Stem cell-based therapy is emerging as a novel approach for myocardial repair over conventional cardiovascular therapies. In addition to embryonic stem cells and adult stem cells from noncardiac sources, there is a small population of resident stem cells in the heart from which new cardiac cells (myocytes, vascular endothelial cells and smooth muscle cells) can be derived and used for cardiac repair in case of heart injury. It has been proposed that the clinical benefit of stem cells may arise from secreted proteins that mediate regeneration in a paracrine/autocrine manner. To be able to track the regulatory pathway on a molecular basis, utilization of proteomics in stem cell research is essential. Proteomics offers a tool that can address questions regarding stem cell response to disease/injury.

Institute of Analytical Chemistry of the ASCR v v i Veveri 97 602 00 Brno Czech Republic

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Odorico JS, Kaufman DS, Thomson JA. Multilineage differentiation from human embryonic stem cell line. Stem Cells. 2001;19:193–204. PubMed

Yamada S, Nelson TJ, Crespo-Diaz RJ, Perez-Terzic C, Liu X, Miki T, Seino S, Behfar A, Terzic A. Embryonic stem cell therapy of heart failure in genetic cardiomyopathy. Stem Cells. 2008;26:2644–2653. PubMed PMC

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. PubMed PMC

Zhang F, Pasumarthi KB. Embryonic stem cell transplantation: promise and progress an the treatment of heart disease. BioDrugs. 2008;22:361–374. PubMed

Yamanaka S, Li J, Kania G, Elliott S, Wersto RP, Van Eyk JE, Wobus AM, Boheler KR. Pluripotency of embryonic stem cells. Cell Tissue Res. 2008;331:5–22. PubMed

Tarasov KV, Tarasova YS, Tam WL, Riordon DR, Elliott ST, Kania G, Li J, Yamanaka S, Crider DG, Testa G, Li RA, Lim B, Stewart CL, Liu Y, Van Eyk JE, Wersto RP, Wobus AM, Boheler KR. B-MYB is essential for normal cell cycle progression and chromosomal stability of embryonic stem cells. PloS ONE. 2008;3:e2478. PubMed PMC

Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signalling and therapy. Circ. Res. 2008;103:1204–1219. PubMed PMC

Burchfield JS, Dimmeler S. Role of paracrine factors in stem and progenitor cell mediated cardiac repair and tissue fibrosis. Fibrogenesis Tissue Repair. 2008;1:4. PubMed PMC

Cogle CR, Yachnis AT, Laywell ED, Zander DS, Wingard JR, Steindler DA, Scott EW. Bone marrow transdifferentiation in brain after transplantation: a retrospective study. Lancet. 2004;363:1432–1437. PubMed

Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 2001;107:1395–1402. PubMed PMC

Pierret C, Spears K, Maruniak JA, Kirk MD. Neural crest as the source of adult stem cells. Stem Cells Dev. 2006;15:286–291. PubMed PMC

Popp FC, Piso P, Schlitt HJ, Dahlke MH. Therapeutic potential of bone marrow stem cells for liver diseases. Curr. Stem Cell Res. Ther. 2006;1:411–418. PubMed

Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410:701–705. PubMed

Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 2002;297:2256–2259. PubMed

Murry CE, Soonpaa MH, Reinecke H, Nakajima H, Nakajima HO, Rubart M, Pasumarthi KB, Virag JI, Bartelmez SH, Poppa V, Bradford G, Dowell JD, Williams DA, Field LJ. Haemopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature. 2004;428:664–668. PubMed

Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haemopoietic fates in ischaemic myocardium. Nature. 2004;428:668–673. PubMed

Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc. Natl. Acad. Sci. USA. 2001;98:10344–10349. PubMed PMC

van der Bogt KE, Sheikh AY, Schrepfer S, Hoyt G, Cao F, Ransohoff KJ, Swijnenburg JR, Pearl J, Lee A, Fischbein M, Contag CH, Robbins RC, Wu JC. Comparison of different adult stem cell types for treatment of myocardial ischemia. Circulation. 2008;118:S121–S129. PubMed PMC

Yeh ETH, Zhang S, Wu HD, Körbling M, Willerson JT, Estrov Z. Transdifferentiation of human peripheral blood CD34+-enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation. 2003;108:2070–2073. PubMed

Badorff C, Brandes RP, Popp R, Rupp S, Urbich C, Aicher A, Fleming I, Busse R, Zeiher AM, Dimmeler S. Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation. 2003;107:1024–1032. PubMed

Simper D, Stalboerger PG, Panetta CJ, Wang S, Caplice NM. Smooth muscle progenitor cells in human blood. Circulation. 2002;106:1199–1204. PubMed

Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105:93–98. PubMed

Wang J, Fan Y, Li C, He H, Sun Y, Lv B. Human bone marrow-derived mesenchymal stem cells transplanted into damaged rabbit heart to improve heart function. J. Zhejiang Univ. Sci. 2005;6B:242–248. PubMed PMC

Bartunek J, Croissant JD, Wijns W, Gofflot S, de Lavareille A, Vanderheyden M, Kaluzhny Y, Mazouz N, Willemsen P, Penicka M, Mathieu M, Homsy C, De Bruyne B, McEntee K, Lee IW, Heyndrickx GR. Pretreatment of adult bone marrow mesenchymal stem cells with cardiomyogenic growth factors and repair of the chronically infarcted myocardium. Am. J. Physiol. Heart Circ. Physiol. 2007;292:H1095–H1104. PubMed

Wolf D, Reinhard A, Seckinger A, Gross L, Katus HA, Hansen A. Regenerative capacity of intravenous autologous, allogeneic and human mesenchymal stem cells in the infarcted pig myocardium – complicated by myocardial tumor formation. Scand. Cardiovasc. J. 2008;19:1–7. PubMed

Min JY, Sullivan MF, Yang Y, Zhang JP, Converso KL, Morgan JP, Xiao YF. Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. Ann. Thorac. Surg. 2002;74:1568–1575. PubMed

Moelker AD, Baks T, Wever KM, Spitskovsky D, Wielopolski PA, van Beusekom HM, van Geuns RJ, Wnendt S, Duncker DJ, van der Giessen WJ. 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. PubMed

Moelker AD, Baks T, van den Bos EJ, van Geuns RJ, de Feyter PJ, Duncker DJ, van der Giessen WJ. Reduction in infarct size, but no functional improvement after bone marrow cell administration in a porcine model of reperfused myocardial infarction. Eur. Heart J. 2006;27:3057–3064. PubMed

Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J. Clin. Invest. 2005;115:572–583. PubMed PMC

Bartunek J, Vanderheyden M, Wijns W, Timmermans F, Vandekerkhove B, Villa A, Sánchez PL, Arnold R, San Román JA, Heyndrickx G, Fernandez-Aviles F. Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under scrutiny? Nat. Clin. Pract. Cardiovasc. Med. 2007;4(Suppl. 1):S100–S105. PubMed

Abdel-Latif A, Bolli R, Tleyjeh IM, Montori VM, Perin EC, Hornung CA, Zuba-Surma EK, Al-Mallah M, Dawn B. Adult bone marrow-derived cells for cardiac repair: a systematic review and meta-analysis. Arch. Intern. Med. 2007;167:989–997. PubMed

Rosenzweig A. Cardiac cell therapy – mixed results from mixed cells. New Engl. J. Med. 2006;355:1274–1277. PubMed

Lipinski MJ, Biondi-Zoccai GG, Abbate A. Impact of intracoronary cell therapy on left ventricular function in the setting af acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J. Am. Coll. Cardiol. 2007;50:1761–1767. PubMed

Smith RR, Barile L, Messina E, Marban E. Stem cells in the heart: what's the buzz all about? Part 2: Arrhythmic risks and clinical studies. Heart Rhythm. 2008;5:880–887. PubMed PMC

Kocher AA, Schlechta B, Gasparovicova A, Wolner E, Bonaros N, Laufer G. Stem cells and cardiac regeneration. Transpl. Int. 2007;20:731–746. PubMed

Segers VF, Lee RT. Stem-cell therapy for cardiac disease. Nature. 2008;451:937–942. PubMed

Mathur A, Martin JF. Stem cells and repair of the heart. Lancet. 2004;364:183–192. PubMed

Van Laake LW, Van Hoof D, Mummery CL. Cardiomyocytes derived from stem cells. Ann. Med. 2005;37:499–512. PubMed

Dawn B, Boli R. Adult bone marrow-derived cells: regenerative potential, plasticity, and tissue commitment. Basic Res. Cardiol. 2005;100:494–503. PubMed PMC

Orlic D. The strength of plasticity: stem cells for cardiac repair. Int. J. Cardiol. 2004;95(Suppl. 1):S16–S19. PubMed

Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, Garry DJ, Entman ML, Schneider MD. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. USA. 2003;100:12313–12318. PubMed PMC

Reinecke H, Minami E, Poppa V, Murry CE. Evidence for fusion between cardiac and skeletal muscle cells. Circ. Res. 2004;94:e56–e60. PubMed

Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A. Fusion of bone marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature. 2003;425:968–972. PubMed

Leri A, Kajstura J, Nadal-Ginard B, Anversa P. Some like it plastic. Circ. Res. 2004;94:132–134. PubMed

Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in adult mammalian heart. Circ. Res. 1998;83:1–14. PubMed

Schuh A, Breuer S, Al Dashti R, Sulemanjee N, Hanrath P, Weber C, Uretsky BF, Schwarz ER. Administration of vascular endothelial growth factor adjunctive to fetal cardiomyocyte transplantation and improvement of cardiac function in the rat model. J. Cardiovasc. Pharmacol. Ther. 2005;10:55–66. PubMed

Barile L, Messina E, Giacomello A, Marban E. Endogenous cardiac stem cells. Prog. Cardiovasc. Diseases. 2007;50:31–48. PubMed

Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal-Ginard V, Anversa P. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2007;114:763–776. PubMed

Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A, Kajstura J, Quaini E, Anversa P. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc. Natl. Acad. Sci. USA. 2003;100:10440–10445. PubMed PMC

Linzbach AJ. Heart failure from the point of view of quantitative anatomy. Am. J. Cardiol. 1960;5:370–382. PubMed

Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MVG, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res. 2004;95:911–921. PubMed

Linke A, Muller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Bohm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P. Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. PNAS. 2005;102:8966–8971. PubMed PMC

Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Giacomello A, Abraham MR, Marban E. Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimen. Circulation. 2007;115:896–908. PubMed

Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, Lecapitaine N, Cascapera S, Beltrami AP, D'Alessandro DA, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P. Human cardiac stem cells. PNAS. 2007;104:14068–14073. PubMed PMC

van Vliet P, Roccio M, Smits AM, van Oorschot AA, Metz CH, van Veen TA, Sluijter JP, Doevendans PA, Goumans MJ. Progenitor cells isolated from the human heart: a potential cell source for regenerative therapy. Neth. Heart J. 2008;16:163–169. PubMed PMC

Tillmanns J, Rota M, Hosoda T, Misao Y, Esposito G, Gonzalez A, Vitale S, Parolin C, Yasuzawa-Amano S, Muraski J, De Angelis A, Lecapitaine N, Siggins RW, Loredo M, Bearzi C, Bolli R, Urbanek K, Leri A, Kajstura J, Anversa P. Formation of large coronary arteries by cardiac progenitor cells. Proc. Natl. Acad. Sci. USA. 2008;105:1668–1673. PubMed PMC

Bengel FM, Schachinger V, Dimmeler S. Cell-based therapies and imaging in cardiology. Eur. J. Nucl. Med. Mol. Imaging. 2005;32:S404–S416. PubMed

Bendall SC, Hughes C, Campbell JL, Stewart MH, Pittock P, Liu S, Bonneil E, Thibault P, Bhatia M, Lajoie GA. An enhanced mass spectrometry approach reveals human embryonic stem cell growth factors in culture. Mol. Cell Proteomics. 2008;20 [epub ahead of print] PubMed PMC

Sidibe A, Yin X, Tarelli E, Xiao Q, Zampetaki A, Xu Q, Mayr M. Integrated membrane protein analysis of mature and embryonic stem cell-derived smooth muscle cells using a novel combination of CyDye/biotin labeling. Mol. Cell Proteomics. 2007;6:1788–1797. PubMed

Mayr M, Madhu B, Xu Q. Proteomics and metabolomics combined in cardiovascular research. Trends Cardiovasc. Med. 2007;17:43–48. PubMed

Choi M, An YJ, Kim SH, Roh SH, Ju HK, Hong SS, Park JH, Cho KJ, Choi DW, Kwon SW. Mass spectrometry based proteomic analysis of human stem cells: a brief review. Exp. Mol. Med. 2007;39:690–695. PubMed

Van Hoof D, Heck AJR, Krijgsveld J, Mummery CL. Proteomics and human embryonic stem cells. Stem Cell Res. 2008;1:169–182. PubMed

Ahn S, Goode RJA, Simpson RJ. Stem cell markers: insights from membrane proteomics? Proteomics. 2008;8:4946–4957. PubMed

Roche S, Provansal M, Tiers L, Jorgensen C, Lehmann S. Proteomics of primary mesenchymal stem cells. Regen. Med. 2006;1:511–517. PubMed

Maurer MH, Feldmann RE, Futterer CD, Kuschinsky W. The proteome of neural stem cells from adult rat hippocampus. Proteome Sci. 2003;1 PubMed PMC

Hoffrogge R, Mikkat S, Scharf C, Beyer S, Christoph H, Pahnke J, Mix E, Berth M, Uhrmacher A, Zubrzycki IZ, Miljan E, Völker U, Rolfs A. 2-DE proteome analysis of a proliferating and differentiating human neuronal stem cell line (ReNcell VM). Proteomics. 2006;6:1833–1847. PubMed

Elliott ST, Crider DG, Garnham CP, Boheler KR, Van Eyk JE. Two-dimensional gel electrophoresis database of murine R1 embryonic stem cells. Proteomics. 2004;4:3813–3832. PubMed

Graumann J, Hubner NC, Kim JB, Ko K, Moser M, Kumar C, Cox J, Schöler H, Mann M. Stable isotope labeling by amino acids in cell culture (SILAC) and proteome quantitation of mouse embryonic stem cells to a depth of 5, 111 proteins. Mol. Cell Proteomics. 2008;7:672–683. PubMed

Baharvand H, Hajheidari M, Zonouzi R, Ashtiani SK, Hosseinkhani S, Salekdeh GH. Comparative proteomic analysis of mouse embryonic stem cells and neonatal-derived cardiomyocytes. Biochem. Biophys. Res. Commun. 2006;349:1041–1049. PubMed

Yin X, Mayr M, Xiao Q, Mayr U, Tarelli E, Wait R, Wang W, Xu Q. Proteomic dataset of Sca-1+ progenitor cells. Proteomics. 2005;5:4533–4545. PubMed

Mayr U, Mayr M, Yin X, Begum S, Tarelli E, Wait R, Xu Q. Proteomic dataset of mouse aortic smooth muscle cells. Proteomics. 2005;5:4546–4557. PubMed

Yin X, Mayr M, Xiao Q, Wang W, Xu Q. Proteomic analysis reveals higher demand for antioxidant protection in embryonic stem cell-derived smooth muscle cells. Proteomics. 2006;6:6437–6446. PubMed

Battersby A, Jones RD, Lilley KS, McFarlane RJ, Braig HR, Allen ND, Wakeman JA. Comparative proteomic analysis reveals differential expression of Hsp25 following the directed differentiation of mouse embryonic stem cells. Biochim. Biophys. Acta. 2007;1773:147–156. PubMed

Foster LJ, Zeemann PA, Li C, Mann M, Jensen ON, Kassem M. Differential expression profilling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation. Stem Cells. 2005;23:1367–1377. PubMed

Wallin E, von Heijne G. Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms. Protein Sci. 1998;7:1029–1038. PubMed PMC

Gundry RL, Boheler KR, Van Eyk JE, Wollscheid B. A novel role for proteomics in the discovery of cellsurface markers on stem cells: scratching the surface. Proteomics Clin. Appl. 2008;2:892–903. PubMed PMC

Jeong JA, Lee Y, Lee W, Jung S, Lee D, Jeong N, Lee HS, Bae Y, Jeon C, Kim H. Proteomic analysis of the hydrophobic fraction of mesenchymal stem cells derived from human umbilical cord blood. Mol. Cells. 2006;22:36–43. PubMed

Nunomura K, Nagano K, Itagaki C, Taoka M, Okamura N, Yamauchi Y, Sugano S, Takahashi N, Izumi T, Isobe T. Cell surface labeling and mass spectrometry reveal diversity of cell surface markers and signaling molecules expressed in undifferentiated mouse embryonic stem cells. Mol. Cell Proteomics. 2005;4:1968–1976. PubMed

Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM, Dimmeler S. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J. Mol. Cell Cardiol. 2005;39:733–742. PubMed

Pula G, Mayr U, Evans C, Prokopi M, Vara DS, Yin X, Astroulakis Z, Xiao Q, Hill J, Xu Q, Mayr M. Proteomics identifies thymidine phosphorylase as a key regulator of the angiogenic potential of colony-forming units and endothelial progenitor cell cultures. Circ. Res. 2009;104:32–40. PubMed

Arrell DK, Niederländer NJ, Faustino RS, Behfar A, Terzic A. Cardioinductive network guiding stem cell differentiation revealed by proteomic cartography of TNFα-primed endodermal secretome. Stem Cells. 2008;26:387–400. PubMed

Scobioala S, Klocke R, Kuhlmann M, Tian W, Hasib L, Milting H, Koenig S, Stelljes M, El-Banayosy A, Tenderich G, Michel G, Breithardt G, Nikol S. Up-regulation of nestin in the infarcted myocardium potentially indicates differentiation of resident cardiac stem cells into various lineages including cardiomyocytes. FASEB J. 2008;22:1021–1031. PubMed

Doyle B, Sorajja P, Hynes B, Kumar AH, Araoz PA, Stalboerger PG, Miller D, Reed C, Schmeckpeper J, Wang S, Liu C, Terzic A, Kruger D, Riederer S, Caplice NM. Progenitor cell therapy in a porcine acute myocardial infarction model induces cardiac hypertrophy, mediated by paracrine secretion of cardiotrophic factors including TGFbeta1. Stem Cells Dev. 2008;17:941–951. PubMed PMC

Takahashi M, Li TS, Suzuki R, Kobayashi T, Ito H, Ikeda Y, Matsuzaki M, Hamano K. Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. Am. J. Physiol. Heart Circ. Physiol. 2006;291:H886–H893. PubMed

Tang YL, Tang Y, Zhang YC, Qian K, Shen L, Phillips MI. Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J. Am. Coll. Cardiol. 2005;46:1339–1350. PubMed

Li W, Ma N, Ong LL, Nesselmann C, Klopsch C, Ladilov Y, Furlani D, Piechaczek C, Moebius JM, Lutzow K, Lendlein A, Stamm C, Li RK, Steinhoff G. Bcl-2 engineered MSCs inhibited apoptosis and improved heart function. Stem Cells. 2007;25:2118–2127. PubMed

Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cells-released paracrine factor mediating myocardial survival and repair. Proc. Natl. Acad. Sci. USA. 2007;104:1643–1648. PubMed PMC