Platelet interaction with progenitor cells: Potential implications for regenerative medicine

Konstantinos Stellos; Meinrad Gawaz

doi:10.1160/TH07-02-0147

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(05): 922-929
DOI: 10.1160/TH07-02-0147

Theme Issue Article

Schattauer GmbH

Platelet interaction with progenitor cells: Potential implications for regenerative medicine

Authors

Konstantinos Stellos

¹Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Tübingen, Germany
Meinrad Gawaz

¹Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Tübingen, Germany

Abstract

Summary

Circulating endothelial progenitor cells have been shown to instigate new vessel formation via angiogenesis and neovascularisation and to induce ongoing vascular and tissue repair by domiciliation to sites of vascular or tissue damage. However, the mechanisms that recruit circulating endothelial progenitor cells towards vascular lesions and regulate repair mechanisms of ischemic peripheral organs are poorly described. Domiciliation of endothelial progenitor cells in peripheral tissue is a multi-step cascade including initial adhesion to subendothelial matrix or endothelium, transmigration and invasion of the target tissue. Platelets are the first circulating blood cells that interact with the injured vessel wall. They contain a number of growth factors, chemokines, cytokines and adhesive proteins that are released or surface-expressed upon platelet activation including adhesion. Recent studies suggest that platelet interaction with endothelial progenitor cells influences chemotaxis, adhesion, activation and differentiation of progenitor cells. Release of the chemokine SDF-1 from platelets enhances neovascularization through mobilization of progenitor cells. Adherent platelets recruit bone marrow-derived progenitor cells to arterial thrombi in vitroand in vivoand induce their subsequent differentiation towards an endothelial phenotype. Moreover, platelet accumulation in a co-culture system with CD34⁺ progenitor cells results in the differentiation of the latter to macrophages in vitro. Although further studies are needed to elucidate the mechanisms that platelets determine the fate of endothelial progenitor cells into vascular lesions, platelet interaction with progenitor cells seems to play a decisive role in vascular and tissue regeneration.

Keywords

Endothelial progenitor cells - platelets - vascular adhesion - endothelial injury

Full Text

References

References
1 Herzog EL, Chai L, Krause DS. Plasticity of marrow- derived stem cells. Blood 2003; 102: 3483-3493.
2 Docheva D, Popov C, Mutschler W. et al. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med 2007; 11: 21-38.
3 Mendez-Ferrer S, Ellison GM, Torella D. et al. Resident progenitors and bone marrow stem cells in myocardial renewal and repair. Nat Clin Pract Cardiovasc Med 2006; 3 (Suppl. 01) S83-89.
5 Yin T, Li L. The stem cell niches in bone. J Clin Invest 2006; 116: 1195-1201.
6 Dimmeler S, Zeiher AM, Schneider MD. Unchain my heart: the scientific foundations of cardiac repair. J Clin Invest 2005; 115: 572-583.
7 Bobis S, Jarocha D, Majka M. Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol 2006; 44: 215-230.
8 Phinney DG, Isakova I. Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 2005; 11: 1255-1265.
9 Murry C, Reinecke H, Pabon L. Regeneration Gaps. Observations on Stem Cells and Cardiac Repair. J Am Coll Cardiol 2006; 47: 1777-1785.
10 Shafritz DA, Oertel M, Menthena A. et al. Liver stem cells and prospects for liver reconstitution by transplanted cells. Hepatology 2006; 43: S89-98.
11 Cantley L. Adult stem cells in the repair of the injured renal tubule. Nat Clin Pract Nephrol 2005; 1: 22-32.
12 Dietrich J, Kempermann G. Role of endogenous neural stem cells in neurological disease and brain repair. Adv Exp Med Biol 2006; 557: 191-220.
13 Asahara T, Murohara T, Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-967.
14 Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004; 95: 343-353.
15 Sata M, Saiura A, Kunisato A. et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002; 8: 403-409.
16 Santoni-Rugiu E, Jelnes P, Thorgeirsson SS. et al. Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion. Apmis 2005; 113: 876-902.
17 Laflamme MA, Murry CE. Regenerating the heart. Nat Biotechnol 2005; 23: 845-856.
18 Rafii S, Lyden D. Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 2003; 9: 702-712.
19 Lyden D, Hattori K, Dias S. et al. Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001; 7: 1194-1201.
20 Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med 2004; 8: 498-508.
21 Iwami Y, Masuda H, Asahara T. Endothelial progenitor cells: past, state of the art, and future. J Cell Mol Med 2004; 8: 488-497.
22 Langer H, May AE, Daub K. et al. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro. Circ Res 2006; 98: e2-10.
23 Massberg S, Konrad I, Schurzinger K. et al. Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med 2006; 203: 1221-1233.
24 de Boer HC, Verseyden C, Ulfman LH. et al. Fibrin and activated platelets cooperatively guide stem cells to a vascular injury and promote differentiation towards an endothelial cell phenotype. Arterioscler Thromb Vasc Biol 2006; 26: 1653-1659.
25 Lev EI, Estrov Z, Aboulfatova K. et al. Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix. Thromb Haemost 2006; 96: 498-504.
26 Shi Q, Rafii S, Wu MH. et al. Evidence for circulating bone marrow-derived endothelial cells. Blood 1998; 92: 362-367.
27 Werner N, Nickenig G. Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy?. Arterioscler Thromb Vasc Biol 2006; 26: 257-266.
28 Ingram DA, Caplice NM, Yoder MC. Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood 2005; 106: 1525-1531.
29 Szmitko PE, Fedak PW, Weisel RD. et al. Endothelial progenitor cells: new hope for a broken heart. Circulation 2003; 107: 3093-3100.
30 Yang C, Zhang ZH, Li ZJ. et al. Enhancement of neovascularization with cord blood CD133+ cell-derived endothelial progenitor cell transplantation. Thromb Haemost 2004; 91: 1202-1212.
31 Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension 2005; 45: 321-325.
32 Kalka C, Masuda H, Takahashi T. et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 2000; 97: 3422-3427.
33 Assmus B, Schachinger V, Teupe C. et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE- AMI). Circulation 2002; 106: 3009-3017.
34 Numaguchi Y, Sone T, Okumura K. et al. The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 2006; 4: I114-119.
35 Xu Q, Zhang Z, Davison F. et al. Circulating progenitor cells regenerate endothelium of vein graft atherosclerosis, which is diminished in ApoE-deficient mice. Circ Res 2003; 93: e76-86.
36 Werner N, Kosiol S, Schiegl T. et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353: 999-1007.
37 Schmidt-Lucke C, Rossig L, Fichtlscherer S. et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 111: 2981-2987.
38 Heiss C, Keymel S, Niesler U. et al. Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 2005; 45: 1441-1448.
39 Urbich C, Dimmeler S. Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors. Kidney Int 2005; 67: 1672-1676.
40 Assmus B, Honold J, Schachinger V. et al. Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 2006; 355: 1222-1232.
41 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.
42 Kastrup J, Ripa RS, Wang Y. et al. Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy?. Eur Heart J 2006; 27: 2748-2754.
43 Ripa RS, Jorgensen E, Wang Y. et al. Stem cell mobilization induced by subcutaneous granulocytecolony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial. Circulation 2006; 113: 1983-1992.
44 Honold J, Lehmann R, Heeschen C. et al. Effects of granulocyte colony stimulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol 2006; 26: 2238-2243.
45 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.
46 Menasche P. Stem cells for clinical use in cardiovascular medicine: current limitations and future perspectives. Thromb Haemost 2005; 94: 697-701.
47 Emanueli C, Lako M, Stojkovic M. et al. In search of the best candidate for regeneration of ischemic tissues: are embryonic/fetal stem cells more advantageous than adult counterparts?. Thromb Haemost 2005; 94: 738-749.
48 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115: 3378-3384.
49 Gorlach A, Brandes RP, Bassus S. et al. Oxidative stress and expression of p22phox are involved in the up-regulation of tissue factor in vascular smooth muscle cells in response to activated platelets. Faseb J 2000; 14: 1518-1528.
50 Rhee JS, Black M, Schubert U. et al. The functional role of blood platelet components in angiogenesis. Thromb Haemost 2004; 92: 394-402.
51 Spencer E, Tokunaga A, Hunt T. Insuline-like growth factor binding protein-3 is present in the alphagranules of platelets. Endocrinology 1993; 132: 996-1001.
52 Oike Y, Yasunaga K, Ito Y. et al. Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration. Proc Natl Acad Sci USA 2003; 100: 9494-9499.
53 Pintucci G, Froum S, Pinnell J. et al. Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). Thromb Haemost 2002; 88: 834-842.
54 Wartiovaara U, Salven P, Mikkola H. et al. Peripheral blood platelets express VEGF-C and VEGF which are released during platelet activation. Thromb Haemost 1998; 80: 171-175.
55 Lesurtel M, Graf R, Aleil B. et al. Platelet-derived serotonin mediates liver regeneration. Science 2006; 312: 104-107.
56 Nocito A, Georgiev P, Dahm F. et al. Platelets and platelet-derived serotonin promote tissue repair after normothermic hepatic ischemia in mice. Hepatology 2007; 45: 369-376.
57 Anitua E, Andia I, Ardanza B. et al. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 2004; 91: 4-15.
58 Massberg S, Enders G, Matos F. et al. Fibrinogen deposition at the postischemic vessel wall promotes platelet adhesion during ischemia-reperfusion in vivo. Blood 1999; 94: 3829-3838.
59 Frenette P, Denis C, Weiss L. et al. P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo. J Exp Med 2000; 191: 1413-1422.
60 Yang J, Furie B, Furie B. The biology of P-selectin glycoprotein ligand-1: its role as a selectin counterreceptor in leukocyte-endothelial and leukocyte-platelet interaction. Thromb Haemost 1999; 81: 1-7.
61 Simon D, Chen Z, Xu H. et al. Platelet glycoprotein ibalpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
62 Santoso S, Sachs DH, Kroll H. et al. The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. J Exp Med 2002; 196: 679-691.
63 Daub K, Langer H, Seizer P. et al. Platelets induce differentiation of human CD34+-progenitor cells into foam cells and endothelial cells. Faseb J 2006; 20: 2559-2561.
64 Dickfeld T, Lengyel E, May AE. et al. Transient interaction of activated platelets with endothelial cells induces expression of monocyte-chemoattractant protein- 1 via a p38 mitogen-activated protein kinase mediated pathway. Implications for atherogenesis. Cardiovasc Res 2001; 49: 189-199.
65 Gawaz M, Page S, Massberg S. et al. Transient platelet interaction induces MCP-1 production by endothelial cells via I kappa B kinase complex activation. Thromb Haemost 2002; 88: 307-314.
66 May AE, Kalsch T, Massberg S. et al. Engagement of glycoprotein IIb/IIIa (alpha(IIb)beta3) on platelets upregulates CD40L and triggers CD40L-dependent matrix degradation by endothelial cells. Circulation 2002; 106: 2111-2117.
67 Gawaz M, Brand K, Dickfeld T. et al. Platelets induce alterations of chemotactic and adhesive properties of endothelial cells mediated through an interleukin- 1-dependent mechanism. Implications for atherogenesis. Atherosclerosis 2000; 148: 75-85.
68 Stellos K, Gawaz M. Platelets and stromal cell-derived factor-1 in progenitor cell recruitment. Semin Thromb Hemost 2007; 33: 159-164.
69 Langer HF, May AE, Vestweber D. et al. Platelet-induced differentiation of endothelial progenitor cells. Semin Thromb Hemost 2007; 33: 136-143.
70 Daub K, Lindemann S, Langer H. et al. The evil in atherosclerosis: adherent platelets induce foam cell formation. Semin Thromb Hemost 2007; 33: 173-178.
71 Lapidot T, Dar A, Kollet O. How do stem cells find their way home?. Blood 2005; 106: 1901-1910.
72 Massberg S, Gawaz M, Gruner S. et al. A crucial role of glycoprotein VI for platelet recruitment to the injured arterial wall in vivo. J Exp Med 2003; 197: 41-49.
73 Chen J, Lopez JA. Interactions of platelets with subendothelium and endothelium. Microcirculation 2005; 12: 235-246.
74 Aiuti A, Webb IJ, Bleul C. et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997; 185: 111-120.
75 Yamaguchi J, Kusano KF, Masuo O. et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 2003; 107: 1322-1328.
76 Jin DK, Shido K, Kopp HG. et al. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nat Med 2006; 12: 557-567.
77 Gawaz M. Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium. Cardiovasc Res 2004; 61: 498-511.
78 Stellos K, Langer H, Bigalke B. et al. Platelet-derived SDF-1 regulates recruitment and differentiation of human CD34+ progenitor cells. Hämostaseologie 2007; 27 Abstract P044.
79 Gawaz M, Neumann FJ, Ott I. et al. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996; 93: 229-237.
80 Sarma J, Laan CA, Alam S. et al. Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 2002; 105: 2166-2171.
81 Furman MI, Barnard MR, Krueger LA. et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol 2001; 38: 1002-1006.
82 Fateh-Moghadam S, Htun P, Tomandl B. et al. Hyperresponsiveness of platelets in ischemic stroke. Thromb Haemost 2007; 97: 974-978.
83 Htun P, Fateh-Moghadam S, Tomandl B. et al. Course of platelet activation and platelet-leukocyte interaction in cerebrovascular ischemia. Stroke 2006; 37: 2283-2287.
84 Heeschen C, Dimmeler S, Hamm CW. et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 2003; 348: 1104-1111.
85 Garlichs CD, Eskafi S, Raaz D. et al. Patients with acute coronary syndromes express enhanced CD40 ligand/ CD154 on platelets. Heart 2001; 86: 649-655.
86 Maree AO, Fitzgerald DJ. Variable platelet response to aspirin and clopidogrel in atherothrombotic disease. Circulation 2007; 115: 2196-2207.
87 Bliden KP, DiChiara J, Tantry US. et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate?. J Am Coll Cardiol 2007; 49: 657-666.
88 Moshfegh K, Redondo M, Julmy F. et al. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000; 36: 699-705.
89 Geisler T, Langer H, Wydymus M. et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J 2006; 27: 2420-2425.
90 Geisler T, Anders N, Paterok M. et al. Platelet response to clopidogrel is attenuated in diabetic patients undergoing coronary stent implantation. Diabetes Care 2007; 30: 372-374.
91 Hochholzer W, Trenk D, Bestehorn HP. et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol 2006; 48: 1742-1750.
92 Neumann FJ, Zohlnhofer D, Fakhoury L. et al. Effect of glycoprotein IIb/IIIa receptor blockade on platelet- leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction. J Am Coll Cardiol 1999; 34: 1420-1426.
93 Xiao Z, Theroux P. Clopidogrel inhibits plateletleukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome. J Am Coll Cardiol 2004; 43: 1982-1988.
94 Becker RC, Bovill EG, Corrao JM. et al. Platelet activation determined by flow cytometry persists despite antithrombotic therapy in patients with unstable angina and non-Q-wave myocardial infarction. J Thromb Thrombolysis 1994; 1: 95-100.
95 Chung T, Connor D, Joseph J. et al. Platelet activation in acute pulmonary embolism. J Thromb Haemost 2007; 5: 918-924.
96 Choudhury A, Chung I, Blann AD. et al. Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P-selectin as indexes of platelet function in atrial fibrillation: a comparison of "healthy control subjects" and "disease control subjects" in sinus rhythm. J Am Coll Cardiol 2007; 49: 1957-1964.
97 Bigalke B, Lindemann S, Ehlers R. et al. Expression of platelet collagen receptor glycoprotein VI is associated with acute coronary syndrome. Eur Heart J 2006; 27: 2165-2169.
98 Samara WM, Gurbel PA. The role of platelet receptors and adhesion molecules in coronary artery disease. Coron Artery Dis 2003; 14: 65-79.
99 Gawaz M. Platelets in the onset of atherosclerosis. Blood Cells Mol Dis 2006; 36: 206-210.