Tolerance Study of Allogeneic of Adipose Tissue Derived Mesenchymal Stroma/Stem Cells (AdMSC) Transplantation in Patients With Critical Limb Ischemia.

Lower limbs arteries are a frequent localization of atheroma in elderly people (15-20% after 70 years). The most severe stage of the disease, critical limb ischemia (CLI), defined clinically by the presence of rest pain or ischemic ulcer with an ankle pressure \<50 mmHg or a toe pressure \<30 mmHg or a TcPO2 \<30 mmHg, has a dramatic prognosis at 12 months, with 30% of the patients alive with an amputation, 20% mortality and only 20% of patients with a resolved disease, independently from the treatment. The only validated treatment for this disease is revascularization by endovascular procedures or open surgery. Patients with no option or poor option (high risk) for revascularization have the worst prognosis. Regenerative medicine has been studied in this field, by the injection of bone marrow derived stem cells in the ischemic limb to improve neo-angiogenesis. Despite the encouraging first results, few studies have shown a clinical interest of this kind of approach. The products tested were heterogeneous compounds derived from the bone marrow.

Different types of stem cells have recently been studied in clinical trial on ischemic disease of the heart and muscular arteries. Adipose derived stem cell, have shown in vitro and in vivo models a stronger potential of success in recovering from ischemic disease and oxygenation of the tissues.

Scientists already shown in a phase I study, that adipose derived mesenchymal cells injected in patients with CLI and no option for revascularization, had a very good tolerance and interesting effects on skin oxygenation and healing.

In order to optimize the quality of the AdMSC, to avoid the abdominal sample under anesthesia in the already suffering patients and to have the cellular product available quickly, without waiting the 15 days of culture, researchers envisage the use of AdMSC of allogeneic origin taken from healthy donors and cryopreserved after culture. Indeed, the results of phase 1 of ACellDREAM showed that almost half of the patients suffering from IC had to be amputated during the 15 days of culture. Preliminary experiments show that the phenotypic characteristics, in vitro properties and in vivo biodistribution of these cells after freezing are unchanged.

Researchers are planning a single phase, phase I study to evaluate the tolerability of intramuscular injection of allogeneic AUC in patients with critical non-revascularizable ischemia, or with persistent ischemia despite revascularization.

The aim of this phase I is to evaluate safety of allogeneic AdMSC transplantation in patients with critical limb ischemia with poor options or no option for revascularization. Ten patients will be included and have AdMSC injection in their ischemic leg. Patients will be follow-up during six months to evaluate ulcer evolution, wound healing, pain, blood flow and immune response in blood samples.

• Evaluation of the efficacy of the treatment on critical limb ischemia. [Срок оценки: Day 30, Day 90, and Day 180]
• Evaluation of the evolution of ischemia objective parameters. [Срок оценки: Day 0, Day 30, Day 90, and Day 180]
• Evaluation of the healing. [Срок оценки: Day 30, Day 90, and Day 180]
• Evaluation of the proportion of patients who required a major amputation. [Срок оценки: Day 180]
• Evaluation of the pain Evolution [Срок оценки: Day 0, Day 7, Day 30, Day 90, and Day 180]
• Evaluation of the neovascularization on the treated leg. [Срок оценки: Day 30, Day 90, and Day 180]
• Evaluation of the proportion of patients included who had all the injections. [Срок оценки: Day 0]
• Evaluation of the evolution of the quality of life [Срок оценки: Day 0, Day 30, Day 90, and Day 180]
• Evaluation of the security. [Срок оценки: Day 0, Day 1, Day 7, Day 30, Day 90, and Day 180]
• Evaluation of the immunomodulatory activity of the injected cells. [Срок оценки: Evaluated at Day 1, Day 7, Day 30, Day 90, and Day 180]
• Evaluation of the patient's immune response against Adipose-derived mesenchymal stem cells (AdMSCs) [Срок оценки: Day 30]
• Evaluation of the evolution of the quality of life. [Срок оценки: Day 0, Day 30, Day 90, and Day 180]