Abstract
The isolation of endothelial progenitor cells (EPCs) derived from adult bone marrow (BM) was an epoch-making event for the recognition of “neovessel formation” occurring as physiological and pathological responses in adults. The finding that EPCs home to sites of neovascularization and differentiate into endothelial cells (ECs) in situ is consistent with “vasculogenesis,” a critical paradigm well described for embryonic neovascularization, but proposed recently in adults, in which a reservoir of stem or progenitor cells contributes to vascular organogenesis. EPCs have also been considered as therapeutic agents to supply the potent origin of neovascularization under pathological conditions. Considering the regenerative implications, gene modification of stem cells has advantages over conventional gene therapy. Ex vivo gene transfection of stem cells may avoid administration of vectors and vehicles into the recipient organism. Stem cells isolated from adults may exhibit age-related, genetic, or acquired disease-related impairment of their regenerative ability. Transcriptional or enzymatic gene modification may constitute an effective means to maintain, enhance, or inhibit EPCs’ capacity to proliferate or differentiate. This chapter provides an update of EPC biology as well as EPCs’ potential use for therapeutic regeneration.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
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 275:964–967
Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearney M, Magner M, Isner JM (1999a) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228
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 18:3964–3972
Bhattacharya V, McSweeney P, Shi Q, Bruno B, Ishida A, Nash R, Storb R, Sauvage L, Hammond W, Wu M (2000) Enhanced endothelialization and microvessel formation in polyester graft seeded with CD34+ bone marrow cells. Blood 95:581–585
Boyer M, Townsend L, Vogel L, Falk J, Reitz-Vick D, Trevor K, Villalba M, Bendick P, Glover J (2000) Isolation of endothelial cells and their progenitor cells from human peripheral blood. J Vasc Surg 31:181–189
Choi K, Kennedy M, Kazarov A, Papadimitriou J, Keller G (1998) A common precursor for hematopoietic and endothelial cells. Development 125:725–732
Cowan KH, Moscow JA, Huang H, Zujewski JA, O’Shaughnessy J, Sorrentino B, Hines K, Carter D, Schneider E, Cusack G, Noone M, Dunbar C, Steinberg S, Wilson W, Goldspiel B, Read EJ, Leitman SF, McDonagh K, Chow C, Abati A, Chiang Y, Chang YN, Gottesman MM, Pastan I (1999) Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients. Clin Cancer Res 5:1619–1628
Crisa L, Cirulli V, Smith K, Ellisman M, Torbett B, Salomon D (1999) Human cord blood progenitors sustain thymic T-cell development and a novel form of angiogenesis. Blood 94:3928–3940
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 87:728–730
Dunbar CE, Kohn DB, Schiffmann R, Barton NW, Nolta JA, Esplin JA, Pensiero M, Long Z, Lockey C, Emmons RV, Csik S, Leitman S, Krebs CB, Carter C, Brady RO, Karlsson S (1998) Retroviral transfer of the glucocerebrosidase gene into CD34+ cells from patients with Gaucher disease: in vivo detection of transduced cells without myeloablation. Hum Gene Ther 9:2629–2640
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 65:287–300
Flamme I, Risau W (1992) Induction of vasculogenesis and hematopoiesis in vitro. Development 116:435–439
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 95:3106–3112
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 88:167–174
Gunsilius E, Duba HC, Petzer AL, Kahler CM, Grunewald K, Stockha 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 355:1688–1691
Harraz M, Jiao C, Hanlon HD, Hartley RS, Schatteman GC (2001) CD34− blood-derived human endothelial cell progenitors. Stem Cells 19:304–312
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 105:732–738
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 113:1311–1325
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 97:3422–3427
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 113:962–969
Karlsson S (1991) Treatment of genetic defects in hematopoietic cell function by gene transfer. Blood 78:2481–2492
Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, Rabkin E, Moran AM, Schoen FJ, Atala A, Soker S, Bischoff J, Mayer JE Jr (2001) Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 7:1035–1040
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 103:634–637
Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkoff 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 7:430–436
Levenberg S, Golub JS, Amit M, Itskovitz-Eldor J, Langer R (2002) Endothelial cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 99:4391–4396
Lin Y, Weisdorf D, Solovey A, Hebbel R (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105:71–77
Murasawa S, Llevadot J, Silver M, Isner JM, Losordo DW, Asahara T (2002) Constitutive human telomerase reverse transcriptase expression enhances regenerative properties of endothelial progenitor cells. Circulation 106:1133–1139
Murayama T, Tepper OM, Silver M, Ma H, Losordo D, 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 30:967
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 105:1527–1536
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 98:775–777
Pardanaud L, Altmann C, Kitos P, Dieterlen-Lievre F, Buck CA (1987) Vasculogenesis in the early quail blastodisc as studied with a monoclonal antibody recognizing endothelial cells. Development 100:339–349
Peichev M, Naiyer AJ, Pereira D, Ahu Z, Lane WJ, Williams M, Oz MC, Hicklin DJ, Witte L, Moore MAS (2000) Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors. Blood 95:952–958
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 115:186–194
Reisner Y, Segall H (1995) Hematopoietic stem cell transplantation for cancer therapy. Curr Opin Immunol 7:687–693
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 109:337–346
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 102:471–478
Schatteman GC, Hanlon HD, Jiao C, Dodds SG, Christy BA (2000) Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice. J Clin Invest 106:571–578
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 92:362–367
Shimizu T, Yamato M, Akutsu T, Shibata T, Isoi Y, Kikuchi A, Umezu M, Okano T (2002a) Electrically communicating three-dimensional cardiac tissue mimic fabricated by layered cultured cardiomyocyte sheets. J Biomed Mater Res 60:110–117
Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, Kikuchi A, Umezu M, Okano T (2002b) Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res 90:e40
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 103:2776–2779
Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M, Magner M, Isner J, Asahara T (1999) Ischemia-and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med 4:434–438
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 157:571–577
Weiss M, Orkin SH (1996) In vitro differentiation of murine embryonic stem cells: new approaches to old problems. J Clin Invest 97:591–595
Wong-Staal F, Poeschla EM, Looney DJ (1998) A controlled phase 1 clinical trial to evaluate the safety and effects in HIV-1 infected humans of autologous lymphocytes transduced with a ribozyme that cleaves HIV-1 RNA. Hum Gene Ther 9:2407–2425
Yin A, Miraglia S, Zanjani E, Almeida-Porada G, Ogawa M, Leary A, Olweus J, Kearney J, Buck D (1997) AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 90:5002–5012
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Asahara, T. (2007). Cell Therapy and Gene Therapy Using Endothelial Progenitor Cells for Vascular Regeneration. In: Kauser, K., Zeiher, AM. (eds) Bone Marrow-Derived Progenitors. Handbook of Experimental Pharmacology, vol 180. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68976-8_8
Download citation
DOI: https://doi.org/10.1007/978-3-540-68976-8_8
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-68975-1
Online ISBN: 978-3-540-68976-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)