Intraarterial administration of bone marrow mononuclear cells in patients with critical limb ischemia a randomized-start, placebo-controlled pilot trial (PROVASA)

Circulation: Cardiovascular Interventions

Volumn 4, Issue 1, 2011, Pages 26-37

  Walter, Dirk H ^a,b   Krankenberg, Hans ^b   Balzer, Jörn O ^a   Kalka, Christoph ^c   Baumgartner, Iris ^c   Schlüter, Michael ^b   Tonn, Torsten ^d   Seeger, Florian ^a   Dimmeler, Stefanie ^a   Lindhoff Last, Edelgard ^a   Zeiher, Andreas M ^a  

^a GOETHE UNIVERSITY   (Germany)

^b UNIVERSITY OF HAMBURG   (Germany)

^c UNIVERSITY OF BERN   (Switzerland)

^d Institute of Transfusion Medicine and Immunohematology   (Germany)

Author keywords

Angiogenesis; Peripheral vascular disease; Stem cells

Indexed keywords

PLACEBO;

ADULT; AGED; ANKLE BRACHIAL INDEX; ARTICLE; BONE MARROW CELL; CELL THERAPY; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE FREE SURVIVAL; DOUBLE BLIND PROCEDURE; FEMALE; GANGRENE; HUMAN; INDEPENDENT VARIABLE; LIMB AMPUTATION; LIMB ISCHEMIA; LIMB SALVAGE; MALE; MONONUCLEAR CELL; PHASE 2 CLINICAL TRIAL; PREDICTOR VARIABLE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; ULCER HEALING;

AGED; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INJECTIONS, INTRA-ARTERIAL; ISCHEMIA; LOWER EXTREMITY; MALE; MIDDLE AGED; PERIPHERAL ARTERIAL DISEASE; PILOT PROJECTS; STEM CELL TRANSPLANTATION; STEM CELLS; TREATMENT OUTCOME;

EID: 79954448926     PISSN: 19417640     EISSN: 19417632     Source Type: Journal    
DOI: 10.1161/CIRCINTERVENTIONS.110.958348     Document Type: Article

References (27)

1. Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic). Circulation. 2006;113:e463- e654.
2. Wolfe JH, Wyatt MG. Critical and subcritical ischaemia. Eur J Vasc Endovasc Surg. 1997;13:578 -582. (Pubitemid 27332193)
3. Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 2001;344:1608 -1621. (Pubitemid 32479915)
4. Sprengers RW, Lips DJ, Moll FL, Verhaar MC. Progenitor cell therapy in patients with critical limb ischemia without surgical options. Ann Surg. 2008;247:411- 420.
5. 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 for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet. 2002;360:427- 435.
6. Huang P, Li S, Han M, Xiao Z, Yang R, Han ZC. Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes. Diabetes Care. 2005;28:2155-2160. (Pubitemid 41242461)
7. Huang PP, Yang XF, Li SZ, Wen JC, Zhang Y, Han ZC. Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow-mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans. Thromb Haemost. 2007;98: 1335-1342. (Pubitemid 350239107)
8. Durdu S, Akar AR, Arat M, Sancak T, Eren NT, Ozyurda U. Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans. J Vasc Surg. 2006;44:732-739. (Pubitemid 44441783)
9. Van Tongeren RB, Hamming JF, Fibbe WE, Van Weel V, Frerichs SJ, Stiggelbout AM, Van Bockel JH, Lindeman JH. Intramuscular or combined intramuscular/intra-arterial administration of bone marrow mononuclear cells: a clinical trial in patients with advanced limb ischemia. J Cardiovasc Surg (Torino). 2008;49:51-58. (Pubitemid 351350807)
10. Miyamoto K, Nishigami K, Nagaya N, Akutsu K, Chiku M, Kamei M, Soma T, Miyata S, Higashi M, Tanaka R, Nakatani T, Nonogi H, Takeshita S. Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans. Circulation. 2006;114:2679 -2684. (Pubitemid 44967352)
11. Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, Sadamoto K, Yokoyama A, Yamanaka T, Onodera R, Kuroda A, Baba R, Kaneko Y, Tsukie T, Kurimoto Y, Okada Y, Kihara Y, Morioka S, Fukushima M, Asahara T. Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells. 2009;27:2857-2864.
12. Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM. Intracoronary bone marrowderived progenitor cells in acute myocardial infarction. N Engl J Med. 2006;355:1210 -1221. (Pubitemid 44427445)
13. Seeger FH, Tonn T, Krzossok N, Zeiher AM, Dimmeler S. Cell isolation procedures matter: a comparison of different isolation protocols of bone marrow mononuclear cells used for cell therapy in patients with acute myocardial infarction. Eur Heart J. 2007;28:766 -772. (Pubitemid 46439231)
14. Heeschen C, Lehmann R, Honold J, Assmus B, Aicher A, Walter DH, Martin H, Zeiher AM, Dimmeler S. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation. 2004;109:1615-1622. (Pubitemid 38451717)
15. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, Dobert N, Grunwald F, Aicher A, Urbich C, Martin H, Hoelzer D, Dimmeler S, Zeiher AM. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002;106:3009 -3017. (Pubitemid 35440281)
16. Seeger FH, Rasper T, Koyanagi M, Fox H, Zeiher AM, Dimmeler S. CXCR4 expression determines functional activity of bone marrowderived mononuclear cells for therapeutic neovascularization in acute ischemia. Arterioscler Thromb Vasc Biol. 2009;29:1802-1809.
17. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med. 2006;355:1222-1232. (Pubitemid 44427446)
18. Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, Seifried E, Schachinger V, Dimmeler S, Zeiher AM. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD Registry. Circ Res. 2007;100:1234 -1241. (Pubitemid 46684137)
19. Schachinger V, Aicher A, Dobert N, Rover R, Diener J, Fichtlscherer S, Assmus B, Seeger FH, Menzel C, Brenner W, Dimmeler S, Zeiher AM. Pilot trial on determinants of progenitor cell recruitment to the infarcted human myocardium. Circulation. 2008;118:1425-1432.
20. Matoba S, Tatsumi T, Murohara T, Imaizumi T, Katsuda Y, Ito M, Saito Y, Uemura S, Suzuki H, Fukumoto S, Yamamoto Y, Onodera R, Teramukai S, Fukushima M, Matsubara H. Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J. 2008;156:1010 -1018.
21. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, Bell K, Caporusso J, Durand-Zaleski I, Komori K, Lammer J, Liapis C, Novo S, Razavi M, Robbs J, Schaper N, Shigematsu H, Sapoval M, White C, White J, Clement D, Creager M, Jaff M, Mohler E III, Rutherford RB, Sheehan P, Sillesen H, Rosenfield K. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 2007;33(suppl 1):S1-S75. (Pubitemid 46068992)
22. Amann B, Luedemann C, Ratei R, Schmidt-Lucke JA. Autologous bone marrow cell transplantation increases leg perfusion and reduces amputations in patients with advanced critical limb ischemia due to peripheral artery disease. Cell Transplant. 2009;18:371-380.
23. Nikol S, Baumgartner I, Van Belle E, Diehm C, Visona A, Capogrossi MC, Ferreira-Maldent N, Gallino A, Wyatt MG, Wijesinghe LD, Fusari M, Stephan D, Emmerich J, Pompilio G, Vermassen F, Pham E, Grek V, Coleman M, Meyer F. Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia. Mol Ther. 2008;16:972-978. (Pubitemid 351587109)
24. Britten MB, Abomaali N, Assmus B, Lehmann R, Honold J, Schmitt J, Vogl TJ, Martin, Schachinger V, Dimmeler S, Zeiher AM. Infarct remodeling following intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast enhanced magnetic resonance imaging. Circulation. 2003;108:2212-2218. (Pubitemid 37368893)
25. Dimmeler S, Leri A. Aging and disease as modifiers of efficacy of cell therapy. Circ Res. 2008;102:1319 -1330.
26. Yoon CH, Koyanagi M, Iekushi K, Seeger F, Urbich C, Zeiher AM, Dimmeler S. Mechanism of improved cardiac function after bone marrow mononuclear cell therapy: role of cardiovascular lineage commitment. Circulation. 2010;121:2001-2011.
27. D'Agostino RB Sr. The delayed-start study design. N Engl J Med. 2009;361:1304 -1306.