Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man?

Thilo Borchardt; Thomas Braun

doi:10.1160/TH07-02-0153

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(02): 311-318
DOI: 10.1160/TH07-02-0153

Theme Issue Article

Schattauer GmbH

Cardiovascular regeneration in non-mammalian model systems: What are the differences between newts and man?

Thilo Borchardt

¹Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany

,

Thomas Braun

¹Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany

› Author Affiliations

Abstract

Summary

The mammalian heart cannot regenerate substantial cardiac injuries, while certain non-mammalian vertebrates such as certain fish (Danio rerio) and amphibiae (Notophthalmus viridescens) are able to repair the heart without functional impairment. In mammalians, the prevailing repair process is accompanied by fibrosis and scarring, while zebrafish and newts can replace lost contractile tissue by newly formed cardiac muscle with only little or no scar formation.A better understanding of cardiac regeneration in non-mammalian vertebrates might provide new insights for the manipulation of regenerative pathways in the human heart. Here, we summarize the current knowledge in cardiac regeneration of newts and the principal differences to repair processes in mammalian hearts.

Keywords

Newt - cardiac muscle - regeneration - dedifferentiation - proliferation

Full Text

References

References
1 Laflamme MA, Murry CE. Regenerating the heart. Nat Biotechnol 2005; 23: 845-856.
2 Rubart M, Field LJ. Cardiac regeneration: repopulating the heart. Annu Rev Physiol 2006; 68: 29-49.
3 Srivastava D, Ivey KN. Potential of stem-cell-based therapies for heart disease. Nature 2006; 441: 1097-1099.
4 van Laake LW, Hassink R, Doevendans PA. et al. Heart repair and stem cells. J Physiol 2006; 577: 467-478.
5 Waltenberger J. Regenerative cardiology: there are various ways to prosper. Thromb Haemost 2005; 94: 695-696.
6 Menasche P. Stem cells for clinical use in cardiovascular medicine: current limitations and future perspectives. Thromb Haemost 2005; 94: 697-701.
7 Murry CE, Field LJ, Menasche P. Cell-based cardiac repair: reflections at the 10-year point. Circulation 2005; 112: 3174-3183.
8 Rosenzweig A. Cardiac cell therapy--mixed results from mixed cells. N Engl J Med 2006; 355: 1274-1277.
9 Alvarado AS, Tsonis PA. Bridging the regeneration gap: genetic insights from diverse animal models. Nat Rev Genet 2006; 7: 873-884.
10 Brockes JP, Kumar A. Plasticity and reprogramming of differentiated cells in amphibian regeneration. Nat Rev Mol Cell Biol 2002; 3: 566-574.
11 Poss KD, Wilson LG, Keating MT. Heart regeneration in zebrafish. Science 2002; 298: 2188-2190.
12 Raya A, Koth CM, Buscher D. et al. Activation of Notch signaling pathway precedes heart regeneration in zebrafish. Proc Natl Acad Sci USA 2003; 100 (Suppl. 01) 11889-11895.
13 Bader D, Oberpriller JO. Repair and reorganization of minced cardiac muscle in the adult newt (Notophthalmus viridescens). J Morphol 1978; 155: 349-357.
14 Becker RO, Chapin S, Sherry R. Regeneration of the ventricular myocardium in amphibians. Nature 1974; 248: 145-147.
15 Oberpriller JO, Oberpriller JC. Response of the adult newt ventricle to injury. J Exp Zool 1974; 187: 249-253.
16 Anversa P, Kajstura J. Ventricular myocytes are not terminally differentiated in the adult mammalian heart. Circ Res 1998; 83: 1-14.
17 Rumyantsev PP. Replicative behaviour of different types of cardiomyocytes in terms of experimental conditions, age and systematic position of animals. In: The Development and Regenerative Potential of Cardiac Muscle. London:: Harwood Academic Publishers,; 1991. p. 81-92.
18 Soonpaa MH, Field LJ. Survey of studies examining mammalian cardiomyocyte DNA synthesis. Circ Res 1998; 83: 15-26.
19 Beltrami AP, Urbanek K, Kajstura J. et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001; 344: 1750-1757.
20 Brodsky WY, Tsirekidze NN, Arefyeva AM. Mitotic- cyclic and cycle-independent growth of cardiomyocytes. J Mol Cell Cardiol 1985; 17: 445-455.
21 Pasumarthi KB, Field LJ. Cardiomyocyte cell cycle regulation. Circ Res 2002; 90: 1044-1054.
22 Rumyantsev PP. Interrelations of the proliferation and differentiation processes during cardiact myogenesis and regeneration. Int Rev Cytol 1977; 51: 186-273.
23 Koh GY, Soonpaa MH, Klug MG. et al. Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. J Clin Invest 1995; 96: 2034-2042.
24 Soonpaa MH, Koh GY, Klug MG. et al. Formation of nascent intercalated disks between grafted fetal cardiomyocytes and host myocardium. Science 1994; 264: 98-101.
25 Rubart M, Pasumarthi KB, Nakajima H. et al. Physiological coupling of donor and host cardiomyocytes after cellular transplantation. Circ Res 2003; 92: 1217-1224.
26 Dowell JD, Rubart M, Pasumarthi KB. et al. Myocyte and myogenic stem cell transplantation in the heart. Cardiovasc Res 2003; 58: 336-350.
27 Engel FB, Hsieh PC, Lee RT. et al. FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. Proc Natl Acad Sci USA 2006; 103: 15546-15551.
28 Ebelt H, Jungblut M, Zhang Y. et al. Cellular cardiomyoplasty: improvement of left ventricular function correlates with the release of cardioactive cytokines. Stem Cells 2007; 25: 236-244.
29 Li RK, Jia ZQ, Weisel RD. et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 1996; 62: 654-660 discussion 660–651.
30 Anversa P, Leri A, Kajstura J. Cardiac regeneration. J Am Coll Cardiol 2006; 47: 1769-1776.
31 Bayes-Genis A, Roura S, Prat-Vidal C. et al. Chimerism and microchimerism of the human heart: evidence for cardiac regeneration. Nat Clin Pract Cardiovasc Med 2007; 4 (Suppl. 01) S40-S45.
32 Bayes-Genis A, Salido M, Sole Ristol F. et al. Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts. Cardiovasc Res 2002; 56: 404-410.
33 Glaser R, Lu MM, Narula N. et al. Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts. Circulation 2002; 106: 17-19.
34 Laflamme MA, Myerson D, Saffitz JE. et al. Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ Res 2002; 90: 634-640.
35 Muller P, Pfeiffer P, Koglin J. et al. Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation 2002; 106: 31-35.
36 Quaini F, Urbanek K, Beltrami AP. et al. Chimerism of the transplanted heart. N Engl J Med 2002; 346: 5-15.
37 Ince H, Petzsch M, Kleine HD. et al. Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony- stimulating factor (FIRSTLINE-AMI). Circulation 2005; 112: 3097-3106.
38 Kuethe F, Krack A, Fritzenwanger M. et al. Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion. Pharmazie 2006; 61: 957-961.
39 Valgimigli M, Rigolin GM, Cittanti C. et al. Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile. Eur Heart J 2005; 26: 1838-1845.
40 Wang Y, Tagil K, Ripa RS. et al. Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease. Int J Cardiol 2005; 100: 477-483.
41 Zohlnhofer D, Ott I, Mehilli J. et al. Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: a randomized controlled trial. J Am Med Assoc 2006; 295: 1003-1010.
42 Orlic D, Kajstura J, Chimenti S. et al. Bone marrow cells regenerate infarcted myocardium. Nature 2001; 410: 701-705.
43 Balsam LB, Wagers AJ, Christensen JL. et al. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004; 428: 668-673.
44 Deten A, Volz HC, Clamors S. et al. Hematopoietic stem cells do not repair the infarcted mouse heart. Cardiovasc Res 2005; 65: 52-63.
45 Murry CE, Soonpaa MH, Reinecke H. et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature 2004; 428: 664-668.
46 Janssens S, Dubois C, Bogaert J. et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet 2006; 367: 113-121.
47 Lunde K, Solheim S, Aakhus S. et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355: 1199-1209.
48 Schachinger V, Erbs S, Elsasser A. et al. Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIRAMI trial. Eur Heart J 2006; 27: 2775-2783.
49 Meyer GP, Wollert KC, Lotz J. et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial. Circulation 2006; 113: 1287-1294.
50 Kinnaird T, Stabile E, Burnett MS. et al. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109: 1543-1549.
51 Mangi AA, Noiseux N, Kong D. et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 2003; 9: 1195-1201.
52 Shake JG, Gruber PJ, Baumgartner WA. et al. Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 2002; 73: 1919-1925 discussion 1926.
53 Toma C, Pittenger MF, Cahill KS. et al. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002; 105: 93-98.
54 Gnecchi M, He H, Liang OD. et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 2005; 11: 367-368.
55 Silva Jr., WA, Covas DT, Panepucci RA. et al. The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells 2003; 21: 661-669.
56 Bock-Marquette I, Saxena A, White MD. et al. Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature 2004; 432: 466-472.
57 Smart N, Risebro CA, Melville AA. et al. Thymosin beta4 induces adult epicardial progenitor mobilization and neovascularization. Nature 2007; 445: 177-182.
58 Beltrami AP, Barlucchi L, Torella D. et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 2003; 114: 763-776.
59 Dawn B, Stein AB, Urbanek K. et al. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A 2005; 102: 3766-3771.
60 Oh H, Bradfute SB, Gallardo TD. et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc Natl Acad Sci USA 2003; 100: 12313-12318.
61 Oh H, Chi X, Bradfute SB. et al. Cardiac muscle plasticity in adult and embryo by heart-derived progenitor cells. Ann NY Acad Sci 2004; 1015: 182-189.
62 Hierlihy AM, Seale P, Lobe CG. et al. The postnatal heart contains a myocardial stem cell population. FEBS Lett 2002; 530: 239-243.
63 Martin CM, Meeson AP, Robertson SM. et al. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Dev Biol 2004; 265: 262-275.
64 Laugwitz KL, Moretti A, Lam J. et al. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 2005; 433: 647-653.
65 Moretti A, Caron L, Nakano A. et al. Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell 2006; 127: 1151-1165.
66 Li F, Wang X, Capasso JM. et al. Rapid transition of cardiac myocytes from hyperplasia to hypertrophy during postnatal development. J Mol Cell Cardiol 1996; 28: 1737-1746.
67 Bader D, Oberpriller J. Autoradiographic and electron microscopic studies of minced cardiac muscle regeneration in the adult newt, notophthalmus viridescens. J Exp Zool 1979; 208: 177-193.
68 Laube F, Heister M, Scholz C. et al. Re-programming of newt cardiomyocytes is induced by tissue regeneration. J Cell Sci 2006; 119: 4719-4729.
69 Oberpriller JO, Oberpriller JC, Arefyeva AM. et al. Nuclear characteristics of cardiac myocytes following the proliferative response to mincing of the myocardium in the adult newt, Notophthalmus viridescens. Cell Tissue Res 1988; 253: 619-624.
70 McDonnell TJ, Oberpriller JO. The atrial proliferative response following partial ventricular amputation in the heart of the adult newt. A light and electron microscopic autoradiographic study. Tissue Cell 1983; 15: 351-363.
71 McDonnell TJ, Oberpriller JO. The response of the atrium to direct mechanical wounding in the adult heart of the newt, Notophthalmus viridescens. An electronmicroscopic and autoradiographic study. Cell Tissue Res 1984; 235: 583-592.
72 Lien CL, Schebesta M, Makino S. et al. Gene expression analysis of zebrafish heart regeneration. PLoS Biol 2006; 4: e260.
73 Nag AC, Cheng M, Healy CJ. Studies of adult amphibian heart cells in vitro: DNA synthesis and mitosis. Tissue Cell 1980; 12: 125-139.
74 Nag AC, Healy CJ, Cheng M. DNA synthesis and mitosis in adult amphibian cardiac muscle cells in vitro. Science 1979; 205: 1281-1282.
75 Tate JM, Oberpriller JO, Oberpriller JC. Analysis of DNA synthesis in cell cultures of the adult newt cardiac myocyte. Tissue Cell 1989; 21: 335-342.
76 Matz DG, Oberpriller JO, Oberpriller JC. Comparison of mitosis in binucleated and mononucleated newt cardiac myocytes. Anat Rec 1998; 251: 245-255.
77 Soonpaa MH, Oberpriller JO, Oberpriller JC. Factors altering DNA synthesis in the cardiac myocyte of the adult newt, Notophthalmus viridescens. Cell Tissue Res 1994; 275: 377-382.
78 Bettencourt-Dias M, Mittnacht S, Brockes JP. Heterogeneous proliferative potential in regenerative adult newt cardiomyocytes. J Cell Sci 2003; 116: 4001-4009.
79 Tanaka EM, Gann AA, Gates PB. et al. Newt myotubes reenter the cell cycle by phosphorylation of the retinoblastoma protein. J Cell Biol 1997; 136: 155-165.
80 Raya A, Consiglio A, Kawakami Y. et al. The zebrafish as a model of heart regeneration. Cloning Stem Cells 2004; 6: 345-351.
81 Tate JM, Oberpriller JO. Primary cell culture and morphological characterization of ventricular myocytes from the adult newt, Notophthalmus viridescens. Anat Rec 1989; 224: 29-42.
82 Lepilina A, Coon AN, Kikuchi K. et al. A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell 2006; 127: 607-619.
83 Huang CJ, Tu CT, Hsiao CD. et al. Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish. Dev Dyn 2003; 228: 30-40.
84 Dettman RW, Denetclaw Jr., W, Ordahl CP. et al. Common epicardial origin of coronary vascular smooth muscle, perivascular fibroblasts, and intermyocardial fibroblasts in the avian heart. Dev Biol 1998; 193: 169-181.
85 Olivey HE, Compton LA, Barnett JV. Coronary vessel development: the epicardium delivers. Trends Cardiovasc Med 2004; 14: 247-251.
86 Tsonis PA. Regeneration in vertebrates. Dev Biol 2000; 221: 273-284.
87 Tanaka EM, Brockes JP. A target of thrombin activation promotes cell cycle re-entry by urodele muscle cells. Wound Repair Regen 1998; 6: 371-381.
88 Tanaka EM, Drechsel DN, Brockes JP. Thrombin regulates S-phase re-entry by cultured newt myotubes. Curr Biol 1999; 9: 792-799.
89 Simon HG, Nelson C, Goff D. et al. Differential expression of myogenic regulatory genes and Msx-1 during dedifferentiation and redifferentiation of regenerating amphibian limbs. Dev Dyn 1995; 202: 1-12.
90 Vinarsky V, Atkinson DL, Stevenson TJ. et al. Normal newt limb regeneration requires matrix metalloproteinase function. Dev Biol 2005; 279: 86-98.
91 Satoh A, Ide H, Tamura K. Muscle formation in regenerating Xenopus froglet limb. Dev Dyn 2005; 233: 337-346.
92 Kimura Y, Madhavan M, Call MK. et al. Expression of complement 3 and complement 5 in newt limb and lens regeneration. J Immunol 2003; 170: 2331-2339.
93 McGann CJ, Odelberg SJ, Keating MT. Mammalian myotube dedifferentiation induced by newt regeneration extract. Proc Natl Acad Sci USA 2001; 98: 13699-13704.
94 Amsterdam A, Hopkins N. Mutagenesis strategies in zebrafish for identifying genes involved in development and disease. Trends Genet 2006; 22: 473-478.
95 Lieschke GJ, Currie PD. Animal models of human disease: zebrafish swim into view. Nat Rev Genet 2007; 8: 353-367.
96 Udvadia AJ, Linney E. Windows into development: historic, current, and future perspectives on transgenic zebrafish. Dev Biol 2003; 256: 1-17.
97 Huang CJ, Jou TS, Ho YL. et al. Conditional expression of a myocardium-specific transgene in zebrafish transgenic lines. Dev Dyn 2005; 233: 1294-1303.
98 Curado S, Anderson RM, Jungblut B. et al. Conditional targeted cell ablation in zebrafish: a new tool for regeneration studies. Dev Dyn 2007; 236: 1025-1035.
99 Sobkow L, Epperlein HH, Herklotz S. et al. A germline GFP transgenic axolotl and its use to track cell fate: dual origin of the fin mesenchyme during development and the fate of blood cells during regeneration. Dev Biol 2006; 290: 386-397.
100 Ueda Y, Kondoh H, Mizuno N. Generation of transgenic newt Cynops pyrrhogaster for regeneration study. Genesis 2005; 41: 87-98.
101 Schnapp E, Tanaka EM. Quantitative evaluation of morpholino-mediated protein knockdown of GFP, MSX1, and PAX7 during tail regeneration in Ambystoma mexicanum . Dev Dyn 2005; 232: 162-170.
102 Echeverri K, Clarke JD, Tanaka EM. In vivo imaging indicates muscle fiber dedifferentiation is a major contributor to the regenerating tail blastema. Dev Biol 2001; 236: 151-164.
103 Echeverri K, Tanaka EM. Ectoderm to mesoderm lineage switching during axolotl tail regeneration. Science 2002; 298: 1993-1996.
104 Morrison JI, Loof S, He P. et al. Targeted gene delivery to differentiated skeletal muscle: a tool to study dedifferentiation. Dev Dyn 2007; 236: 481-488.
105 Habermann B, Bebin AG, Herklotz S. et al. An Ambystoma mexicanum EST sequencing project: analysis of 17,352 expressed sequence tags from embryonic and regenerating blastema cDNA libraries. Genome Biol 2004; 5: R67.
106 Putta S, Smith JJ, Walker JA. et al. From biomedicine to natural history research: EST resources for ambystomatid salamanders. BMC Genomics 2004; 5: 54.