Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains

Michal Heger; Johan F. Beek; Nicanor I. Moldovan; Chantal M. A. M. van der Horst; Martin J. C. van Gemert

doi:10.1160/TH04-05-0291

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(02): 242-256
DOI: 10.1160/TH04-05-0291

Review Article

Schattauer GmbH

Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains

A theoretical study

Michal Heger

¹Laser Center and Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Johan F. Beek

¹Laser Center and Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Nicanor I. Moldovan

²Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA

,

Chantal M. A. M. van der Horst

³Department of Plastic, Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

,

Martin J. C. van Gemert

¹Laser Center and Reconstructive, and Hand Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

› Author Affiliations

Abstract

Summary

For the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the thresh-old damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.

Keywords

Port wine stains - thrombus organization - neovascularization - endothelial progenitor cells - procoagulant pharmaceuticals

Full Text

References

References
1 Anderson RR, Parrish JA. Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation.. Science 1983; 220: 524-7.
2 van Gemert MJC, Welch AJ, Pickering JW. et al Laser treatment of port wine stains. In: Optical-thermal response of laser-irradiated tissue. New York: Plenum Press; 1995
3 Tunnell JW, Wang LV, Anvari B. Optimum pulse duration and radiant exposure for vascular laser therapy of dark port-wine skin: a theoretical study.. Appl Opt 2003; 42: 1367-78.
4 Braverman IM. The cutaneous microcirculation.. J Investig Dermatol Symp Proc 2000; 5: 3-9.
5 Verkruysse W, Lucassen GW, van Gemert MJ. Simulation of color of port wine stain skin and its dependence on skin variables.. Lasers Surg Med 1999; 25: 131-9.
6 Kelly KM, Nanda VS, Nelson JS. Treatment of port-wine stain birthmarks using the 1.5-msec pulsed dye laser at high fluences in conjunction with cryogen spray cooling.. Dermatol Surg 2002; 28: 309-13.
7 Tunnell JW, Chang DW, Johnston C. et al Effects of cryogen spray cooling and high radiant exposures on selective vascular injury during laser irradiation of human skin.. Arch Dermatol 2003; 139: 743-50.
8 Dai T, Pikkula BM, Tunnell JW. et al Thermal response of human skin epidermis to 595-nm laser irradiation at high incident dosages and long pulse durations in conjunction with cryogen spray cooling: an ex vivo study.. Lasers Surg Med 2003; 33: 16-24.
9 Lucassen GW, Verkruysse W, Keijzer M. et al Light distributions in a port wine stain model containing multiple cylindrical and curved blood vessels.. Lasers Surg Med 1996; 18: 345-57.
10 Hohenleutner U, Hilbert M, Wlotzke U. et al Epidermal damage and limited coagulation depth with the flashlamp-pumped pulsed dye laser: a histochemical study.. J Invest Dermatol 1995; 104: 798-802.
11 Fiskerstrand EJ, Svaasand LO, Kopstad G. et al Photothermally induced vessel-wall necrosis after pulsed dye laser treatment: lack of response in portwine stains with small sized or deeply located vessels.. J Invest Dermatol 1996; 107: 671-5.
12 Fiskerstrand EJ, Svaasand LO, Kopstad G. et al Laser treatment of port wine stains: therapeutic outcome in relation to morphological parameters.. Br J Dermatol 1996; 134: 1039-43.
13 Verkruysse W, Pickering JW, Beek JF. et al Modeling the effect of wavelength on the pulsed dye laser treatment of port wine stains.. Appl Optics 1993; 32: 393-8.
14 van Gemert MJ, Smithies DJ, Verkruysse W. et al Wavelengths for port wine stain laser treatment: influence of vessel radius and skin anatomy.. Phys Med Biol 1997; 42: 41-50.
15 Tan OT, Carney JM, Margolis R. et al Histologic responses of port-wine stains treated by argon, carbon dioxide, and tunable dye lasers. A preliminary report.. Arch Dermatol 1986; 122: 1016-22.
16 Tan OT, Morelli JG, Whitaker D. et al Ultrastructural changes in red blood cells following pulsed irradiation in vitro.. J Invest Dermatol 1989; 92: 100-4.
17 Black JF, Barton JK. Chemical and structural changes in blood undergoing laser photocoagulation.. Photochem Photobiol 2004; 80: 89-97.
18 Greve B, Raulin C. Prospective study of port wine stain treatment with dye laser: comparison of two wavelengths (585 nm vs. 595 nm) and two pulse durations (0.5 milliseconds vs. 20 milliseconds).. Lasers Surg Med 2004; 34: 168-73.
19 Tan OT, Whitaker D, Garden JM. et al Pulsed dye laser (577 nm) treatment of portwine stains: ultrastructural evidence of neovascularization and mast cell degranulation in healed lesions.. J Invest Dermatol 1988; 90: 395-8.
20 Puri RN, Colman RW. ADP-induced platelet activation.. Crit Rev Biochem Mol Biol 1997; 32: 437-502.
21 Brass LF. Thrombin and platelet activation.. Chest 2003; 124 (Suppl. 03) 18S-25S.
22 Lazarus AH, Song S, Crow AR. Understanding platelet function through signal transduction.. Transfus Med Rev 2003; 17: 45-56.
23 Dahlbäck B. Blood coagulation.. Lancet 2000; 355: 1627-32.
24 Lentz BR. Exposure of platelet membrane phosphatidylserine regulates blood coagulation.. Prog Lipid Res 2003; 42: 423-38.
25 Giesen PL, Rauch U, Bohrmann B. et al Bloodborne tissue factor: another view of thrombosis.. Proc Natl Acad Sci U S A 1999; 96: 2311-5.
26 Rauch U, Bonderman D, Bohrmann B. et al Transfer of tissue factor from leukocytes to platelets is mediated by CD15 and tissue factor.. Blood 2000; 96: 170-5.
27 Falati S, Liu Q, Gross P. et al Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin.. J Exp Med 2003; 197: 1585-98.
28 Nilsson AMK, Lucassen GW, Verkruysse W. et al Changes in optical properties of human whole blood in vitro due to slow heating.. Photochem Photobiol 1997; 65: 366-73.
29 San Biagio PL, Martorana V, Emanuele A. et al Interacting processes in protein coagulation.. Proteins 1999; 37: 116-20.
30 Falati S, Gross P, Merrill-Skoloff G. et al Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse.. Nat Med 2002; 8: 1175-81.
31 Morrissey JH. Tissue factor: an enzyme cofactor and true receptor.. Thromb Haemost 2001; 86: 66-74.
32 Engelmann B, Luther T, Muller I. Intravascular tissue factor pathway – a model for rapid initiation of coagulation within the blood vessel.. Thromb Haemost 2003; 89: 3-8.
33 Coughlin SR. Thrombin signaling and protease-activated receptors.. Nature 2000; 407: 258-64.
34 Jackson SP, Nesbitt WS, Kulkarni S. Signaling events underlying thrombus formation.. J Thromb Haemost 2003; 1: 1602-12.
35 van Mourik JA, Romani de Wit T, Voorberg J. Biogenesis and exocytosis of Weibel-Palade bodies.. Histochem Cell Biol 2002; 117: 113-22.
36 Klarenbach SW, Chipiuk A, Nelson RC. et al Differential actions of PAR2 and PAR1 in stimulating human endothelial cell exocytosis and permeability: the role of Rho-GTPases.. Circ Res 2003; 92: 272-8.
37 Minami T, Sugiyama A, Wu SQ. et al Thrombin and phenotypic modulation of the endothelium.. Arterioscler Thromb Vasc Biol 2004; 24: 41-53.
38 Kaur J, Woodman RC, Kubes P. P38 MAPK: critical molecule in thrombin-induced NF-kappa B-dependent leukocyte recruitment.. Am J Physiol Heart Circ Physiol 2003; 284: H1095-103.
39 Zimmerman GA, McIntyre TM, Prescott SM. et al The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis.. Crit Care Med 2002; 30 (Suppl. 05) Suppl S294-301.
40 Hughes PE, Pfaff M. Integrin affinity modulation.. Trends Cell Biol 1998; 8: 359-64.
41 Ruggeri ZM. Mechanisms of shear-induced platelet adhesion and aggregation.. Thromb Haemost 1993; 70: 119-23.
42 Ruggeri ZM. Structure and function of von Willebrand factor.. Thromb Haemost 1999; 82: 576-84.
43 Goto S, Ikeda Y, Saldivar E. et al Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions.. J Clin Invest 1998; 101: 479-86.
44 Bombeli T, Schwartz BR, Harlan JM. Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha.. J Exp Med 1998; 187: 329-39.
45 Goel MS, Diamond SL. Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma.. Blood 2002; 100: 3797-803.
46 Hermand P, Gane P, Huet M. et al Red cell ICAM-4 is a novel ligand for platelet-activated alphaIIbbeta3 integrin.. J Biol Chem 2003; 278: 4892-8.
47 Ni H, Yuen PS, Papalia JM. et al Plasma fibronectin promotes thrombus growth and stability in injured arterioles.. Proc Natl Acad Sci U S A 2003; 100: 2415-9.
48 Quinn MJ, Byzova TV, Qin J. et al Integrin alphaIIbbeta3 and its antagonism.. Arterioscler Thromb Vasc Biol 2003; 23: 945-52.
49 Rosen ED, Raymond S, Zollman A. et al Laser-induced noninvasive vascular injury models in mice generate platelet and coagulation-dependent thrombi.. Am J Pathol 2001; 158: 1613-22.
50 Rosenblum I W. Platelet adhesion and aggregation without endothelial denudation or exposure of basal lamina and/or collagen.. J Vasc Res 1997; 34: 409-17.
51 Mordon S, Begu S, Buys B. et al Study of platelet behavior in vivo after endothelial stimulation with laser irradiation using fluorescence intravital videomicroscopy and PEGylated liposome staining.. Microvasc Res 2002; 64: 316-25.
52 Mordon S, Desmettre T, Devoiselle JM. Laser irradiation of the vessel wall can induce PEGylated liposomes adhesion on the endothelium: an in vivo model for studying site-selective delivery of diagnostic or therapeutic agents. In: Optical diagnostics of living cells.. SPIE 2001; 4: 20-9.
53 Varnon D, Jackson DE, Shenkman B. et al Platelet/ endothelial cell adhesion molecule-1 serves as a costimulatory agonist receptor that modulates integrin-dependent adhesion and aggregation of human platelets.. Blood 1998; 91: 500-7.
54 Kumar V, Cotran RS, Robbins SL. Basic pathology, 7 th edition. Philadelphia: W.B: Saunders Company; 2003
55 Leu HJ, Feigl W, Susani M. Angiogenesis from mononuclear cells in thrombi.. Virchows Arch A Pathol Anat Histopathol 1987; 411: 5-14.
56 Leu HJ, Feigl W, Susani M. et al Differentiation of mononuclear blood cells into macrophages, fibroblasts and endothelial cells in thrombus organization.. Exp Cell Biol 1988; 56: 201-10.
57 Wakefield TW, Linn MJ, Henke PK. et al Neovascularization during venous thrombosis organization: a preliminary study.. J Vasc Surg 1999; 30: 885-92.
58 Moldovan NI, Goldschmidt-Clermont PJ, Parker-Thornburg J. et al Contribution of monocytes/macrophages to compensatory neovascularization: the drilling of metalloelastase-positive tunnels in ischemic myocardium.. Circ Res 2000; 87: 378-84.
59 Moldovan I N. Role of monocytes and macrophages in adult angiogenesis: a light at the tunnel's end.. J Hematother Stem Cell Res 2002; 11: 179-94.
60 Moldovan I N, Asahara T. Role of blood mononuclear cells in recanalization and vascularization of thrombi: past, present, and future.. Trends Cardiovasc Med 2003; 13: 265-69.
61 McGuinness CL, Humphries J, Waltham M. et al Recruitment of labeled monocytes by experimental venous thrombi.. Thromb Haemost 2001; 85: 1018-24.
62 Waltham M, Burnard KG, Collins M. et al Vascular endothelial growth factor enhances venous thrombus recanalisation and organization.. Thromb Haemost 2003; 89: 169-76.
63 Waltham M, Burnand KG, Collins M. et al Vascular endothelial growth factor and basic fibroblast growth factor are found in resolving venous thrombi.. J Vasc Surg 2000; 32: 988-96.
64 Scotland RS, Vallance PJ, Ahluwalia A. Endogenous factors involved in regulation of tone of arterial vasa vasorum: implications for conduit vessel physiology.. Cardiovasc Res 2000; 46: 403-11.
65 Trelles MA, Verkruysse W, Mayayo E. et al Vessel hyalinization phenomenon in the laser treatment of tuberous hemangiomas and port wine stains.. J Dermatol Sci 1995; 9: 70-3.
66 Trelles MA, Svaasand LO, Vélez M. et al Possible mechanisms for an irregular vessel coagulation when long laser pulses are used in the treatment of port-wine stains.. J Dermatol Sci 1996; 13: 161-6.
67 Fernandez Pujol B, Lucibello FC, Gehling UM. et al Endothelial-like cells derived from human CD14 positive monocytes.. Differentiation 2000; 65: 287-300.
68 Harraz M, Jiao C, Hanlon HD. et al CD34- bloodderived human endothelial cell progenitors.. Stem Cells 2001; 19: 304-12.
69 Schmeisser A, Garlichs CD, Zhang H. et al Monocytes coexpress endothelial and macrophagocytic lineage markers and form cord-like structures in Matrigel under angiogenic conditions.. Cardiovasc Res 2001; 49: 671-80.
70 Singh I, Burnand KG, Collins M. et al Failure of thrombus to resolve in urokinase-type plasminogen activator gene-knockout mice: rescue by normal bone marrow-derived cells.. Circulation 2003; 107: 869-75.
71 Simon I D, Ezratty AM, Francis SA. et al Fibrin( ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18): a nonplasmin fibrinolytic pathway.. Blood 1993; 82: 2414-22.
72 Enjolras O, Mulliken JB. The current management of vascular birthmarks.. Pediatr Dermatol 1993; 10: 311-33.
73 Carmeliet P. Angiogenesis in health and disease.. Nat Med 2003; 9: 653-60.
74 Metz CN. Fibrocytes: a unique cell population implicated in wound healing.. Cell Mol Life Sci 2003; 60: 1342-50.
75 Kawamoto A, Gwon HC, Iwaguro H. et al Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.. Circulation 2001; 103: 634-7.
76 Kocher AA, Schuster MD, Szabolcs MJ. et al Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodelling and improves cardiac function.. Nat Med 2001; 7: 430-6.
77 Kalka C, Masuda H, Takahashi T. et al Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization.. Proc Natl Acad Sci U S A 2000; 97: 3422-7.
78 Murohara T, Ikeda H, Duan J. et al Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization.. J Clin Invest 2000; 105: 1527-36.
79 Grant MB, May WS, Caballero S. et al Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization.. Nat Med 2002; 8: 607-12.
80 Sengupta N, Caballero S, Mames RN. et al The role of adult bone marrow-derived stem cells in choroidal neovascularization.. Invest Ophthalmol Vis Sci 2003; 44: 4908-13.
81 Asahara T, Masuda H, Takahashi T. et al Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization.. Circ Res 1999; 85: 221-8.
82 Shaw JP, Basch R, Shamamian P. Hematopoietic stem cells and endothelial cell precursors express Tie-2, CD31 and CD45.. Blood Cells Mol Dis 2004; 32: 168-75.
83 Gill M, Dias S, Hattori K. et al Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells.. Circ Res 2001; 88: 167-74.
84 Hu Y, Davison F, Zhang Z. et al Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells.. Circulation 2003; 108: 3122-7.
85 Fujiyama S, Amano K, Uehira K. et al Bone marrow monocyte lineage cells adhere on injured endothelium in a monocyte chemoattractant protein-1-dependent manner and accelerate reendothelialization as endothelial progenitor cells.. Circ Res 2003; 93: 980-9.
86 Jain RK. Molecular regulation of vessel maturation.. Nat Med 2003; 9: 685-93.
87 Scholz D, Cai WJ, Schaper W. Arteriogenesis, a new concept of vascular adaptation in occlusive disease.. Angiogenesis 2001; 4: 247-57.
88 Furie B, Furie BC, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion.. Thromb Haemost 2001; 86: 214-21.
89 St Hill CA, Alexander SR, Walcheck B. Indirect capture augments leukocyte accumulation on P-selectin in flowing whole blood.. J Leukoc Biol 2003; 73: 464-71.
90 Forlow SB, McEver RP, Nollert MU. Leukocyteleukocyte interactions mediated by platelet microparticles under flow.. Blood 2000; 95: 1317-23.
91 Valente AJ, Rozek MM, Sprague EA. et al Mechanisms in intimal monocyte-macrophage recruitment. A special role for monocyte chemotactic protein-1.. Circulation 1992; 86 (6Suppl) III20-5.
92 Herrick S, Blanc-Brude O, Gray A. et al Fibrinogen.. Int J Biochem Cell Biol 1999; 31: 741-6.
93 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: 189-99.
94 Tezono K, Sarker KP, Kikuchi H. et al Bioactivity of the vascular endothelial growth factor trapped in fibrin clots: production of IL-6 and IL-8 in monocytes by fibrin clots.. Haemostasis 2001; 31: 71-9.
95 Barleon B, Sozzani S, Zhou D. et al Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1.. Blood 1996; 87: 3336-43.
96 Wahl SM, Allen JB, Weeks BS. et al Transforming growth factor beta enhances integrin expression and type IV collagenase secretion in human monocytes.. Proc Natl Acad Sci U S A 1993; 90: 4577-81.
97 Krettek A, Ostergren-Lunden G, Fager G. et al Expression of PDGF receptors and ligand-induced migration of partially differentiated human monocyte-derived macrophages. Influence of IFN-gamma and TGFbeta.. Atherosclerosis 2001; 156: 267-75.
98 Siegbahn A, Hammacher A, Westermark B. et al Differential effects of the various isoforms of plateletderived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes.. J Clin Invest 1990; 85: 916-20.
99 Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4.. J Immunol 2001; 167: 2887-94.
100 Meissner MH, Zierler BK, Bergelin RO. et al Coagulation, fibrinolysis, and recanalization after acute deep venous thrombosis.. J Vasc Surg 2002; 35: 278-85.
101 Colotta F, Sciacca FL, Sironi M. et al Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin.. Am J Pathol 1994; 144: 975-85.
102 Humphries J, McGuinness CL, Smith A. et al Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi.. J Vasc Surg 1999; 30: 894-900.
103 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: 307-14.
104 Asahara T, Takahashi T, Masuda H. et al VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells.. EMBO J 1999; 18: 3964-72.
105 Kalka C, Masuda H, Takahashi T. et al Vascular endothelial growth factor(165) gene transfer augments circulating endothelial progenitor cells in human subjects.. Circ Res 2000; 86: 1198-1202.
106 Peichev M, Naiyer AJ, Pereira D. et al Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors.. Blood 2000; 95: 952-8.
107 Gehling UM, Ergun S, Schumacher U. et al In vitro differentiation of endothelial cells from AC133-positive progenitor cells.. Blood 2000; 95: 3106-12.
108 Reyes M, Dudek A, Jahagirdar B. et al Origin of endothelial progenitors in human postnatal bone marrow.. J Clin Invest 2002; 109: 337-46.
109 Zhao Y, Glesne D, Huberman E. A human peripheral blood monocyte-derived subset acts as pluripotent stem cells.. Proc Natl Acad Sci USA 2003; 100: 2426-31.
110 Asahara T, Murohara T, Sullivan A. et al Isolation of putative progenitor endothelial cells for angiogenesis.. Science 1997; 275: 964-7.
111 Takakura N, Watanabe T, Suenobu S. et al A role for hematopoietic stem cells in promoting angiogenesis.. Cell 2000; 102: 199-209.
112 Rehman J, Li J, Orschell CM. et al Peripheral blood "endothelial progenitor cells" are derived from monocyte/macrophages and secrete angiogenic growth factors.. Circulation 2003; 107: 1164-9.
113 Nakul-Aquaronne D, Bayle J, Frelin C. Coexpression of endothelial markers and CD14 by cytokine mobilized CD34+ cells under angiogenic stimulation.. Cardiovasc Res 2003; 57: 816-23.
114 Masuda H, Asahara T. Post-natal endothelial progenitor cells for neovascularization in tissue regeneration.. Cardiovasc Res 2003; 58: 390-8.
115 Hristov M, Erl W, Weber PC. Endothelial progenitor cells: mobilization, differentiation, and homing.. Arterioscler Thromb Vasc Biol 2003; 23: 1185-9.
116 Schatteman GC, Awad O. Hemangioblasts, angioblasts, and adult endothelial cell progenitors.. Anat Rec 2004; 276 A 13-21.
117 Reyes M, Lund T, Lenvik T. et al Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells.. Blood 2001; 98: 2615-25.
118 Jiang Y, Jahagirdar BN, Reinhardt RL. et al Pluripotency of mesenchymal stem cells derived from adult marrow.. Nature 2002; 418: 41-9.
119 Abrink M, Gobl AE, Huang R. et al Human cell lines U-937, THP-1 and Mono Mac 6 represent relatively immature cells of the monocyte-macrophage cell lineage.. Leukemia 1994; 8: 1579-84.
120 Syrjala M, Ruutu T, Jansson SE. A flow cytometric assay of CD34-positive cell populations in the bone marrow.. Br J Haematol 1994; 88: 679-84.
121 Shepard JL, Zon I L. Developmental derivation of embryonic and adult macrophages.. Curr Opin Hematol 2000; 7: 3-8.
122 Harmening DM. Clinical hematology and fundamentals of hemostasis, 4 th edition. Philadelphia; F.A: Davis Company; 2002
123 Takahashi T, Kalka C, Masuda H. et al Ischemiaand cytokine-induced mobilization of bone marrowderived endothelial progenitor cells for neovascularization.. Nat Med 1999; 5: 434-8.
124 Ziegelhoeffer T, Fernandez B, Kostin S. et al Bone marrow-derived cells do not incorporate into the adult growing vasculature.. Circ Res 2004; 94: 230-8.
125 Hur J, Yoon CH, Kim HS. et al Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis.. Arterioscler Thromb Vasc Biol 2004; 24: 288-93.
126 Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system.. Nat Med 2003; 9: 677-84.
127 Finley JL, Barsky SH, Geer DE. Healing of port wine stains after argon laser therapy.. Arch Dermatol 1981; 117: 486-9.
128 Nguyen CM, Yohn JJ, Huff C. et al Facial port wine stains in childhood: prediction of the rate of improvement as a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser.. Br J Dermatol 1998; 138: 821-5.
129 Genevois O, Paques M, Simonutti M. et al Microvascular remodelling after occlusion-recanalization of a branch retinal vein in rats.. Invest Ophthalmol Vis Sci 2004; 45: 594-600.
130 Tomita M, Yamada H, Adachi Y. et al Choroidal neovascularization is provided by bone marrow cells.. Stem Cells 2004; 22: 21-6.
131 Pournaras CJ, Tsacopoulos M, Strommer K. et al. Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy.. Ophthalmology 1990; 97: 1321-8.
132 Pournaras CJ. Retinal oxygen distribution. Its role in the physiopathology of vasoproliferative microangiopathies.. Retina 1995; 15: 332-47.
133 Lopez-Barneo J, Pardal R, Ortega-Saenz P. Cellular mechanism of oxygen sensing.. Annu Rev Physiol 2001; 63: 259-87.
134 Wenger RH. Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression.. FASEB J 2002; 16: 1151-62.
135 van der Zee R, Murohara T, Luo Z. et al. Vascular endothelial growth factor/vascular permeability factor augments nitric oxide release from quiescent rabbit and human vascular endothelium.. Circulation 1997; 95: 1030-7.
136 Ashrafpour H, Huang N, Neligan PC. et al. Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature.. Am J Physiol Heart Circ Physiol 2004; 286: H946-54.
137 Penn JS, Rajaratnam VS. Inhibition of retinal neovascularization by intravitreal injection of human rPAI-1 in a rat model of retinopathy of prematurity.. Invest Ophthalmol Vis Sci 2003; 44: 5423-9.
138 Nase GP, Tuttle J, Bohlen HG. Reduced perivascular PO2 increases nitric oxide release from endothelial cells.. Am J Physiol Heart Circ Physiol 2003; 285: H507-15.
139 Naik JS, O'Donaughy TL, Walker BR. Endogenous carbon monoxide is an endothelial-derived vasodilator factor in the mesenteric circulation.. Am J Physiol Heart Circ Physiol 2003; 284: H838-45.
140 Michiels C, Minet E, Mottet D. et al. Regulation of gene expression by oxygen: NF-kappaB and HIF-1, two extremes.. Free Radic Biol Med 2002; 33: 1231-42.
141 Matsushita H, Morishita R, Nata T. et al. Hypoxia- induced endothelial apoptosis through nuclear factor- kappaB (NF-kappaB)-mediated bcl-2 suppression: in vivo evidence of the importance of NF-kappaB in endothelial cell regulation.. Circ Res 2000; 86: 974-81.
142 Iida T, Mine S, Fujimoto H. et al. Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells.. Genes Cells 2002; 7: 143-9.
143 Takahashi K, Kishi S, Muraoka K. et al. Reperfusion of occluded capillary beds in diabetic retinopathy.. Am J Ophthalmol 1998; 126: 791-7.
144 Cringle SJ, Yu DY, Yu PK. et al. Intraretinal oxygen consumption in the rat in vivo.. Invest Ophthalmol Vis Sci 2002; 43: 1922-7.
145 Pfefer TJ, Barton JK, Smithies DJ. et al. Modeling laser treatment of port wine stains with a computerreconstructed biopsy.. Lasers Surg Med 1999; 24: 151-66.
146 Blinc A, Kennedy SD, Bryant RG. et al. Flow through clots determines the rate and pattern of fibrinolysis.. Thromb Haemost 1994; 71: 230-5.
147 Komorowicz E, Kolev K, Lerant I. et al. Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases.. Circ Res 1998; 82: 1102-8.
148 Robinson BR, Houng AK, Reed GL. Catalytic life of activated factor XIII in thrombi: implications for fibrinolytic resistance and thrombus aging.. Circulation 2000; 102: 1151-7.
149 Yoshioka A, Fukutake K, Takamatsu J. et al. Clinical evaluation of a recombinant factor VIII preparation (Kogenate) in previously untreated patients with hemophilia A.. Int J Hematol 2003; 78: 467-74.
150 Hedner U. Recombinant factor VIIa (NovoSeven) as a hemostatic agent.. Semin Hematol 2001; 38 (Suppl. 12) 43-7.
151 Poon MC, d’Oiron R. Recombinant activated factor VII (NovoSeven) treatment of platelet-related bleeding disorders. International Registry on Recombinant Factor VIIa and Congenital Platelet Disorders Group.. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 01) S55-68.
152 Grounds M. Recombinant factor VIIa (rFVIIa) and its use in severe bleeding in surgery and trauma: a review.. Blood Rev 2003; 17 (Suppl. 01) S11-21.
153 Hoffman M, Monroe DM. The action of high dose factor VIIa (FVIIa) in a cell-based model of hemostasis.. Dis Mon 2003; 49: 14-21.
154 Tomokiyo K, Nakatomi Y, Araki T. et al. A novel therapeutic approach combining human plasma-derived Factors VIIa and X for haemophiliacs with inhibitors: evidence of a higher thrombin generation rate in vitro and more sustained haemostatic activity in vivo than obtained with Factor VIIa alone.. Vox Sang 2003; 85: 290-9.
155 Gootenberg JE. Factor concentrates for the treatment of factor XIII deficiency.. Curr Opin Hematol 1998; 5: 372-5.
156 Reed GL, Houng AK. The contribution of activated factor XIII to fibrinolytic resistance in experimental pulmonary embolism.. Circulation 1999; 99: 299-304.
157 Siebenlist KR, Mosesson MW. Progressive crosslinking of fibrin gamma chains increases resistance to fibrinolysis.. J Biol Chem 1994; 269: 28414-9.
158 Reed GL, Matsueda GR, Haber E. Platelet factor XIII increases the fibrinolytic resistance of plateletrich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin.. Thromb Haemost 1992; 68: 315-20.
159 Madison EL, Goldsmith EJ, Gerard RD. et al. Serpin-resistant mutants of human tissue-type plasminogen activator.. Nature 1989; 339: 721-4.
160 Huntington JA. Mechanisms of glycosaminoglycan activation of the serpins in hemostasis.. J Thromb Haemost 2003; 1: 1535-49.
161 Nesheim M. Thrombin and fibrinolysis.. Chest 2003; 124: 33S-9S.
162 Pieters J, Willems G, Hemker HC. et al. Inhibition of factor IXa and factor Xa by antithrombin III/ heparin during factor X activation.. J Biol Chem 1988; 263: 15313-8.
163 Pratt CW, Church FC. General features of the heparin- binding serpins antithrombin, heparin cofactor II and protein C inhibitor.. Blood Coagul Fibrinolysis 1993; 4: 479-90.
164 Hopkins PC, Pike RN, Stone SR. Evolution of serpin specificity: cooperative interactions in the reactive- site loop sequence of antithrombin specifically restrict the inhibition of activated protein C.. J Mol Evol 2000; 51: 507-15.
165 Gray E, Barrowcliffe TW. Inhibition of antithrombin III by lipid peroxides.. Thromb Res 1985; 37: 241-50.
166 Chamley LW, McKay EJ, Pattison NS. Inhibition of heparin/antithrombin III cofactor activity by anticardiolipin antibodies: a mechanism for thrombosis.. Thromb Res 1993; 71: 103-11.
167 Raja SM, Chhablani N, Swanson R. et al. Deletion of P1 arginine in a novel antithrombin variant (antithrombin London) abolishes inhibitory activity but enhances heparin affinity and is associated with early onset of thrombosis.. J Biol Chem 2003; 278: 13688-95.
168 Esmon CT. The protein C pathway.. Chest 2003; 124: 26S-32S.
169 Preissner KT, Muller-Berghaus G. Neutralization and binding of heparin by S protein/vitronectin in the inhibition of factor Xa by antithrombin III. Involvement of an inducible heparin-binding domain of S protein/ vitronectin.. J Biol Chem 1987; 262: 12247-53.
170 Kawata K, Takeyoshi I, Iwanami K. et al. The effects of a selective cyclooxygenase-2 inhibitor on small bowel ischemia-reperfusion injury.. Hepatogastroenterology 2003; 50: 1970-4.
171 West JL, Halas NJ. Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics.. Annu Rev Biomed Eng 2003; 5: 285-92.
172 Barratt G. Colloidal drug carriers: achievements and perspectives.. Cell Mol Life Sci 2003; 60: 21-37.
173 Sershen SR, Westcott SL, Halas NJ. et al. Temperature- sensitive polymer-nanoshell composites for photothermally modulated drug delivery.. J Biomed Mater Res 2000; 51: 293-8.
174 Scherer K, Lorenz S, Wimmershoff M. et al. Both the flashlamp-pumped dye laser and the longpulsed tunable dye laser can improve results in portwine stain therapy.. Br J Dermatol 2001; 145: 79-84.
175 Chang CJ, Kelly KM, van Gemert MJC. et al. Comparing the effectiveness of 585-nm vs. 595-nm wavelength pulsed dye laser treatment of port wine stains in conjunction with cryogen spray cooling.. Lasers Surg Med 2002; 31: 352-8.
176 Edström DW, Ros AM. The treatment of portwine stains with the pulsed dye laser at 600 nm.. Br J Dermatol 1997; 136: 360-3.
177 Rosenblum I W, Murata S, Nelson GH. et al. Anti-CD31 delays platelet adhesion/aggregation at sites of endothelial injury in mouse cerebral arterioles.. Am J Pathol 1994; 145: 33-6.
178 Rosenblum I W, Nelson GH, Wormley B. et al. Role of platelet-endothelial cell adhesion molecule (PECAM) in platelet adhesion/aggregation over injured but not denuded endothelium in vivo and ex vivo.. Stroke 1996; 27: 709-11.
179 Suthamjariya K, Farinelli WA, Koh W. et al. Mechanisms of microvascular response to laser pulses.. J Invest Dermatol 2004; 122: 518-25.
180 Newman PJ, Newman DK. Signal transduction pathways mediated by PECAM-1: new roles for an old molecule in platelet and vascular cell biology.. Arterioscler Thromb Vasc Biol 2003; 23: 953-64.
181 Jones KL, Hughan SC, Dopheide SM. et al. Platelet endothelial cell adhesion molecule-1 is a negative regulator of platelet-collagen interactions.. Blood 2001; 98: 1456-63.
182 Cicmil M, Thomas JM, Leduc M. et al. Platelet endothelial cell adhesion molecule-1 signaling inhibits the activation of human platelets.. Blood 2002; 99: 137-44.
183 Béguin S, Kumar R, Keularts I. et al. Fibrin-dependent platelet procoagulant activity requires GPIb receptors and von Willebrand factor.. Blood 1999; 93: 564-70.
184 Grunkemeier JM, Tsai WB, McFarland CD. et al. The effect of adsorbed fibrinogen, fibronectin, von Willebrand factor and vitronectin on the procoagulant state of adherent platelets.. Biomaterials 2000; 21: 2243-52.
185 Minamoto Y, Hato T, Nakatani S. et al. Detection of platelet adhesion/aggregation to immobilized ligands on microbeads by an aggregometer.. Thromb Haemost 1996; 76: 1072-9.
186 Mirshahi M, Soria J, Lu H. et al. Defective thrombolysis due to collagen incorporation in fibrin clots.. Thromb Res Suppl 1988; 8: 73-80.
187 Mirshahi M, Azzarone B, Soria J. et al. The role of fibroblasts in organization and degradation of a fibrin clot.. J Lab Clin Med 1991; 117: 274-81.
188 Hackam DJ, Ford HR. Cellullar, biochemical, and clinical aspects of wound healing.. Surg Infect 2002; 3 (Suppl. 01) Suppl S23-35.
189 Varma MR, Moaveni DM, Dewyer NA. et al. Deep vein thrombosis resolution is not accelerated with increased neovascularization.. J Vasc Surg 2004; 40: 536-42.
190 Henke PK, Varga A, De S. et al. Deep vein thrombosis resolution is modulated by monocyte CXCR2-mediated activity in a mouse model.. Arterioscler Thromb Vasc Biol 2004; 24: 1130-7.
191 Burnand KG, Gaffney PJ, McGuinness CL. et al. The role of the monocyte in the generation and dissolution of arterial and venous thrombi.. Cardiovasc Surg 1998; 6: 119-25.
192 Schafer K, Konstantinides S, Riedel C. et al. Different mechanisms of increased luminal stenosis after arterial injury in mice deficient for urokinase- or tissue- type plasminogen activator.. Circulation 2002; 106: 1847-52.
193 Northeast AD, Soo KS, Bobrow LG. et al. The tissue plasminogen activator and urokinase response in vivo during natural resolution of venous thrombus.. J Vasc Surg 1995; 22: 573-9.
194 Simon I D, Rao NK, Xu H. et al. Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells.. Blood 1996; 88: 3185-94.
195 Shi C, Zhang X, Chen Z. et al. Integrin engagement regulates monocyte differentiation through the forkhead transcription factor Foxp1.. J Clin Invest 2004; 114: 408-18.
196 Henke PK, Wakefield TW, Kadell AM. et al. Interleukin- 8 administration enhances venous thrombosis resolution in a rat model.. J Surg Res 2001; 99: 84-91.
197 Feigl W, Leu HJ, Lintner F. et al. New findings on angiogenesis within the scope of organization processes.. Vasa 1985; 14: 371-8.
198 Prathap K. Surface lining cells of healing thrombi in rat femoral veins: an electron-microscope study.. J Pathol 1972; 107: 1-8.
199 Sevitt S. The mechanisms of canalisation in deep vein thrombosis.. J Pathol 1973; 110: 153-65.
200 Stirling GA, Tsapogas MJ. In vitro culture of artificial thrombi.. Angiology 1969; 20: 44-51.
201 Tsapogas MJ, Stirling GA, Girolami PL. Study on the organization of experimental thrombi.. Angiology 1966; 17: 825-32.
202 Wiener J, Spiro D. Electron microscope studies in experimental thrombosis.. Exp Mol Pathol 1962; 1: 554-72.
203 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: 1202-12.
204 Young PP, Hofling AA, Sands MS. VEGF increases engraftment of bone marrow-derived endothelial progenitor cells (EPCs) into vasculature of newborn murine recipients.. Proc Natl Acad Sci U S A 2002; 99: 11951-6.
205 Csaky KG, Baffi JZ, Byrnes GA. et al. Recruitment of marrow-derived endothelial cells to experimental choroidal neovascularization by local expression of vascular endothelial growth factor.. Exp Eye Res 2004; 78: 1107-16.
206 Moore MA, Hattori K, Heissig B. et al. Mobilization of endothelial and hematopoietic stem and progenitor cells by adenovector-mediated elevation of serum levels of SDF-1, VEGF, and angiopoietin-1.. Ann N Y Acad Sci 2001; 938: 36-45.
207 Arisato T, Hashiguchi T, Sarker KP. et al. Highly accumulated platelet vascular endothelial growth factor in coagulant thrombotic region.. J Thromb Haemost 2003; 1: 2589-93.
208 Ceradini DJ, Kulkarni AR, Callaghan MJ. et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1.. Nat Med 2004; 10: 858-64.
209 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: 111-20.
210 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: 1322-8.
211 van Aken PJ, Emeis JJ. Organization of experimentally induced arterial thrombosis in rats: the first six days.. Artery 1982; 11: 156-73.
212 Deb A, Skelding KA, Wang S. et al Integrin profile and in vivo homing of human smooth muscle progenitor cells. Circulation 2004 [Epub ahead of print].
213 Hodivala-Dilke KM, Reynolds AR, Reynolds LE. Integrins in angiogenesis: multitalented molecules in a balancing act.. Cell Tissue Res 2003; 314: 131-44.
214 Schvartz I, Seger D, Maik-Rachline G. et al. Truncated vitronectins: binding to immobilized fibrin and to fibrin clots, and their subsequent interaction with cells.. Biochem Biophys Res Commun 2002; 290: 682-9.
215 Ruoslahti E. RGD and other recognition sequences for integrins.. Annu Rev Cell Dev Biol 1996; 12: 697-715.
216 Wijelath ES, Rahman S, Murray J. et al. Fibronectin promotes VEGF-induced CD34 cell differentiation into endothelial cells.. J Vasc Surg 2004; 39: 655-60.
217 Sasaki T, Timpl R. Domain IVa of laminin alpha5 chain is cell-adhesive and binds beta1 and alphaVbeta3 integrins through Arg-Gly-Asp.. FEBS Lett 2001; 509: 181-5.
218 Asosingh K, Renmans W, Van der Gucht K. et al. Circulating CD34+ cells in cord blood and mobilized blood have a different profile of adhesion molecules than bone marrow CD34+ cells.. Eur J Haematol 1998; 60: 153-60.
219 Liu ZJ, Snyder R, Soma A. et al. VEGF-A and alphaVbeta3 integrin synergistically rescue angiogenesis via N-Ras and PI3-K signaling in human microvascular endothelial cells.. FASEB J 2003; 17: 1931-3.
220 Manalo DJ, Rowan A, Lavoie T. et al. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood 2004 [Epub ahead of print].
221 Espinosa-Heidmann DG, Caicedo A, Hernandez EP. et al. Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization.. Invest Ophthalmol Vis Sci 2003; 44: 4914-9.
222 Barsky SH, Rosen S, Geer DE. et al. The nature and evolution of port wine stains: a computer-assisted study.. J Invest Dermatol 1980; 74: 154-7.
223 Smithies DJ, van Gemert MJ, Hansen MK. et al. Three-dimensional reconstruction of port wine stain vascular anatomy from serial histological sections.. Phys Med Biol 1997; 42: 1843-7.
224 Rydh M, Malm M, Jernbeck J. et al. Ectatic blood vessels in port-wine stains lack innervation: possible role in pathogenesis.. Plast Reconstr Surg 1991; 87: 419-22.
225 Laube S, Taibjee S, Lanigan SW. Treatment of resistant port wine stains with the V Beam pulsed dye laser.. Lasers Surg Med 2003; 33: 282-7.
226 Yan SF, Mackman N, Kisiel W. et al. Hypoxia/hypoxemia- induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis.. Arterioscler Thromb Vasc Biol 1999; 19: 2029-35.
227 Pinsky DJ, Naka Y, Liao H. et al. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation.. J Clin Invest 1996; 97: 493-500.
228 Underiner TL, Ruggeri B, Gingrich DE. Development of vascular endothelial growth factor receptor (VEGFR) kinase inhibitors as anti-angiogenic agents in cancer therapy.. Curr Med Chem 2004; 11: 731-45.
229 Zilberberg L, Shinkaruk S, Lequin O. et al. Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor.. J Biol Chem 2003; 278: 35564-73.
230 Manley PW, Bold G, Bruggen J. et al. Advances in the structural biology, design and clinical development of VEGF-R kinase inhibitors for the treatment of angiogenesis.. Biochim Biophys Acta 2004; 1697: 17-27.
231 Mezquita J, Mezquita B, Pau M. et al. Downregulation of Flt-1 gene expression by the proteasome inhibitor MG262.. J Cell Biochem 2003; 89: 1138-47.
232 Roberts WG, Palade GE. Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor.. J Cell Sci 1995; 108: 2369-79.
233 Prager GW, Breuss JM, Steurer S. et al. Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells.. Blood 2004; 103: 955-62.
234 Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells.. J Biol Chem 1998; 273: 13313-6.
235 Gerber HP, Malik AK, Solar GP. et al. VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism.. Nature 2002; 417: 954-8.
236 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: 1194-201.