Monocentric Trial: Stem Cell Emergency Life Threatening Limbs Arteriopathy (SCELTA)

Summary

The investigators designed a randomized clinical trial (stem cell emergency life threatening arteriopathy or SCELTA) to compare the therapeutic efficacy of the auto-transplant of enriched circulating EPCs (ECEPCs) with auto-transplant of BM-MNCs. ECEPCs, obtained by immunoselection of CD14+ and CD34+ cells, or BM-MNCs, were injected intramuscularly in the affected limb of patients with critical limb ischemia (CLI).

Timeline

Start

2009-09

Primary completion

2015-05

Completion

2015-10

Publications

• Background Weitz JI, Byrne J, Clagett GP, Farkouh ME, Porter JM, Sackett DL, Strandness DE Jr, Taylor LM. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: a critical review. Circulation. 1996 Dec 1;94(11):3026-49. doi: 10.1161/01.cir.94.11.3026. No abstract available.
• Background Gregg EW, Sorlie P, Paulose-Ram R, Gu Q, Eberhardt MS, Wolz M, Burt V, Curtin L, Engelgau M, Geiss L; 1999-2000 national health and nutrition examination survey. Prevalence of lower-extremity disease in the US adult population >=40 years of age with and without diabetes: 1999-2000 national health and nutrition examination survey. Diabetes Care. 2004 Jul;27(7):1591-7. doi: 10.2337/diacare.27.7.1591.
• Background Curb JD, Masaki K, Rodriguez BL, Abbott RD, Burchfiel CM, Chen R, Petrovitch H, Sharp D, Yano K. Peripheral artery disease and cardiovascular risk factors in the elderly. The Honolulu Heart Program. Arterioscler Thromb Vasc Biol. 1996 Dec;16(12):1495-500. doi: 10.1161/01.atv.16.12.1495.
• Background Meijer WT, Grobbee DE, Hunink MG, Hofman A, Hoes AW. Determinants of peripheral arterial disease in the elderly: the Rotterdam study. Arch Intern Med. 2000 Oct 23;160(19):2934-8. doi: 10.1001/archinte.160.19.2934.
• Background Melillo E, Nuti M, Bongiorni L, Golgini E, Balbarini A. [Major and minor amputation rates and lower critical limb ischemia: the epidemiological data of western Tuscany]. Ital Heart J Suppl. 2004 Oct;5(10):794-805. Italian.
• Background Inglese L, Graziani L, Tarricone R. [Percutaneous treatment of peripheral obstructive arteriopathy: the reasons for a choice]. Ital Heart J Suppl. 2000 Sep;1(9):1138-47. Italian.
• Background Dzau VJ, Gnecchi M, Pachori AS, Morello F, Melo LG. Therapeutic potential of endothelial progenitor cells in cardiovascular diseases. Hypertension. 2005 Jul;46(1):7-18. doi: 10.1161/01.HYP.0000168923.92885.f7. Epub 2005 Jun 13.
• Background Ikenaga S, Hamano K, Nishida M, Kobayashi T, Li TS, Kobayashi S, Matsuzaki M, Zempo N, Esato K. Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model. J Surg Res. 2001 Apr;96(2):277-83. doi: 10.1006/jsre.2000.6080.
• Background Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3422-7. doi: 10.1073/pnas.97.7.3422.
• Background Iwaguro H, Yamaguchi J, Kalka C, Murasawa S, Masuda H, Hayashi S, Silver M, Li T, Isner JM, Asahara T. Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation. 2002 Feb 12;105(6):732-8. doi: 10.1161/hc0602.103673.
• Background Iba O, Matsubara H, Nozawa Y, Fujiyama S, Amano K, Mori Y, Kojima H, Iwasaka T. Angiogenesis by implantation of peripheral blood mononuclear cells and platelets into ischemic limbs. Circulation. 2002 Oct 8;106(15):2019-25. doi: 10.1161/01.cir.0000031332.45480.79.
• Background Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002 Aug 10;360(9331):427-35. doi: 10.1016/S0140-6736(02)09670-8.
• Background Masuda H, Asahara T. Post-natal endothelial progenitor cells for neovascularization in tissue regeneration. Cardiovasc Res. 2003 May 1;58(2):390-8. doi: 10.1016/s0008-6363(02)00785-x.
• Background Romagnani P, Annunziato F, Liotta F, Lazzeri E, Mazzinghi B, Frosali F, Cosmi L, Maggi L, Lasagni L, Scheffold A, Kruger M, Dimmeler S, Marra F, Gensini G, Maggi E, Romagnani S. CD14+CD34low cells with stem cell phenotypic and functional features are the major source of circulating endothelial progenitors. Circ Res. 2005 Aug 19;97(4):314-22. doi: 10.1161/01.RES.0000177670.72216.9b. Epub 2005 Jul 14.
• Background Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 2003 May 30;113(5):643-55. doi: 10.1016/s0092-8674(03)00392-1.
• Background Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003 May 30;113(5):631-42. doi: 10.1016/s0092-8674(03)00393-3.
• Background Pesce M, Scholer HR. Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells. 2001;19(4):271-8. doi: 10.1634/stemcells.19-4-271.
• Background Iwama A, Oguro H, Negishi M, Kato Y, Morita Y, Tsukui H, Ema H, Kamijo T, Katoh-Fukui Y, Koseki H, van Lohuizen M, Nakauchi H. Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity. 2004 Dec;21(6):843-51. doi: 10.1016/j.immuni.2004.11.004.
• Background Melillo E, Ferrari M, Balbarini A, Pedrinelli R. Transcutaneous gases determination in diabetic critical limb ischemia. Diabetes Care. 2005 Aug;28(8):2081-2. doi: 10.2337/diacare.28.8.2081. No abstract available.
• Background Becker F, Gabrielle F, Raoux MH, Brenot R, David M. [Value of measuring transcutaneous oxygen pressure in arterial disease of the legs]. Ann Cardiol Angeiol (Paris). 1989 Oct;38(8):465-72. French.

Drugs

Indications