Abstract
Since the discovery of circulating endothelial progenitor cells (EPC) in adult human peripheral blood, EPCs are believed to home to sites of neovascularization, where they contribute to vascular regeneration by forming a structural component of capillaries and by secreting angiogenic factors, thereby enhancing vascular and blood flow recovery in ischemic tissue. This therapeutic strategy has been effective in animal models of ischemia, and we and other clinical trials have demonstrated that it was safe and feasible for treatment of critical ischemic limb and cardiovascular diseases. However, the decline of EPCs in the peripheral blood and evidence that several disease states reduced EPC number and/or function have prompted the development of several strategies to overcome these limitations, including the administration of genetically modified EPCs that overexpress angiogenic growth factors. To optimize therapeutic outcomes, investigators must keep refining methods of EPC purification, expansion, and administration, and to develop techniques that overcome the intrinsic decline and phenotypic deficiencies of EPCs. In this chapter, we have illustrated EPC biology and the therapeutic potential of EPCs for vascular regeneration demonstrating our data of clinical study.
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References
Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275(5302):964–967
Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999a) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85(3):221–228
Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999b) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18(14):3964–3972. doi:10.1093/emboj/18.14.3964
Asahara T, Kawamoto A, Masuda H (2011) Concise review: circulating endothelial progenitor cells for vascular medicine. Stem Cells 29(11):1650–1655. doi:10.1002/stem.745
Boyer M, Townsend LE, Vogel LM, Falk J, Reitz-Vick D, Trevor KT, Villalba M, Bendick PJ, Glover JL (2000) Isolation of endothelial cells and their progenitor cells from human peripheral blood. J Vasc Surg 31(1 Pt 1):181–189. doi:S0741521400696751 [pii]
Burt RK, Testori A, Oyama Y, Rodriguez HE, Yaung K, Villa M, Bucha JM, Milanetti F, Sheehan J, Rajamannan N, Pearce WH (2010) Autologous peripheral blood CD133+ cell implantation for limb salvage in patients with critical limb ischemia. Bone Marrow Transplant 45(1):111–116. doi:bmt2009102 [pii] 10.1038/bmt.2009.102
Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 380(6573):435–439
Cho HJ, Youn SW, Cheon SI, Kim TY, Hur J, Zhang SY, Lee SP, Park KW, Lee MM, Choi YS, Park YB, Kim HS (2005) Regulation of endothelial cell and endothelial progenitor cell survival and vasculogenesis by integrin-linked kinase. Arterioscler Thromb Vasc Biol 25(6):1154–1160. doi:01.ATV.0000164312.20008.93 [pii] 10.1161/01.ATV.0000164312.20008.93
Choi K, Kennedy M, Kazarov A, Papadimitriou JC, Keller G (1998) A common precursor for hematopoietic and endothelial cells. Development 125(4):725–732
Crisa L, Cirulli V, Smith KA, Ellisman MH, Torbett BE, Salomon DR (1999) Human cord blood progenitors sustain thymic T-cell development and a novel form of angiogenesis. Blood 94(11):3928–3940
Crosby JR, Kaminski WE, Schatteman G, Martin PJ, Raines EW, Seifert RA, Bowen-Pope DF (2000) Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. Circ Res 87(9):728–730
Diller GP, van Eijl S, Okonko DO, Howard LS, Ali O, Thum T, Wort SJ, Bedard E, Gibbs JS, Bauersachs J, Hobbs AJ, Wilkins MR, Gatzoulis MA, Wharton J (2008) Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation 117(23):3020–3030. doi:CIRCULATIONAHA.108.769646 [pii] 10.1161/CIRCULATIONAHA.108.769646
Dimmeler S, Aicher A, Vasa M, Mildner-Rihm C, Adler K, Tiemann M, Rutten H, Fichtlscherer S, Martin H, Zeiher AM (2001) HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 108(3):391–397. doi:10.1172/JCI13152
Fernandez Pujol B, Lucibello FC, Gehling UM, Lindemann K, Weidner N, Zuzarte ML, Adamkiewicz J, Elsasser HP, Muller R, Havemann K (2000) Endothelial-like cells derived from human CD14 positive monocytes. Differentiation 65(5):287–300
Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380(6573):439–442
Folkman J, Shing Y (1992) Angiogenesis. J Biol Chem 267:10931–10934
Gehling UM, Ergun S, Schumacher U, Wagener C, Pantel K, Otte M, Schuch G, Schafhausen P, Mende T, Kilic N, Kluge K, Schafer B, Hossfeld DK, Fiedler W (2000) In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 95(10):3106–3112
Gill M, Dias S, Hattori K, Rivera ML, Hicklin D, Witte L, Girardi L, Yurt R, Himel H, Rafii S (2001) Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 88(2):167–174
Griese DP, Achatz S, Batzlsperger CA, Strauch UG, Grumbeck B, Weil J, Riegger GA (2003) Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells. Cardiovasc Res 58(2):469–477. doi:S0008636303002669 [pii]
Grzelak I, Olszewski WL, Zaleska M, Ziolkowska A, Durlik M, Lagiewska B, Muszynski M, Rowinski W (1998) Surgical trauma evokes a rise in the frequency of hematopoietic progenitor cells and cytokine levels in blood circulation. Eur Surg Res 30(3):198–204
Gunsilius E, Duba HC, Petzer AL, Kahler CM, Grunewald K, Stockhammer G, Gabl C, Dirnhofer S, Clausen J, Gastl G (2000) Evidence from a leukaemia model for maintenance of vascular endothelium by bone-marrow-derived endothelial cells. Lancet 355(9216):1688–1691. doi:S0140-6736(00)02241-8 [pii] 10.1016/S0140-6736(00)02241-8
Harraz M, Jiao C, Hanlon HD, Hartley RS, Schatteman GC (2001) CD34- blood-derived human endothelial cell progenitors. Stem Cells 19(4):304–312
Hattori K, Heissig B, Wu Y, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hackett NR, Crystal RG, Moore MA, Werb Z, Lyden D, Rafii S (2002) Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1(+) stem cells from bone-marrow microenvironment. Nat Med 8(8):841–849. doi:10.1038/nm740
Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S (2003) Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood 102(4):1340–1346. doi:10.1182/blood-2003-01-0223 2003-01-0223 [pii]
Heiss C, Keymel S, Niesler U, Ziemann J, Kelm M, Kalka C (2005) Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 45(9):1441–1448. doi:S0735-1097(05)7-8 [pii] 10.1016/j.jacc.2004.12.074
Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348(7):593–600. doi:10.1056/NEJMoa022287 348/7/593 [pii]
Ii M, Nishimura H, Iwakura A, Wecker A, Eaton E, Asahara T, Losordo DW (2005) Endothelial progenitor cells are rapidly recruited to myocardium and mediate protective effect of ischemic preconditioning via “imported” nitric oxide synthase activity. Circulation 111(9):1114–1120. doi:01.CIR.0000157144.24888.7E [pii] 10.1161/01.CIR.0000157144.24888.7E
Ii M, Takenaka H, Asai J, Ibusuki K, Mizukami Y, Maruyama K, Yoon YS, Wecker A, Luedemann C, Eaton E, Silver M, Thorne T, Losordo DW (2006) Endothelial progenitor thrombospondin-1 mediates diabetes-induced delay in reendothelialization following arterial injury. Circ Res 98(5):697–704. doi:01.RES.0000209948.50943.ea [pii] 10.1161/01.RES.0000209948.50943.ea
Imanishi T, Moriwaki C, Hano T, Nishio I (2005) Endothelial progenitor cell senescence is accelerated in both experimental hypertensive rats and patients with essential hypertension. J Hypertens 23(10):1831–1837. doi:00004872-200510000-00014 [pii]
Iwaguro H, Yamaguchi J, Kalka C, Murasawa S, Masuda H, Hayashi S, Silver M, Li T, Isner JM, Asahara T (2002) Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration. Circulation 105(6):732–738
Iwakura A, Luedemann C, Shastry S, Hanley A, Kearney M, Aikawa R, Isner JM, Asahara T, Losordo DW (2003) Estrogen-mediated, endothelial nitric oxide synthase-dependent mobilization of bone marrow-derived endothelial progenitor cells contributes to reendothelialization after arterial injury. Circulation 108(25):3115–3121. doi:10.1161/01.CIR.0000106906.56972.83 01.CIR.0000106906.56972.83 [pii]
Iwasaki H, Kawamoto A, Ishikawa M, Oyamada A, Nakamori S, Nishimura H, Sadamoto K, Horii M, Matsumoto T, Murasawa S, Shibata T, Suehiro S, Asahara T (2006) Dose-dependent contribution of CD34-positive cell transplantation to concurrent vasculogenesis and cardiomyogenesis for functional regenerative recovery after myocardial infarction. Circulation 113(10):1311–1325
Kalka C, Masuda H, Takahashi T, Kalka-Moll WM, Silver M, Kearney M, Li T, Isner JM, Asahara T (2000) Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA 97(7):3422–3427. doi:10.1073/pnas.070046397070046397 [pii]
Kamei N, Kwon SM, Alev C, Ishikawa M, Yokoyama A, Nakanishi K, Yamada K, Horii M, Nishimura H, Takaki S, Kawamoto A, Ii M, Akimaru H, Tanaka N, Nishikawa S, Ochi M, Asahara T (2010) Lnk deletion reinforces the function of bone marrow progenitors in promoting neovascularization and astrogliosis following spinal cord injury. Stem Cells 28(2):365–375. doi:10.1002/stem.243
Kang HJ, Kim SC, Kim YJ, Kim CW, Kim JG, Ahn HS, Park SI, Jung MH, Choi BC, Kimm K (2001) Short-term phytohaemagglutinin-activated mononuclear cells induce endothelial progenitor cells from cord blood CD34+ cells. Br J Haematol 113(4):962–969. doi:bjh2694 [pii]
Kawamoto A, Gwon HC, Iwaguro H, Yamaguchi JI, Uchida S, Masuda H, Silver M, Ma H, Kearney M, Isner JM, Asahara T (2001) Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia. Circulation 103(5):634–637
Kawamoto A, Murayama T, Kusano K, Ii M, Tkebuchava T, Shintani S, Iwakura A, Johnson I, von Samson P, Hanley A, Gavin M, Curry C, Silver M, Ma H, Kearney M, Losordo DW (2004) Synergistic effect of bone marrow mobilization and vascular endothelial growth factor-2 gene therapy in myocardial ischemia. Circulation 110(11):1398–1405. doi:10.1161/01.CIR.0000141563.71410.64 01.CIR.0000141563.71410.64 [pii]
Kawamoto A, Katayama M, Handa N, Kinoshita M, Takano H, Horii M, Sadamoto K, Yokoyama A, Yamanaka T, Onodera R, Kuroda A, Baba R, Kaneko Y, Tsukie T, Kurimoto Y, Okada Y, Kihara Y, Morioka S, Fukushima M, Asahara T (2009) Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial. Stem Cells 27(11):2857–2864. doi:10.1002/stem.207
Kermani P, Rafii D, Jin DK, Whitlock P, Schaffer W, Chiang A, Vincent L, Friedrich M, Shido K, Hackett NR, Crystal RG, Rafii S, Hempstead BL (2005) Neurotrophins promote revascularization by local recruitment of TrkB + endothelial cells and systemic mobilization of hematopoietic progenitors. J Clin Invest 115(3):653–663
Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7(4):430–436. doi:10.1038/86498 86498 [pii]
Kondo T, Hayashi M, Takeshita K, Numaguchi Y, Kobayashi K, Iino S, Inden Y, Murohara T (2004) Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler Thromb Vasc Biol 24(8):1442–1447. doi:10.1161/01.ATV.0000135655.52088.c5 01.ATV.0000135655.52088.c5 [pii]
Kong D, Melo LG, Gnecchi M, Zhang L, Mostoslavsky G, Liew CC, Pratt RE, Dzau VJ (2004) Cytokine-induced mobilization of circulating endothelial progenitor cells enhances repair of injured arteries. Circulation 110(14):2039–2046. doi:10.1161/01.CIR.0000143161.01901.BD 01.CIR.0000143161.01901.BD [pii]
Kureishi Y, Luo Z, Shiojima I, Bialik A, Fulton D, Lefer DJ, Sessa WC, Walsh K (2000) The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med 6(9):1004–1010
Kwon SM, Eguchi M, Wada M, Iwami Y, Hozumi K, Iwaguro H, Masuda H, Kawamoto A, Asahara T (2008) Specific Jagged-1 signal from bone marrow microenvironment is required for endothelial progenitor cell development for neovascularization. Circulation 118(2):157–165. doi:10.1161/CIRCULATIONAHA.107.754978 CIRCULATIONAHA.107.754978 [pii]
Lev EI, Kleiman NS, Birnbaum Y, Harris D, Korbling M, Estrov Z (2005) Circulating endothelial progenitor cells and coronary collaterals in patients with non-ST segment elevation myocardial infarction. J Vasc Res 42(5):408–414. doi:JVR2005042005408 [pii] 10.1159/000087370
Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R (2002) Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci USA 99(7):4391–4396
Li X, Tjwa M, Moons L, Fons P, Noel A, Ny A, Zhou JM, Lennartsson J, Li H, Luttun A, Ponten A, Devy L, Bouche A, Oh H, Manderveld A, Blacher S, Communi D, Savi P, Bono F, Dewerchin M, Foidart JM, Autiero M, Herbert JM, Collen D, Heldin CH, Eriksson U, Carmeliet P (2005) Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors. J Clin Invest 115(1):118–127. doi:10.1172/JCI19189
Lin Y, Weisdorf DJ, Solovey A, Hebbel RP (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105(1):71–77
Llevadot J, Murasawa S, Kureishi Y, Uchida S, Masuda H, Kawamoto A, Walsh K, Isner JM, Asahara T (2001) HMG-CoA reductase inhibitor mobilizes bone marrow–derived endothelial progenitor cells. J Clin Invest 108(3):399–405. doi:10.1172/JCI13131
Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Traverse JH, Amrani D, Ewenstein BM, Riedel N, Story K, Barker K, Povsic TJ, Harrington RA, Schatz RA (2011) Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res 109(4):428–436. doi:CIRCRESAHA.111.245993 [pii] 10.1161/CIRCRESAHA.111.245993
Masuda H, Alev C, Akimaru H, Ito R, Shizuno T, Kobori M, Horii M, Ishihara T, Isobe K, Isozaki M, Itoh J, Itoh Y, Okada Y, McIntyre BA, Kato S, Asahara T (2011) Methodological development of a clonogenic assay to determine endothelial progenitor cell potential. Circ Res 109(1):20–37. doi:10.1161/CIRCRESAHA.110.231837
Michaud SE, Dussault S, Haddad P, Groleau J, Rivard A (2006) Circulating endothelial progenitor cells from healthy smokers exhibit impaired functional activities. Atherosclerosis 187(2):423–432
Moore MA, Hattori K, Heissig B, Shieh JH, Dias S, Crystal RG, Rafii S (2001) 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 938:36–45; discussion 45–37
Murayama T, Tepper OM, Silver M, Ma H, Losordo DW, Isner JM, Asahara T, Kalka C (2002) Determination of bone marrow-derived endothelial progenitor cell significance in angiogenic growth factor-induced neovascularization in vivo. Exp Hematol 30(8):967–972. doi:S0301472X02008676 [pii]
Murohara T, Ikeda H, Duan J, Shintani S, Sasaki K, Eguchi H, Onitsuka I, Matsui K, Imaizumi T (2000) Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization. J Clin Invest 105(11):1527–1536. doi:10.1172/JCI8296
Nagaya N, Kangawa K, Kanda M, Uematsu M, Horio T, Fukuyama N, Hino J, Harada-Shiba M, Okumura H, Tabata Y, Mochizuki N, Chiba Y, Nishioka K, Miyatake K, Asahara T, Hara H, Mori H (2003) Hybrid cell-gene therapy for pulmonary hypertension based on phagocytosing action of endothelial progenitor cells. Circulation 108(7):889–895. doi:10.1161/01.CIR.0000079161.56080.22 01.CIR.0000079161.56080.22 [pii]
Nieda M, Nicol A, Denning-Kendall P, Sweetenham J, Bradley B, Hows J (1997) Endothelial cell precursors are normal components of human umbilical cord blood. Br J Haematol 98(3):775–777
Peichev M, Naiyer AJ, Pereira D, Zhu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MA, Rafii S (2000) Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood 95(3):952–958
Quirici N, Soligo D, Caneva L, Servida F, Bossolasco P, Deliliers GL (2001) Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. Br J Haematol 115(1):186–194. doi:3077 [pii]
Reyes M, Dudek A, Jahagirdar B, Koodie L, Marker PH, Verfaillie CM (2002) Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109(3):337–346. doi:10.1172/JCI14327
Risau W, Flamme I (1995) Vasculogenesis. Annu Rev Cell Dev Biol 11:73–91
Risau W, Sariola H, Zerwes HG, Sasse J, Ekblom P, Kemler R, Doetschman T (1988) Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development 102(3):471–478
Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA (2000) Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest 106(4):571–578. doi:10.1172/JCI9087
Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, Dimmeler S, Zeiher AM (2005) Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 111(22):2981–2987. doi:CIRCULATIONAHA.104.504340 [pii] 10.1161/CIRCULATIONAHA.104.504340
Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376(6535):62–66
Shi Q, Rafii S, Wu MH, Wijelath ES, Yu C, Ishida A, Fujita Y, Kothari S, Mohle R, Sauvage LR, Moore MA, Storb RF, Hammond WP (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92(2):362–367
Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shimada T, Oike Y, Imaizumi T (2001) Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation 103(23):2776–2779
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner JM, Asahara T (1999) Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 5(4):434–438. doi:10.1038/7434
Tamaki T, Akatsuka A, Ando K, Nakamura Y, Matsuzawa H, Hotta T, Roy RR, Edgerton VR (2002) Identification of myogenic-endothelial progenitor cells in the interstitial spaces of skeletal muscle. J Cell Biol 157(4):571–577. doi:10.1083/jcb.200112106 jcb.200112106 [pii]
Tanaka R, Wada M, Kwon SM, Masuda H, Carr J, Ito R, Miyasaka M, Warren SM, Asahara T, Tepper OM (2008) The effects of flap ischemia on normal and diabetic progenitor cell function. Plast Reconstr Surg 121(6):1929–1942. doi:10.1097/PRS.0b013e3181715218 00006534-200806000-00007 [pii]
Urbich C, Dernbach E, Zeiher AM, Dimmeler S (2002) Double-edged role of statins in angiogenesis signaling. Circ Res 90(6):737–744
Valgimigli M, Rigolin GM, Fucili A, Porta MD, Soukhomovskaia O, Malagutti P, Bugli AM, Bragotti LZ, Francolini G, Mauro E, Castoldi G, Ferrari R (2004) CD34+ and endothelial progenitor cells in patients with various degrees of congestive heart failure. Circulation 110(10):1209–1212. doi10.1161/01.CIR.0000136813.89036.21 01.CIR.0000136813.89036.21 [pii]
Vasa M, Fichtlscherer S, Adler K, Aicher A, Martin H, Zeiher AM, Dimmeler S (2001a) Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 103(24):2885–2890
Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001b) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89(1):E1–E7
Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353(10):999–1007. doi:353/10/999 [pii] 10.1056/NEJMoa043814
Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, Olweus J, Kearney J, Buck DW (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90(12):5002–5012
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Ii, M., Kawamoto, A., Asahara, T. (2013). Vascular Regeneration: Endothelial Progenitor Cell Therapy for Ischemic Diseases. In: Steinhoff, G. (eds) Regenerative Medicine. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5690-8_35
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