Rituximab (anti-CD20)intravenous bolus 375 mg / m2, once a week for four weeks or total dose of 1 g twice aday for two weeks vii- Cyclosporine orally, at a dose of 2.5-5 mg / kg / day, for atleast 90 days; viii- Belimumab intravenously at monthly bolus of 10 mg / kg infusion),for at least 3 months.
• Patient who received treatment of SLE at stable doses for a minimum of 30 days priorto eligibility, including one of the following treatments: prednisone (or equivalent)alone or combined with antimalarial treatment, an anti-inflammatory steroidal and / oran immunosuppressant.
• Negative pregnancy test for women of childbearing age.
• For men and women : Using effective contraceptive methods during treatment and within 3 months after the end of treatment for men with her partner of childbearing age
• Signed Informed Consent.
• Affiliation to social security.

Exclusion Criteria:

1- Pregnancy, breastfeeding or lack of appropriate contraception during study duration

• Presence of:

1. Renal failure: calculated creatinine clearance of <30 ml / min
2. Cardiac failure: clinical signs of congestive heart failure; left ventricularejection fraction <40% on echocardiography; uncontrolled ventricular arrhythmia;
3. Hepatitis defined by abnormal levels of transaminases (AST, ALT> 2 x normal) notrelated to disease activity.
4. Respiratory disease: mean PAP> 50 mmHg (echocardiography), respiratory failuredefined by a resting blood pressure of oxygen at PaO 2 < 70 mmHg and / or PaCO2 > 50 mmHg without oxygen

• Severe psychiatric disorders, including severe psychosis related to SLE, which wouldprevent to give informed consent or to undergo the procedure.
• Active neoplasia or concomitant myelodysplasia, except for basal cell carcinoma orsquamous cell carcinoma or in situ cervix carcinoma.
• Bone marrow failure defined by neutropenia <0.5.109/L, thrombocytopenia <30. 109 / L,anemia < 8 g / dL, lymphopenia CD4 + <200 x 106 / L caused by another disease thanSLE.
• Acute or chronic uncontrolled infection: HIV 1/2, HTLV-1/2, Hepatitis B (HBsAg surfaceantigen), Hepatitis C with positive PCR
• Patient having received belimumab within 2 months of belimumab within 2 months ofBaseline, or having received rituximab or other B cell depleting biologic therapywithin 6 months of Baseline
• Current substance abuse or recent (within 60 days) history of substance abuse
• Patient in periods of exclusion from the national roster of researchers
• Patient with Linguistic or psychological incapacity to sign informed consent
• Patient already included in another study at the same time.
• Poor patient compliance.
• Patient under legal protection.