Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia |
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| Institution: | 1. Service de médecine vasculaire, Pôle cardiovasculaire et métabolique, Centre hospitalo-universitaire de Toulouse, Toulouse, France;2. Université de Toulouse III, Paul Sabatier, Toulouse, France;3. CNRS, Université Toulouse III, UPS UMR5273 STROMAlab, Toulouse, France;4. EFS (Etablissement Français du Sang), STROMAlab, Toulouse, France;5. Inserm U1031 STROMAlab, Toulouse, France;6. Université Toulouse III, UPS UMR5273 STROMAlab, Toulouse, France;7. CSA21, 7 chemin des silos, Toulouse, France;8. INSERM UMRS 970, Paris Cardiovascular Research Center, Université Paris Descartes, Sorbonne Paris cité, Paris, France;9. Centre d’Investigation Clinique de Biothérapies de Toulouse, Toulouse cedex 9, France;10. Direction de la Recherche Médicale et Innovation (DRMI) du CHU de Toulouse, Toulouse cedex 9, France;11. Service de chirurgie plastique, reconstructrice et esthétique, Centre hospitalo-universitaire de Toulouse, Toulouse, France;12. Service de chirurgie cardiovasculaire, Pôle cardiovasculaire et métabolique, Centre hospitalo-universitaire de Toulouse, Toulouse, France;13. Service de chirurgie vasculaire, Pôle cardiovasculaire et métabolique, Centre hospitalo-universitaire de Toulouse, Toulouse, France;1. Department of Cardiology, Shaoxing People''s Hospital (Shaoxing Hospital of Zhejiang University), Shaoxing City, Zhejiang, PR China;2. Department of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou City, Zhejiang, PR China;3. Department of Cardiology, Zhejiang Traditional Chinese Medical Hospital, Hangzhou City, Zhejiang, PR China;1. Department of Dermatology, General Hospital of Villarrobledo, Albacete, Spain;2. Department of Dermatology, Hospital General Universitario de Albacete and Universidad de Castilla La Mancha, Albacete, Spain;3. Department of Pathology, Hospital General Universitario Reina Sofía de Murcia and Universidad de Murcia, Murcia, Spain;4. Department of Ingeniería Cartográfica, Geodesia y Fotogrametría, Universidad Politécnica de Valencia, Valencia, Spain;5. Instituto Biodonostia, Hospital Universitario Donostia, San Sebastian, Spain;6. Mediteknia Dermatology Clinic, Medical Pathology Group, University of Las Palmas de Gran Canaria, Gran Canaria, Spain;1. Institute for Regenerative Cures, University of California Davis, Sacramento, California, USA;2. Department of Cell Biology and Human Anatomy, University of California Davis, Sacramento, California, USA;1. Equipe d''Accueil 3072, Mitochondrie, Stress Oxydant et Protection Musculaire, Université de Strasbourg, Fédération de Médecine Translationelle, Institut de Physiologie, 67000, Cedex, France;2. Department of Vascular Surgery and Kidney Transplantation, University Hospital, B.P. 426, 67091, Strasbourg, France;3. Department of Biophysics and Nuclear Medicine, University Hospital, B.P. 426, 67091, Strasbourg Cedex, France;4. Department of Physiology and Functional Explorations, University Hospital, B.P. 426, 67091, Strasbourg Cedex, France;5. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR7104/INSERM U964, Collège de France, Université de Strasbourg, Illkirch Cedex, France |
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| Abstract: | Background aimsNon-revascularizable critical limb ischemia (CLI) is the most severe stage of peripheral arterial disease, with no therapeutic option. Extensive preclinical studies have demonstrated that adipose-derived stroma cell (ASC) transplantation strongly improves revascularization and tissue perfusion in ischemic limbs. This study, named ACellDREAM, is the first phase I trial to evaluate the feasibility and safety of intramuscular injections of autologous ASC in non-revascularizable CLI patients.MethodsSeven patients were consecutively enrolled, on the basis of the following criteria: (i) lower-limb rest pain or ulcer; (ii) ankle systolic oxygen pressure <50 or 70 mm Hg for non-diabetic and diabetic patients, respectively, or first-toe systolic oxygen pressure <30 mm Hg or 50 mm Hg for non-diabetic and diabetic patients, respectively; (iii) not suitable for revascularization. ASCs from abdominal fat were grown for 2 weeks and were then characterized.ResultsMore than 200 million cells were obtained, with almost total homogeneity and no karyotype abnormality. The expressions of stemness markers Oct4 and Nanog were very low, whereas expression of telomerase was undetectable in human ASCs compared with human embryonic stem cells. ASCs (108) were then intramuscularly injected into the ischemic leg of patients, with no complication, as judged by an independent committee. Trans-cutaneous oxygen pressure tended to increase in most patients. Ulcer evolution and wound healing showed improvement.ConclusionsThese data demonstrate the feasibility and safety of autologous ASC transplantation in patients with objectively proven CLI not suitable for revascularization. The improved wound healing also supports a putative functional efficiency. |
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| Keywords: | adipose tissue ASC cell therapy CLI mesenchymal stromal cells |
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