Cell-Based Therapy for Myocar Ischemia and Infarction: Pathophysiological Mechanisms Supplemental Table 1 Clinical trials of cell-based cardiac repair without s or with nonrandom study design Head-tohead compariso n between and CPC 27 pts in each for left ventricular angiograph y followup 18 CPC, 19 for MRI follow-up Head-tohead compariso n between and CPC 9 BMSC, 11 CPC 20 treated, 13 s or CPC 4 days post or CPC 4 days post or CPC 5 days after 14 days post No s 5 treated 6 days after A open study, s were pts not participati ng 14 pts treated, 9 19 treated, 16 s G-CSF mobilizati on 10 µg/kg for 7 days starting 48 h after PCI CD133+ CPC 11.6 days after A echo, PET at 4 MRI at 4 MRI at 12 G-CSF s.c. MRI, angiography at 6 echo at 3 and 12 SPECT, PET at 4 LVEF for both cell types; viability LVEF for both cell types LVEF for both cell types (1) (2) (3) (4) No benefit (5) Wall motion ; perfusion ; no significant change in LVEF between s (6) (7) 1
Cell-Based Therapy for Myocar Ischemia and Infarction: Pathophysiological Mechanisms No s No s 6 patients undergoing CABG 12 pts undergoing CABG CD 133+ stem cells 10 days to 3 mts after CD 133+ stem cells 10 days to 3 mts after No s 10 BMC Transendocar No s 27 BMC Transendocar, open label, open label Single patient 14 BMC, 7 11 BMC, 9 1 Skeletal, No s 10 Skeletal No s 5 Skeletal Transendocar Transendocar Transendocar Echo, ergo at 3 Echo, ergo at 12 Echo, angiography, SPECT, ergo at 2 and 4 Echo, SPECT, ergo at 6 and 12 Echo, PET at 5 Echo at 10 Echo, angiography, and 6 Perfusion ; LVEF Perfusion ; LVEF CCS score ; treadmill exercise CCS score ; treadmill exercise LVEF for treated pts Exercise capacity and ischemia in treated pts (8) (9) (10) (11) (12) (13) EF (14) regional wall motion LVEF only in angiography, not in MRI or ; no increase in LVEF but wall motion at 6 (15) (16) 2
Cell-Based Therapy for Myocar Ischemia and Infarction: Pathophysiological Mechanisms No s 12 Skeletal No s 10 Skeletal No s 10 Skeletal Myocar injections using the transcoronar y-venous approach No s 8 Transendocar No s 24 Skeletal CABG or LVAD) Echo, PET at 3 Echo at 12 echo at 6 MRI at 3 MRI up to 6, echo up to 24 ; viability NYHA class ; LVEF unchanged; New uptake of glucose (PET) in scar tissue and histology showed survival of in 6 patients (17) (18) (19) (20) (21) 18 each Left ventricular angio, SPECT, PET at 3 No s 15 BMC Myocar injections using the transcoronar y-venous approach SPECT, angiography at 1 year LVEF in treated ; reduction in infarct size and Visually more collaterals; angina ; perfusion (22) (23) 3
Cell-Based Therapy for Myocar Ischemia and Infarction: Pathophysiological Mechanisms Healthy volunteers served as s 16 treated, 15 healthy volunteers G-CSF 10 µg/kg for 7 days MRI, stress testing at 1 and 3 No cardiac benefit BMSC, bone marrow stem cell; CPC, circulating progenitor cells;, myocar infarct; PET, positron emission tomography; SPECT, single-photon emission computed tomography; CABG, coronary atery bypass grafting; CCS, Canadian Cardiovascular Society angina score; LVAD, left ventricular assist device; NYHA, New York Heart Assocation; PCI, percutaneous coronary intervention; EF, ejection fraction. (24) Literature Cited 1. Assmus B, Schachinger V, Teupe C, Britten M, Lehmann R, et al. 2002. Transplantation of progenitor cells and regeneration enhancement in acute myocar infarction (TOPCARE- A). Circulation 106:3009--17 2. Britten MB, Abolmaali ND, Assmus B, Lehmann R, Honold J, et al. 2003. Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocar infarction (TOPCARE-A): mechanistic insights from serial contrast-enhanced magnetic resonance imaging. Circulation 108:2212--18 3. Schachinger V, Assmus B, Britten MB, Honold J, Lehmann R, et al. 2004. Transplantation of progenitor cells and regeneration enhancement in acute myocar infarction: final one-year results of the TOPCARE-A Trial. J. Am. Coll. Cardiol. 44:1690--99 4. Fernandez-Aviles F, San Roman JA, Garcia-Frade J, Fernandez ME, Penarrubia MJ, et al. 2004. Experimental and clinical regenerative capability of human bone marrow cells after myocar infarction. Circ. Res. 95:742--48 5. Kuethe F, Richartz BM, Sayer HG, Kasperb C, Wernera GS, et al. 2004. Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocar infarctions. Int. J. Cardiol. 97:123--27 6. Kuethe F, Figulla HR, Herzau M, Voth M, Fritzenwanger M, et al. 2005. Treatment with granulocyte colony-stimulating factor for mobilization of bone marrow cells in patients with acute myocar infarction. Am. Heart J. 150:115 7. Bartunek J, Vanderheyden M, Vandekerckhove B, Mansour S, De Bruyne B, et al. 2005. injection of CD133-positive enriched bone marrow progenitor cells promotes 4
Cell-Based Therapy for Myocar Ischemia and Infarction: Pathophysiological Mechanisms cardiac recovery after recent myocar infarction: feasibility and safety. Circulation 112:I178--83 8. Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, et al. 2003. Autologous bone-marrow stem-cell transplantation for myocar regeneration. Lancet 361:45--46 9. Stamm C, Kleine HD, Westphal B, Petzsch M, Kittner C, et al. 2004. CABG and bone marrow stem cell transplantation after myocar infarction. Thorac. Cardiovasc. Surg. 52:152--58 10. Fuchs S, Satler LF, Kornowski R, Okubagzi P, Weisz G, et al. 2003. Catheter-based autologous bone marrow myocar injection in no-option patients with advanced coronary artery disease: a feasibility study. J. Am. Coll. Cardiol. 41:1721--24 11. Fuchs S, Kornowski R, Weisz G, Satler LF, Smits PC, et al. 2006. Safety and feasibility of transendocar autologous bone marrow cell transplantation in patients with advanced heart disease. Am. J. Cardiol. 97:823--29 12. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, et al. 2003. Transendocar, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107:2294--302 13. Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa ALS, et al. 2004. Improved exercise capacity and ischemia 6 and 12 after transendocar injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 110: II213--18 14. Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, et al. 2001. Myoblast transplantation for heart failure. Lancet 357:279--80 15. Menasche P, Hagege AA, Vilquin JT, Desnos M, Abergel E, et al. 2003. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J. Am. Coll. Cardiol. 41:1078--83 16. Smits PC, van Geuns RJ, Poldermans D, Bountioukos M, Onderwater EE, et al. 2003. Catheter-based intramyocar injection of autologous skeletal as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J. Am. Coll. Cardiol. 42:2063--69 17. Herreros J, Prosper F, Perez A, Gavira JJ, Garcia-Velloso MJ, et al. 2003. Autologous intramyocar injection of cultured skeletal muscle-derived stem cells in patients with nonacute myocar infarction. Eur. Heart J. 24:2012--20 18. Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzezniczak J, et al. 2004. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocar injury: phase I clinical study with 12 of follow-up. Am. Heart J. 148:531--37 5
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