Cell Sources for Cardiovascular Tissue Regeneration and Engineering

Abstract

The heart has long been regarded as a post-mitotic organ. Since many years, physicians have focused on developing strategies to restore the myocardium after ischemic damage followed by ventricular dysfunction. Restoration is generally achieved through the redirection of blood flow or by supporting contractile performance. The discovery of stem cells capable of generating angiogenic or contractile cells and structures offers new horizons to patients suffering from myocardial disease. Experimental studies indicate that the delivery or mobilization of stem and progenitor cells may improve tissue perfusion and the contractile performance of the damaged heart. Another aspect of restoration is based on cardiovascular tissue engineering and the creation of three-dimensional biological conformations to replace the artificial materials frequently used during operations, i.e., valves and grafts, or even a portion of the nonfunctional myocardial tissue. At present, the underlying intra- and intercellular molecular mechanisms controlling myocardiogenesis and cardiomyocyte replacement during regenerative processes are not very well understood. In this brief review we try to give the answers to questions on certain aspects of myocardial tissue regeneration and engineering procedures.

myocardium - tissue engineering - stem cell

References

• 1 Wu K H, Liu Y L, Zhou B, Han Z C. Cellular therapy and myocardial tissue engineering: the role of adult stem and progenitor cells.  Eur J Cardiothorac Surg. 2006;  30 770-781
• 2 Dimmeler S, Zeiher A M, Schneider M D. Unchain my heart: the scientific foundations of cardiac repair.  J Clin Invest. 2005;  115 572-583
• 3 Strauer B E, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg R V, Kögler G, Wernet P. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.  Circulation. 2002;  106 1913-1918
• 4 Dib N, Michler R E, Pagani F D, Wright S, Kereiakes D J, Lengerich R, Binkley P, Buchele D, Anand I, Swingen C, Di Carli M F, Thomas J D, Jaber W A, Opie S R, Campbell A, McCarthy P, Yeager M, Dilsizian V, Griffith B P, Korn R, Kreuger S K, Ghazoul M, MacLellan W R, Fonarow G, Eisen H J, Dinsmore J, Diethrich E. Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up.  Circulation. 2005;  20 (112) 1748-1755
• 5 Deindl E, Zaruba M M, Brunner S, Huber B, Mehl U, Assmann G, Hoefer I E, Mueller-Hoecker J, Franz W M. G‐CSF administration after myocardial infarction in mice attenuates late ischemic cardiomyopathy by enhanced arteriogenesis.  FASEB J. 2006;  20 956-958
• 6 Kissel C K, Lehmann R, Assmus B, Aicher A, Honold J, Fischer-Rasokat U, Heeschen C, Spyridopoulos I, Dimmeler S, Zeiher A M. Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure.  J Am Coll Cardiol. 2007;  19 (49) 2341-2349
• 7 Tse H F, Thambar S, Kwong Y L, Rowlings P, Bellamy G, McCrohon J, Bastian B, Chan J K, Lo G, Ho C L, Lau C P. Safety of catheter-based intramyocardial autologous bone marrow cells implantation for therapeutic angiogenesis.  Am J Cardiol. 2006;  1 (98) 60-62
• 8 Galiñanes M, Loubani M, Davies J, Chin D, Pasi J, Bell P R. Autotransplantation of unmanipulated bone marrow into scarred myocardium is safe and enhances cardiac function in humans.  Cell Transplant. 2004;  13 7-13
• 9 Theiss H D, David R, Engelmann M G, Barth A, Schotten K, Naebauer M, Reichart B, Steinbeck G, Franz W M. Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM).  Eur Heart J. 2007;  28 1258-1264
• 10 Stamm C, Kleine H D, Choi Y H, Dunkelmann S, Lauffs J A, Lorenzen B, David A, Liebold A, Nienaber C, Zurakowski D, Freund M, Steinhoff G. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies.  J Thorac Cardiovasc Surg. 2007;  133 717-725
• 11 Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Hölschermann H, Yu J, Corti R, Mathey D G, Hamm C W, Süselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher A M. REPAIR‐AMI Investigators . Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction.  N Engl J Med. 2006;  21 (355) 1210-1221
• 12 Patel A N, Geffner L, Vina R F, Saslavsky J, Urschel Jr H C, Kormos R, Benetti F. Surgical treatment for congestive heart failure with autologous adult stem cell transplantation: a prospective randomized study.  J Thorac Cardiovasc Surg. 2005;  130 1631-1638
• 13 Yerebakan C, Kaminski A, Westphal B, Liebold A, Steinhoff G. Autologous bone marrow stem cell therapy for the ischemic myocardium during coronary artery bypass grafting.  Minim Invasive Ther Allied Technol. 2008;  17 143-148
• 14 Pittenger M F, Martin B J. Mesenchymal stem cells and their potential as cardiac therapeutics.  Circ Res. 2004;  95 9-20
• 15 Stamm C, Westphal B, Kleine H D, Petzsch M, Kittner C, Klinge H, Schümichen C, Nienaber C A, Freund M, Steinhoff G. Autologous bone-marrow stem-cell transplantation for myocardial regeneration.  Lancet. 2003;  361 (4) 45-46
• 16 Wollert K C, Meyer G P, Lotz J, Ringes-Lichtenberg S, Lippolt P, Breidenbach C, Fichtner S, Korte T, Hornig B, Messinger D, Arseniev L, Hertenstein B, Ganser A, Drexler H. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial.  Lancet. 2004;  364 141-148
• 17 Engelmann M G, Theiss H D, Hennig-Theiss C, Huber A, Wintersperger B J, Werle-Ruedinger A E, Schoenberg S O, Steinbeck G, Franz W M. Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G‐CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial.  J Am Coll Cardiol. 2006;  48 1712-1721
• 18 Gordon E M, Anderson W F. Gene therapy using retroviral vectors.  Curr Opin Biotechnol. 1994;  5 611-616
• 19 Ping P, Yang Q, Hammond H K. Altered beta-adrenergic receptor signaling in heart failure, in vivo gene transfer via adeno and adeno-associated virus.  Microcirculation. 1996;  3 225-228
• 20 Malosky S, Kolansky D M. Gene therapy for ischemic heart disease.  Curr Opin Cardiol. 1996;  11 361-368
• 21 Zammaretti P, Jaconi M. Cardiac tissue engineering: regeneration of the wounded heart.  Curr Opin Biotechnol. 2004;  15 430-434
• 22 Stamm C, Steinhoff G. When less is more: go slowly when repopulating a decellularized valve in vivo!.  J Thorac Cardiovasc Surg. 2006;  132 735-737
• 23 Stamm C, Khosravi A, Grabow N, Schmohl K, Treckmann N, Drechsel A, Nan M, Schmitz K P, Haubold A, Steinhoff G. Biomatrix/polymer composite material for heart valve tissue engineering.  Ann Thorac Surg. 2004;  78 2084-2092
• 24 Grabow N, Schmohl K, Khosravi A, Philipp M, Scharfschwerdt M, Graf B, Stamm C, Haubold A, Schmitz K P, Steinhoff G. Mechanical and structural properties of a novel hybrid heart valve scaffold for tissue engineering.  Artif Organs. 2004;  28 971-979
• 25 Steinhoff G, Stock U, Karim N, Mertsching H, Timke A, Meliss R R, Pethig K, Haverich A, Bader A. Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.  Circulation. 2000;  102 (19 Suppl. 3) III50-III55
• 26 Bader A, Steinhoff G, Strobl K, Schilling T, Brandes G, Mertsching H, Tsikas D, Froelich J, Haverich A. Engineering of human vascular aortic tissue based on a xenogeneic starter matrix.  Transplantation. 2000;  70 7-14
• 27 Simon A, Wilhelmi M, Steinhoff G, Harringer W, Brücke P, Haverich A. Cardiac valve endothelial cells: relevance in the long-term function of biologic valve prostheses.  J Thorac Cardiovasc Surg. 1998;  116 609-616
• 28 Bader A, Schilling T, Teebken O E, Brandes G, Herden T, Steinhoff G, Haverich A. Tissue engineering of heart valves – human endothelial cell seeding of detergent acellularized porcine valves.  Eur J Cardiothorac Surg. 1998;  14 279-284
• 29 Yang C, Sodian R, Fu P, Lüders C, Lemke T, Du J, Hübler M, Weng Y, Meyer R, Hetzer R. In vitro fabrication of a tissue engineered human cardiovascular patch for future use in cardiovascular surgery.  Ann Thorac Surg. 2006;  81 57-63
• 30 Zimmermann W H, Didié M, Döker S, Melnychenko I, Naito H, Rogge C, Tiburcy M, Eschenhagen T. Heart muscle engineering: an update on cardiac muscle replacement therapy.  Cardiovasc Res. 2006;  71 419-429
• 31 Zimmermann W H, Melnychenko I, Wasmeier G, Didié M, Naito H, Nixdorff U, Hess A, Budinsky L, Brune K, Michaelis B, Dhein S, Schwoerer A, Ehmke H, Eschenhagen T. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.  Nat Med. 2006;  12 452-458
• 32 Eschenhagen T, Zimmermann W H. Engineering myocardial tissue.  Circ Res. 2005;  97 1220-1231
• 33 Eschenhagen T, Didié M, Münzel F, Schubert P, Schneiderbanger K, Zimmermann W H. 3D engineered heart tissue for replacement therapy.  Basic Res Cardiol. 2002;  97 (Suppl. 1) I146-I152
• 34 Steinhoff G. The regenerating heart – hope for children with congenital heart defects.  Kinderkrankenschwester. 2006;  25 47-50
• 35 Garry D J, Olson E N. A common progenitor at the heart of development.  Cell. 2006;  127 1101-1104
• 36 Kattman S J, Huber T L, Keller G M. Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages.  Dev Cell. 2006;  11 723-732
• 37 Moretti A, Caron L, Nakano A, Lam J T, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans S M, Laugwitz K L, Chien K R. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification.  Cell. 2006;  127 1151-1165
• 38 Srivastava D. Genetic regulation of cardiogenesis and congenital heart disease.  Annu Rev Pathol. 2006;  1 199-213
• 39 Kelly R G, Brown N A, Buckingham M E. The arterial pole of the mouse heart forms from Fgf10-expressing cells in pharyngeal mesoderm.  Dev Cell. 2001;  1 435-440
• 40 Cai C L, Liang X, Shi Y, Chu P H, Pfaff S L, Chen J, Evans S. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart.  Dev Cell. 2003;  5 877-889
• 41 Abu-Issa R, Waldo K, Kirby M L. Heart fields: one, two or more?.  Dev Biol. 2004;  272 281-285
• 42 Buckingham M, Meilhac S, Zaffran S. Building the mammalian heart from two sources of myocardial cells.  Nat Rev Genet. 2005;  6 826-835
• 43 Laugwitz K L, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin L Z, Cai C L, Lu M M, Reth M, Platoshyn O, Yuan J X, Evans S, Chien K R. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages.  Nature. 2005;  433 647-653
• 44 Olson E N. Gene regulatory networks in the evolution and development of the heart.  Science. 2006;  313 1922-1927
• 45 Leri A, Kajstura J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration.  Physiol Rev. 2005;  85 1373-1416
• 46 Ma N, Stamm C, Kaminski A, Li W, Kleine H D, Müller-Hilke B, Zhang L, Ladilov Y, Egger D, Steinhoff G. Human cord blood cells induce angiogenesis following myocardial infarction in NOD/SCID-mice.  Cardiovasc Res. 2005;  66 45-54
• 47 Kajstura J, Rota M, Whang B, Cascapera S, Hosoda T, Bearzi C, Nurzynska D, Kasahara H, Zias E, Bonafé M, Nadal-Ginard B, Torella D, Nascimbene A, Quaini F, Urbanek K, Leri A, Anversa P. Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion.  Circ Res. 2005;  96 127-137
• 48 Pouly J, Bruneval P, Mandet C, Proksch S, Peyrard S, Amrein C, Bousseaux V, Guillemain R, Deloche A, Fabiani J N, Menasché P. Cardiac stem cells in the real world.  J Thorac Cardiovasc Surg. 2008;  135 673-678
• 49 Balsam L B, Robbins R C. Haematopoietic stem cells and repair of the ischaemic heart.  Clin Sci (Lond). 2005;  109 483-492
• 50 Murry C E, Soonpaa M H, Reinecke H, Nakajima H, Nakajima H O, Rubart M, Pasumarthi K B, Virag J I, Bartelmez S H, Poppa V, Bradford G, Dowell J D, Williams D A, Field L J. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts.  Nature. 2004;  428 664-668
• 51 Balsam L B, Wagers A J, Christensen J L, Kofidis T, Weissman I L, Robbins R C. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium.  Nature. 2004;  428 668-673
• 52 Werner N, Wassmann S, Ahlers P, Schiegl T, Kosiol S, Link A, Walenta K, Nickenig G. Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease.  Basic Res Cardiol. 2007;  102 565-571
• 53 Werner N, Nickenig G. Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy?.  Arterioscler Thromb Vasc Biol. 2006;  26 257-266
• 54 Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance.  J Cell Mol Med. 2004;  8 498-508
• 55 Hill J M, Zalos G, Halcox J P, Schenke W H, Waclawiw M A, Quyyumi A A, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk.  N Engl J Med. 2003;  348 593-600
• 56 Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Böhm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes.  N Engl J Med. 2005;  353 999-1007
• 57 Urbich C, Heeschen C, Aicher A, Dernbach E, Zeiher A M, Dimmeler S. Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells.  Circulation. 2003;  108 2511-2516
• 58 Rangappa S, Entwistle J W, Wechsler A S, Kresh J Y. Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype.  J Thorac Cardiovasc Surg. 2003;  126 124-132
• 59 Oswald J, Boxberger S, Jørgensen B, Feldmann S, Ehninger G, Bornhäuser M, Werner C. Mesenchymal stem cells can be differentiated into endothelial cells in vitro.  Stem Cells. 2004;  22 377-384
• 60 Jiang Y, Jahagirdar B N, Reinhardt R L, Schwartz R E, Keene C D, Ortiz-Gonzalez X R, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low W C, Largaespada D A, Verfaillie C M. Pluripotency of mesenchymal stem cells derived from adult marrow.  Nature. 2002;  418 41-49
• 61 D'Ippolito G, Diabira S, Howard G A, Menei P, Roos B A, Schiller P C. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential.  J Cell Sci. 2004;  117 (Pt 14) 2971-2981
• 62 Beltrami A P, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard B, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration.  Cell. 2003;  114 763-776
• 63 Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins R W, Lecapitaine N, Cascapera S, Beltrami A P, D'Alessandro D A, Zias E, Quaini F, Urbanek K, Michler R E, Bolli R, Kajstura J, Leri A, Anversa P. Human cardiac stem cells.  Proc Natl Acad Sci USA. 2007;  104 14068-14073
• 64 Leor J, Cohen S. Myocardial tissue engineering: creating a muscle patch for a wounded heart.  Ann NY Acad Sci. 2004;  1015 312-319
• 65 Menasché P. Skeletal myoblasts as a therapeutic agent.  Prog Cardiovasc Dis. 2007;  50 7-17
• 66 Pouly J, Hagège A A, Vilquin J T, Bissery A, Rouche A, Bruneval P, Duboc D, Desnos M, Fiszman M, Fromes Y, Menasché P. Does the functional efficacy of skeletal myoblast transplantation extend to nonischemic cardiomyopathy?.  Circulation. 2004;  110 1626-1631
• 67 Roell W, Lewalter T, Sasse P, Tallini Y N, Choi B R, Breitbach M, Doran R, Becher U M, Hwang S M, Bostani T, von Maltzahn J, Hofmann A, Reining S, Eiberger B, Gabris B, Pfeifer A, Welz A, Willecke K, Salama G, Schrickel J W, Kotlikoff M I, Fleischmann B K. Engraftment of connexin 43-expressing cells prevents post-infarct arrhythmia.  Nature. 2007;  450 819-824
• 68 Taylor D A, Atkins B Z, Hungspreugs P, Jones T R, Reedy M C, Hutcheson K A, Glower D D, Kraus W E. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation.  Nat Med. 1998;  4 929-933
• 69 Rangappa S, Fen C, Lee E H, Bongso A, Sim E K. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes.  Ann Thorac Surg. 2003;  75 775-779
• 70 Planat-Benard V, Silvestre J S, Cousin B, André M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Pénicaud L, Casteilla L. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives.  Circulation. 2004;  109 656-663
• 71 Kadner A, Zund G, Maurus C, Breymann C, Yakarisik S, Kadner G, Turina M, Hoerstrup S P. Human umbilical cord cells for cardiovascular tissue engineering: a comparative study.  Eur J Cardiothorac Surg. 2004;  25 635-641
• 72 Furfaro E M, Gaballa M A. Do adult stem cells ameliorate the damaged myocardium? Human cord blood as a potential source of stem cells.  Curr Vasc Pharmacol. 2007;  5 27-44
• 73 Henning R J, Abu-Ali H, Balis J U, Morgan M B, Willing A E, Sanberg P R. Human umbilical cord blood mononuclear cells for the treatment of acute myocardial infarction.  Cell Transplant. 2004;  13 729-739
• 74 Ma N, Ladilov Y, Moebius J M, Ong L, Piechaczek C, Dávid A, Kaminski A, Choi Y H, Li W, Egger D, Stamm C, Steinhoff G. Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: bone marrow vs. cord blood-derived cells.  Cardiovasc Res. 2006;  71 158-169
• 75 Moelker A D, Baks T, Wever K M, Spitskovsky D, Wielopolski P A, van Beusekom H M, van Geuns R J, Wnendt S, Duncker D J, van der Giessen W J. Intracoronary delivery of umbilical cord blood derived unrestricted somatic stem cells is not suitable to improve LV function after myocardial infarction in swine.  J Mol Cell Cardiol. 2007;  42 735-745
• 76 Kehat I, Kenyagin-Karsenti D, Snir M, Segev H, Amit M, Gepstein A, Livne E, Binah O, Itskovitz-Eldor J, Gepstein L. Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes.  J Clin Invest. 2001;  108 407-414
• 77 Erdö F, Bührle C, Blunk J, Hoehn M, Xia Y, Fleischmann B, Föcking M, Küstermann E, Kolossov E, Hescheler J, Hossmann K A, Trapp T. Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke.  J Cereb Blood Flow Metab. 2003;  23 780-785
• 78 Kofidis T, de Bruin J L, Hoyt G, Ho Y, Tanaka M, Yamane T, Lebl D R, Swijnenburg R J, Chang C P, Quertermous T, Robbins R C. Myocardial restoration with embryonic stem cell bioartificial tissue transplantation.  J Heart Lung Transplant. 2005;  24 737-744
• 79 Guan K, Nayernia K, Maier L S, Wagner S, Dressel R, Lee J H, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G. Pluripotency of spermatogonial stem cells from adult mouse testis.  Nature. 2006;  440 1199-1203
• 80 Seandel M, James D, Shmelkov S V, Falciatori I, Kim J, Chavala S, Scherr D S, Zhang F, Torres R, Gale N W, Yancopoulos G D, Murphy A, Valenzuela D M, Hobbs R M, Pandolfi P P, Rafii S. Generation of functional multipotent adult stem cells from GPR125+ germline progenitors.  Nature. 2007;  449 346-350
• 81 Guan K, Wagner S, Unsöld B, Maier L S, Kaiser D, Hemmerlein B, Nayernia K, Engel W, Hasenfuss G. Generation of functional cardiomyocytes from adult mouse spermatogonial stem cells.  Circ Res. 2007;  100 1615-1625
• 82 Rabkin-Aikawa E, Farber M, Aikawa M, Schoen F J. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves.  J Heart Valve Dis. 2004;  13 841-847
• 83 Merryman W D, Liao J, Parekh A, Candiello J E, Lin H, Sacks M S. Differences in tissue-remodeling potential of aortic and pulmonary heart valve interstitial cells.  Tissue Eng. 2007;  13 2281-2289
• 84 Rabkin-Aikawa E, Aikawa M, Farber M, Kratz J R, Garcia-Cardena G, Kouchoukos N T, Mitchell M B, Jonas R A, Schoen F J. Clinical pulmonary autograft valves: pathologic evidence of adaptive remodeling in the aortic site.  J Thorac Cardiovasc Surg. 2004;  128 552-561
• 85 Matsubayashi K, Fedak P W, Mickle D A, Weisel R D, Ozawa T, Li R K. Improved left ventricular aneurysm repair with bioengineered vascular smooth muscle grafts.  Circulation. 2003;  108 (Suppl. 1) II219-II225
• 86 Ruhparwar A, Kofidis T, Ruebesamen N, Karck M, Haverich A, Martin U. Intra-vital fluorescence microscopy for intra-myocardial graft detection following cell transplantation.  Int J Cardiovasc Imaging. 2005;  21 569-574
• 87 Rubio D, Garcia-Castro J, Martín M C, de la Fuente R, Cigudosa J C, Lloyd A C, Bernad A. Spontaneous human adult stem cell transformation.  Cancer Res. 2005;  65 3035-3039
• 88 Kofidis T, Akhyari P, Boublik J, Theodorou P, Martin U, Ruhparwar A, Fischer S, Eschenhagen T, Kubis H P, Kraft T, Leyh R, Haverich A. In vitro engineering of heart muscle: artificial myocardial tissue.  J Thorac Cardiovasc Surg. 2002;  124 63-69
• 89 Zimmermann W H, Melnychenko I, Eschenhagen T. Engineered heart tissue for regeneration of diseased hearts.  Biomaterials. 2004;  25 1639-1647
• 90 Forbess J M, Shah A S, St Louis J D, Jaggers J J, Ungerleider R M. Cryopreserved homografts in the pulmonary position: determinants of durability.  Ann Thorac Surg. 2001;  71 54-59
• 91 Stark J, Bull C, Stajevic M, Jothi M, Elliott M, de Leval M. Fate of subpulmonary homograft conduits: determinants of late homograft failure.  J Thorac Cardiovasc Surg. 1998;  115 506-514
• 92 Marshall S E, Tweedt S M, Greene C H, Ballestas L Y, Bunning K R, Costa L E, Harrison T D, Higgins C M, Hoertz M J, Hollobaugh D A, Jaffe J S, Koenig G J, Lewbart M B, Liccini M S, Lopez C S, Lynch G S, Marshall J O, Mazzoni J A, Moeller J P, Raab D C, Reap J C, Selgrath C E, Sweitzer L M, Valentino D J, Vota S A. An alternative to synthetic aortic grafts using jejunum.  J Invest Surg. 2000;  13 333-341
• 93 Allman A J, McPherson T B, Badylak S F, Merrill L C, Kallakury B, Sheehan C, Raeder R H, Metzger D W. Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response.  Transplantation. 2001;  71 1631-1640
• 94 Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, Kikuchi A, Umezu M, Okano T. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces.  Circ Res. 2002;  90 e40
• 95 Fuchs J R, Nasseri B A, Vacanti J P, Fauza D O. Postnatal myocardial augmentation with skeletal myoblast-based fetal tissue engineering.  Surgery. 2006;  140 100-107
• 96 Siepe M, Giraud M N, Pavlovic M, Receputo C, Beyersdorf F, Menasché P, Carrel T, Tevaearai H T. Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure.  J Thorac Cardiovasc Surg. 2006;  132 124-131
• 97 Kubo Y, Sekiya S, Ohigashi M, Takenaka C, Tamura K, Nada S, Nishi T, Yamamoto A, Yamaguchi A. ABCA5 resides in lysosomes, and ABCA5 knockout mice develop lysosomal disease-like symptoms.  Mol Cell Biol. 2005;  25 4138-4149
• 98 Memon I A, Sawa Y, Fukushima N, Matsumiya G, Miyagawa S, Taketani S, Sakakida S K, Kondoh H, Aleshin A N, Shimizu T, Okano T, Matsuda H. Repair of impaired myocardium by means of implantation of engineered autologous myoblast sheets.  J Thorac Cardiovasc Surg. 2005;  130 1333-1341
• 99 Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, Ishino K, Ishida H, Shimizu T, Kangawa K, Sano S, Okano T, Kitamura S, Mori H. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction.  Nat Med. 2006;  12 459-465
• 100 Naito H, Melnychenko I, Didié M, Schneiderbanger K, Schubert P, Rosenkranz S, Eschenhagen T, Zimmermann W H. Optimizing engineered heart tissue for therapeutic applications as surrogate heart muscle.  Circulation. 2006;  114 (Suppl. 1) I72-I78
• 101 Krupnick A S, Kreisel D, Riha M, Balsara K R, Rosengard B R. Myocardial tissue engineering and regeneration as a therapeutic alternative to transplantation.  Curr Top Microbiol Immunol. 2004;  280 139-164
• 102 Zeiher A M. Successful double-blind study of post-infarction patients. Repairing the heart with bone marrow (interview by Dr. med. Jochen Aumiller).  MMW Fortschr Med. 2005;  147 (48) 13
• 103 Pompilio G, Steinhoff G, Liebold A, Pesce M, Alamanni F, Capogrossi M C, Biglioli P. Direct minimally invasive intramyocardial injection of bone marrow-derived AC133+ stem cells in patients with refractory ischemia: preliminary results.  Thorac Cardiovasc Surg. 2008;  56 (2) 71-76
• 104 Klein H M, Ghodsizad A, Marktanner R, Poll L, Voelkel T, Mohammad Hasani M R, Piechaczek C, Feifel N, Stockschlaeder M, Burchardt E R, Kar B J, Gregoric I, Gams E. Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.  Heart Surg Forum. 2007;  10 (1) E66-69