Subcutaneous Injections of ASC to Heal Digital Ulcers in Patients With Scleroderma.

Inclusion Criteria:

• Male or female patient ≥18 years of age,
• Patient with systemic sclerosis according to the 2013 ACR/EULAR classificationcriteria9,
• SSc patient with at least one refractory active ischemic digital ulcer at "inclusionvisit" (see below the eligibility conditions of a DU),
• Age > 50 years and not treated with any kind of hormone replacement therapy for atleast 2 years prior to screening, with amenorrhea for at least 24 consecutive monthsprior to screening. An assessment of serum follicle stimulating hormone showing alevel of > 40 TU/L at screening may be used to exclude childbearing potential, basedon the discretion of the investigator,
• Patient must have provided written informed consent prior to enrolment,
• Patient must be able to understand their requirements of participating in theprotocol,
• Patient affiliated to a social security system.
• Relative to each DU : The DU at " inclusion visit " must show all the following characteristics:

1. Located beyond the proximal interphalangeal joint, on finger surface (includedperiungual ulcers),
2. Of ischemic origin according to the physician,
3. Not over subcutaneous calcifications or bone relief,
4. Active DU,
5. Refractory after 10±2 weeks of standard of care according to EULAR recommendations26 (that is either still active (chronic) or new occurrence despite standard of care)

Exclusion Criteria:

• Current smoker or tobacco consumption stopped for less than 3 months prior toinclusion, - Patient participating in a clinical trial or having participated in aclinical trial within the previous 3 months,
• Patients on statins, who have received treatment for less than 3 months prior toScreening or whose treatment has not been stable during this period,
• Patients on vasodilators, such as endothelin receptor antagonists (ERAs), PDE5inhibitors (e.g. sildenafil, tadalafil), calcium channel blockers, ACE-inhibitors,nitroglycerin, alpha adrenergic blockers, or angiotensin II receptor antagonists,N-acetylcysteine, antiplatelet aggregation therapy and low molecular weight heparinwho have received treatment if present for less than 3 months prior to "inclusionvisit" or whose treatment has not been stable for at least 1 month prior to "inclusionvisit",
• Treatment with disease modifying agents such as methotrexate, mycophenolate mofetil,azathioprine, tacrolimus, Interferons and cyclophosphamide, those drugs should be stopat least 1 month prior study entry.
• Treatment with oral corticosteroids (> 10 mg/day of prednisone or equivalent),
• Systemic antibiotics (oral and TV) to treat infected DU(s) within 4 weeks prior to "inclusion visit",
• Use of topical growth factors, hyperbaric oxygen,
• Local injection of botulinum toxin in an affected finger within 4 weeks prior to "inclusion visit",
• Surgical sympathectomy of the upper limbs or surgical wound debridement within 1 monthprior to "inclusion visit",
• Liposuction technically impossible,
• Patient who underwent autologous hematopoietic stem cell transplantation (HSCT) withinless than 1 year,
• Patients with an indication for intensification by autologous HSCT (according to EBMTguidelines and national RCP MATHEC),
• History of cancer in the last five years, except for successfully excised basalcell/squamous cell carcinoma, or successfully excised early melanoma of the skin.Subjects, who had successfully tumor resection or radiation or chemotherapy more than 5 years from inclusion and no recurrence, may be enrolled in the study, - Subjects whohave active proliferative retinopathy,
• Positive HIV-1 or 2, HTLV-1 or 2, HBV or HCV,
• Patients with a history of stroke, myocardial infarction or severe arrhythmia in thelast 6 months
• Patient who had severe cardiac failure in the last 6 months,
• Females who are pregnant or breastfeeding or plan to do so during the course of thisstudy,
• Patient under judicial protection, - Refusal of the patient to participate in thestudy.
• Relative to each DU:

1. Digital ulcer due to conditions other than scleroderma,
2. Non ischemic digital ulcer,
3. Ulcers with osteomyelitis, or clinically uncontrolled infection,
4. Infected digital ulcer requiring systemic antibiotherapy,
5. Digital ulcer requiring urgent surgery.