Thymosin β4 and Cardiac Regeneration: Are We Missing a Beat?

Stem Cell Reviews and Reports

Volumn 9, Issue 3, 2013, Pages 303-312

  Gajzer, David C ^a   Balbin, Jerome ^a   Chaudhry, Hina W ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Cardiac development; Ischemic biology basic studies; Myogenesis; Progenitor cells; Stem cells

Indexed keywords

THYMOSIN; THYMOSIN BETA(4);

ARTICLE; CELL DIFFERENTIATION; CYTOLOGY; DRUG EFFECT; HEART; HEART INFARCTION; HEART MUSCLE; HEART MUSCLE CELL; HUMAN; METABOLISM; REGENERATION; STEM CELL; STEM CELL TRANSPLANTATION;

CELL DIFFERENTIATION; HEART; HUMANS; MYOCARDIAL INFARCTION; MYOCARDIUM; MYOCYTES, CARDIAC; REGENERATION; STEM CELL TRANSPLANTATION; STEM CELLS; THYMOSIN;

ANIMALIA;

EID: 84878990835     PISSN: 15508943     EISSN: 15586804     Source Type: Journal    
DOI: 10.1007/s12015-012-9378-3     Document Type: Article

References (96)

1. Hoover-Plow, J., & Gong, Y. (2012). Challenges for heart disease stem cell therapy. Vascular Health and Risk Management, 8, 99-113.
2. Leri, A., Kajstura, J., Anversa, P., & Frishman, W. H. (2008). Myocardial regeneration and stem cell repair. Current Problems in Cardiology, 33, 91-153.
3. Bicknell, K. A., Coxon, C. H., & Brooks, G. (2007). Can the myocyte's cell cycle be reprogrammed? Journal of Molecular and Cellular Cardiology, 42, 706-721.
4. Zhou, B., & Pu, W. T. (2012). Isolation and characterization of embryonic and adult epicardium and epicardium-derived cells. Methods in Molecular Biology, 843, 155-168.
5. Smart, N., Risebro, C. A., Melville, A. A., et al. (2007). Thymosin beta 4 induces adult epicardial progenitor mobilization and neovascularization. Nature, 445, 177-182.
6. Bock-Marquette, I., Saxena, A., White, M. D., DiMaio, J. M., & Srivastava, D. (2004). Thymosin β4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair. Nature, 432, 466-472.
7. Bock-Marquette, I., Shrivastava, S., Pipes, G. C., et al. (2009). Thymosin ß 4 mediated PKC activation is essential to initiate the embryonic coronary developmental program and epicardial progenitor cell activation in adult mice in vivo. Journal of Molecular and Cellular Cardiology, 46, 728-738.
8. Rubart, M., & Field, L. J. (2006). Cardiac regeneration: Repopulating the heart. Annual Review of Physiology, 68, 29-49.
9. Bergmann, O., Bhardwaj, R. D., Bernard, S., et al. (2009). Evidence for cardiomyocyte renewal in humans. Science, 324, 98-102.
10. Olivetti, G., Abbi, R., Quaini, F., et al. (1997). Apoptosis in the failing human heart. The New England Journal of Medicine, 336, 1131-1141.
11. Olivetti, G., Giordano, G., Corradi, D., et al. (1995). Gender differences and aging: Effects on the human heart. Journal of the American College of Cardiology, 26, 1068-1079.
12. Kajstura, J., Gurusamy, N., Ogórek, B., et al. (2010). Myocyte turnover in the aging human heart. Circulation Research, 107, 1374-1386.
13. Hsieh, P. C., Segers, V. F., Davis, M. E., et al. (2007). Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nature Medicine, 13, 970-974.
14. Jopling, C., Sleep, E., Raya, M., et al. (2010). Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature, 464, 606-609.
15. Nygren, J. M., Jovinge, S., Breitbach, M., et al. (2004). Bone marrow-derived hematopoietic cells generate cardiomyocytes at a low frequency through cell fusion, but not transdifferentiation. Nature Medicine, 10, 494-501.
16. Murry, C. E., Soonpaa, M. H., Reinecke, H., et al. (2004). Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature, 428, 664-668.
17. Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701-705.
18. Jackson, K. A., Majka, S. M., Wang, H., et al. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. The Journal of Clinical Investigation, 107, 1395-1402.
19. Orlic, D., Kajstura, J., Chimenti, S., et al. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings of the National Academy of Sciences of the United States of America, 98, 10344-10349.
20. Balsam, L. B., Wagers, A. J., Christensen, J. L., Kofidis, T., Weissman, I. L., & Robbins, R. C. (2004). Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature, 428, 668-673.
21. Lunde, K., Solheim, S., Aakhus, S., et al. (2005). Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects. Scandinavian Cardiovascular Journal, 39, 150-158.
22. Schachinger, V., Erbs, S., Elsässer, A., et al. (2006). Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. The New England Journal of Medicine, 355, 1210-1221.
23. Wollert, K. C., Meyer, G. P., Lotz, J., et al. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: The BOOST andomized controlled clinical trial. Lancet, 364, 141-148.
24. Mercola, M., Ruis-Lozano, P., & Schneider, M. D. (2011). Cardiac muscle regeneration: Lessons from development. Genes & Development, 25, 299-309.
25. Beltrami, A. P., Barlucchi, L., Torella, D., et al. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114, 763-776.
26. Bearzi, C., Rota, M., Hosoda, T., et al. (2007). Human cardiac stem cells. Proceedings of the National Academy of Sciences of the United States of America, 104, 14068-14073.
27. Dawn, B., Stein, A. B., Urbanek, K., et al. (2005). Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infracted myocardium, and improve cardiac function. Proceedings of the National Academy of Sciences of the United States of America, 102, 3766-3771.
28. Tang, X. L., Rokosh, G., Sanganalmath, S. K., et al. (2010). Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation, 121, 293-305.
29. Rota, M., Padin-Iruegas, M. E., Misao, Y., et al. (2008). Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circulation Research, 103, 107-116.
30. Bolli, R., Chugh, A. R., D'Amario, D., et al. (2011). Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): Initial results of a randomised phase 1 trial. Lancet, 378, 1847-1857.
31. Laugwitz, K. L., Moretti, A., Lam, J., et al. (2005). Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature, 433, 647-653.
32. Domian, I. J., Chiravuri, M., van der Meer, P., et al. (2009). Generation of functional ventricular heart muscle from mouse ventricular progenitor cells. Science, 326, 426-429.
33. Moretti, A., Caron, L., Nakano, A., et al. (2006). Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification. Cell, 127, 1151-1165.
34. Oh, H., Bradfute, S. B., Gallardo, T. D., et al. (2003). Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences of the United States of America, 100, 12313-12318.
35. Asakura, A., & Rudnicki, M. A. (2002). Side population cells from diverse adult tissues are capable of in vitro hematopoietic differentiation. Experimental Hematology, 30, 1339-1345.
36. Gussoni, E., Soneoka, Y., Strickland, C. D., et al. (1999). Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature, 401, 390-394.
37. Martin, C. M., Meeson, A. P., Robertson, S. M., et al. (2004). Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Developmental Biology, 265, 262-275.
38. Goodell, M. A., Brose, K., Paradis, G., Conner, A. S., & Mulligan, R. C. (1996). Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. The Journal of Experimental Medicine, 183, 1797-1806.
39. Zhou, S., Schuetz, J. D., Bunting, K. D., et al. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nature Medicine, 7, 1028-1034.
40. Martin, C. M., et al. (2004). Abcg2 cardiac stem cell population participates in repair of adult mouse and human heart. Supplement Circulation 110 [Abstract no. 811] abstract citation.
41. Messina, E., De Angelis, L., Frati, G., et al. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circulation Research, 95, 911-921.
42. Smith, R. R., Barile, L., Cho, H. C., et al. (2007). Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation, 115, 896-908.
43. Chimenti, I., Smith, R. R., Li, T. S., et al. (2010). Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circulation Research, 106, 971-980.
44. Tang, Y. L., Zhu, W., Cheng, M., et al. (2009). Hypoxic preconditioning enhances the benefit of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression. Circulation Research, 104, 1209-1216.
45. Takehara, N., Tsutsumi, Y., Tateishi, K., et al. (2008). Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction. Journal of the American College of Cardiology, 52, 1858-1865.
46. Makkar, R. R., Smith, R. R., Cheng, K., et al. (2012). Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): A prospective, randomised phase 1 trial. Lancet, 379, 895-904.
47. Smart, N., Bollini, S., Dubé, K. N., et al. (2011). De novo cardiomyocytes from within the activated adult heart after injury. Nature, 474, 640-644.
48. Manner, J., Perez-Pomares, J. M., Macias, D., & Munoz-Chapuli, R. (2001). The origin, formation and developmental significance of the epicardium: A review. Cells, Tissues, Organs, 169, 89-103.
49. Wessels, A., & Perez-Pomares, J. M. (2004). The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells. The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology, 276, 43-57.
50. Wilm, B., Ipenberg, A., Hastie, N. D., Burch, J. B., & Bader, D. M. (2005). The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development, 132, 5317-5328.
51. Cai, C. L., Martin, J. C., Sun, Y., et al. (2008). A myocardial lineage derives from Tbx18 epicardial cells. Nature, 454, 104-108.
52. Zhou, B., Ma, Q., Rajagopal, S., et al. (2008). Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature, 454, 109-113.
53. Red-Horse, K., Ueno, H., Weissman, I. L., & Krasnow, M. A. (2010). Coronary arteries form by developmental reprogramming of venous cells. Nature, 464, 549-553.
54. Von Gise, A., Zhou, B., Honor, L. B., Ma, Q., Petryk, A., & Pu, W. T. (2011). WT1 regulates epicardial epithelial to mesenchymal transition through β-catenin and retinoic acid signaling pathways. Developmental Biology, 356, 421-431.
55. Prall, O. W., Menon, M. K., Solloway, M. J., et al. (2007). An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation. Cell, 128, 947-959.
56. Christoffels, V. M., Grieskamp, T., Norden, J., Mommersteeg, M. T., Rudat, C., & Kispert, A. (2009). Tbx18 and the fate of epicardial progenitors. Nature, 458, E8-E9.
57. Martin-Puig, S., Wang, Z., & Chien, K. R. (2008). Lives of a heart cell: Tracing the origins of cardiac progenitors. Cell Stem Cell, 2, 320-331.
58. Laugwitz, K. L., Moretti, A., Caron, L., Nakano, A., & Chien, K. R. (2008). Islet1 cardiovascular progenitors: A single source for heart lineages? Development, 135, 193-205.
59. Zeng, B., Ren, X. F., Cao, F., Zhou, X. Y., & Zhang, J. (2011). Developmental patterns and characteristics of epicardial cell markers Tbx18 and Wt1 in murine embryonic heart. Journal of Biomedical Science, 18, 67.
60. Harvey, R. P. (1996). NK-2 homeobox genes and heart development. Developmental Biology, 178, 203-216.
61. Katz, T. C., Singh, M. K., Degenhardt, K., et al. (2012). Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells. Developmental Cell, 22, 639-650.
62. Mikawa, T., & Gourdie, R. G. (1996). Pericardial mesoderm generates a population of coronary smooth muscle cells migrating into the heart along with ingrowth of the epicardial organ. Developmental Biology, 174, 221-232.
63. Manner, J. (1999). Does the subepicardial mesenchyme contribute myocardioblasts to the myocardium of the chick embryo heart? a quail-chick chimera study tracing the fate of the epicardial primordium. The Anatomical Record, 255, 212-226.
64. Gourdie, R. G., Cheng, G., Thompson, R. P., & Mikawa, T. (2000). Retroviral cell lineage analysis in the developing chick heart. Methods in Molecular Biology, 135, 297-304.
65. Perez-Pomares, J. M., Carmona, R., Gonzalez-Iriarte, M., Atencia, G., Wessels, A., & Munoz-Chapuli, R. (2002). Origin of coronary endothelial cells from epicardial mesothelium in avian embryos. International Journal of Developmental Biology, 46, 1005-1013.
66. Guadix, J. A., Carmona, R., Munoz-Chapuli, R., & Perez-Pomares, J. M. (2006). In vivo and in vitro analysis of the vasculogenic potential of avian proepicardial and epicardial cells. Developmental Dynamics, 235, 1014-1026.
67. Kikuchi, K., Gupta, V., Wang, J., et al. (2011). Tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration. Development, 138, 2895-2902.
68. Poss, K. D., Wilson, L. G., & Keating, M. T. (2002). Heart regeneration in zebrafish. Science, 298, 2188-2190.
69. Lepilina, A., Coon, A. N., Kikuchi, K., et al. (2006). A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Cell, 127, 607-619.
70. Kim, J., Wu, Q., Zhang, Y., et al. (2010). PDGF signaling is required for epicardial function and blood vessel formation in regenerating zebrafish hearts. Proceedings of the National Academy of Sciences of the United States of America, 107, 17206-17210.
71. Kikuchi, K., Holdway, J. E., Werdich, A. A., et al. (2010). Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature, 464, 601-605.
72. Hidai, H., Bardales, R., Goodwin, R., Quertermous, T., & Quertermous, E. E. (1998). Cloning of capsulin, a basic helix-loop-helix factor expressed in progenitor cells of the pericardium and the coronary arteries. Mechanisms of Development, 73, 33-43.
73. Lu, J., Richardson, J. A., & Olson, E. N. (1998). Capsulin: A novel bHLH transcription factor expressed in epicardial progenitors and mesenchyme of visceral organs. Mechanisms of Development, 73, 23-32.
74. Robb, L., Mifsud, L., Hartley, L., et al. (1998). Epicardin: A novel basic helix-loop-helix transcription factor gene expressed in epicardium, branchial arch myoblasts, and mesenchyme of developing lung, gut, kidney, and gonads. Developmental Dynamics, 213, 105-113.
75. Vieira, J. M., & Riley, P. R. (2011). Epicardium-derived cells: A new source of regenerative capacity. Heart, 97, 15-19.
76. Laflamme, M. A., & Murry, C. E. (2011). Heart regeneration. Nature, 473, 326-335.
77. Low, T. L., & Goldstein, A. L. (1982). Chemical characterization of thymosin beta 4. The Journal of Biological Chemistry, 257, 1000-1006.
78. Goldstein, A. L. (2007). History of the discovery of the thymosins. Annals of the New York Academy of Sciences, 1112, 1-13.
79. Mannherz, H. G., & Hannappel, E. (2009). The beta-thymosins: Intracellular and extracellular activities of a versatile actin binding protein family. Cell Motility and the Cytoskeleton, 66, 839-851.
80. Smart, N., Hill, A. A., Cross, J. C., & Riley, P. R. (2002). A differential screen for putative targets of the bHLH transcription factor Hand1 in cardiac morphogenesis. Mechanisms of Development, 119(Suppl 1), S65-S71.
81. Hinkel, R., El-Aouni, C., Olson, T., et al. (2008). Thymosin Beta 4 is an essential paracrine factor of embryonic endothelial progenitor cell- mediated cardioprotection. Circulation, 117, 2232-2240.
82. Grant, D. S., Rose, W., Yaen, C., Goldstein, A., Martinez, J., & Kleinman, H. (1999). Thymosin beta 4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis, 3, 125-135.
83. Riley, P. R., & Smart, N. (2009). Thymosin beta 4 induces epicardium-derived neovascularization in the adult heart. Biochemical Society Transactions, 37, 1218-1220.
84. Goldstein, A. L., Hannappel, E., Sosne, G., & Kleinman, H. K. (2012). Thymosin β4: A multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opinion on Biological Therapy, 12, 37-51.
85. Zhou, B., Honor, L. B., Ma, Q., et al. (2012). Thymosin beta 4 treatment after myocardial infarction does not reprogram epicardial cells into cardiomyocytes. Journal of Molecular and Cellular Cardiology, 52, 43-47.
86. Banerjee, I., Zhang, J., Moore-Morris, T., et al. (2012). Thymosin beta 4 is dispensable for murine cardiac development and function. Circulation Research, 110, 456-464.
87. Zhou, B., Honor, L. B., He, H., et al. (2011). Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. The Journal of Clinical Investigation, 121, 1894-1904.
88. Deshane, J., Chen, S., Caballero, S., et al. (2007). Stromal cell-derived factor 1 promotes angiogenesis via a heme oxygenase 1-dependent mechanism. The Journal of Experimental Medicine, 204, 605-618.
89. Niu, J., Azfer, A., Zhelyabovska, O., Fatma, S., & Kolattukudy, P. E. (2008). Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP). Journal of Biological Chemistry, 283, 14542-14551.
90. Moses, K., DeMayo, F., Braun, R., Reecy, J., & Schwartz, R. (2001). Embryonic expression of an Nkx2-5/Cre gene using ROSA26 reporter mice. Genesis, 31, 176-180.
91. Chen, J., Kubalak, S. W., Minamisawa, S., et al. (1998). Selective requirement of myosin light chain 2v in embryonic heart function. Journal of Biological Chemistry, 273, 1252-1256.
92. Rao, D. D., Vorhies, J. S., Senzer, N., & Nemunaitis, J. (2009). SiRNA vs. shRNA: Similarities and differences. Advanced Drug Delivery Reviews, 61, 746-759.
93. Singh, S., Narang, A. S., & Mahato, R. I. (2011). Subcellular fate and off-target effects of siRNA, shRNA, and miRNA. Pharmaceutical Research, 28, 2996-3015.
94. Kara, R. J., Bolli, P., Karakikes, I., et al. (2012). Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation. Circulation Research, 110, 82-93.
95. Passier, R., van Laake, L. W., & Mummery, C. L. (2008). Stem-cell-based therapy and lessons from the heart. Nature, 453, 322-329.
96. Heil, M., Ziegelhoeffer, T., Mees, B., & Schaper, W. (2004). A different outlook on the role of bone marrow stem cells in vascular growth: Bone marrow delivers software not hardware. Circulation Research, 94, 573-574.