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Ischemic Tissue Repair by Autologous Bone Marrow-Derived Stem Cells: Scientific Basis and Preclinical Data

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Bone Marrow-Derived Progenitors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 180))

Abstract

The success of therapies targeting acute myocardial ischemia and the aging of the population due to improved general medical care has resulted in an increasing population of patients with chronic myocardial ischemia and congestive heart failure who remain symptomatic despite having exhausted the currently available therapeutic options. In this chapter we review the scientific underpinnings of autologous bone marrow-derived cell therapy and the early clinical experience that has fuelled interest in this approach.

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References

  • Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Theme H, Iwamoto MA, Parke JE, Nguyen MD, Aiello LM, Ferrara N, King GL (1994) Vascular endothelial growth factor in ocular fluids of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Asahara T, Masuda H, Takahashi T, Kalka C, Pastore C, Silver M, Kearne M, Magner M, Isner JM (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 85:221–228

    PubMed  CAS  Google Scholar 

  • Baumgartner I, Rauh G, Pieczek A, Wuensch D, Magner M, Kearney M, Schainfeld R, Isner JM (2000) Lower-extremity edema associated with gene transfer of naked DNA vascular endothelial growth factor. Ann Intern Med 132:880–884

    PubMed  CAS  Google Scholar 

  • Campbell WB, Johnston JA, Kernick VF, Rutter EA (1994) Lower limb amputation: striking the balance. Ann R Coll Surg Engl 76:205–209

    PubMed  CAS  Google Scholar 

  • Dawson I, Keller BP, Brand R, Pesch-Batenburg J, Hajo van Bockel J (1995) Late outcomes of limb loss after failed infrainguinal bypass. J Vasc Surg 21:613–622

    Article  PubMed  CAS  Google Scholar 

  • 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 108:391–397

    Article  PubMed  CAS  Google Scholar 

  • Eneroth M, Persson BM (1992) Amputation for occlusive arterial disease. A multicenter study of 177 amputees. Int Orthop 16:382–387

    Article  Google Scholar 

  • Flamme I, Risau W (1992) Induction of vasculogenesis and hematopoiesis in vitro. Development 116:435–439

    PubMed  CAS  Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  PubMed  CAS  Google Scholar 

  • Fuchs S, Baffour R, Zhou YF, Shou M, Pierre A, Tio FO, Weissman NJ, Leon MB, Epstein SE, Kornowski R (2001) Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. J Am Coll Cardiol 37:1726–1732

    Article  PubMed  CAS  Google Scholar 

  • Gilbert SF (1997) Developmental biology, fourth edn. Sinauer Associates, Sunderland

    Google Scholar 

  • Hamano K, Nishida M, Hirata K, Mikamo A, Li TS, Harada M, Miura T, Matsuzaki M, Esato K (2001) Local implantation of autologous bone marrow cells for therapeutic angiogenesis in patients with ischemic heart disease: clinical trials and preliminary results. Jpn Circ J 65:845–847

    Article  PubMed  CAS  Google Scholar 

  • Hariawala MD, Horowitz JR, Esakof D, Sheriff DD, Walter DH, Keyt B, Isner JM, Symes JF (1996) VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts. J Surg Res 63:77–82

    Article  PubMed  CAS  Google Scholar 

  • Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    Article  PubMed  CAS  Google Scholar 

  • Harrington L, Zhou W, McPhail T, Oulton R, Yeung DS, Mar V, Bass MB, Robinson MO (1997) Human telomerase contains evolutionarily conserved catalytic and structural subunits. Genes Dev 11:3109–3115

    PubMed  CAS  Google Scholar 

  • Hastie ND, Dempster M, Dunlop MG, Thompson AM, Green DK, Allshire RC (1990) Telomere reduction in human colorectal carcinoma and with ageing. Nature 346:866–868

    Article  PubMed  CAS  Google Scholar 

  • Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh JH, Hackett NR, Quitoriano MS, Crystal RG, Rafii S, Moore MA (2001) Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood 97:3354–3360

    Article  PubMed  CAS  Google Scholar 

  • 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 348:593–600

    Article  PubMed  Google Scholar 

  • Horowitz JR, Rivard A, van der Zee R, Hariawala MD, Sheriff DD, Esakof DD, Chaudhry M, Symes JF, Isner JM (1997) Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Arterioscler Thromb Vasc Biol 17:2793–2800

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kamihata H, Matsubara H, Nishiue T, Fujiyama S, Tsutsumi Y, Ozono R, Masaki H, Mori Y, Iba O, Tateishi E, Kosaki A, Shintani S, Murohara T, Imaizumi T, Iwasaka T (2001) Implantation of bone marrow mononuclear cells into ischemic myocardium enhances collateral perfusion and regional function via side supply of angioblasts, angiogenic ligands, and cytokines. Circulation 104:1046–1052

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Kawamoto A, Tkebuchava T, Yamaguchi J, Nishimura H, Yoon YS, Milliken C, Uchida S, Masuo O, Iwaguro H, Ma H, Hanley A, Silver M, Kearney M, Losordo DW, Isner JM, Asahara T (2003) Intramyocardial transplantation of autologous endothelial progenitor cells for therapeutic neovascularization of myocardial ischemia. Circulation 107:461–468

    Article  PubMed  Google Scholar 

  • Kilian A, Bowtell DD, Abud HE, Hime GR, Venter DJ, Keese PK, Duncan EL, Reddel RR, Jefferson RA (1997) Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types. Hum Mol Genet 6:2011–2019

    Article  PubMed  CAS  Google Scholar 

  • 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 7:430–436

    Article  PubMed  CAS  Google Scholar 

  • Lataillade JJ, Clay D, Dupuy C, Rigal S, Jasmin C, Bourin P, Le Bousse-Kerdiles MC (2000) Chemokine SDF-1 enhances circulating CD34(+) cell proliferation in synergy with cytokines: possible role in progenitor survival. Blood 95:756–768

    PubMed  CAS  Google Scholar 

  • Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, Dzau VJ (2003) Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9:1195–1201

    Article  PubMed  CAS  Google Scholar 

  • Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, Caddle SD, Ziaugra L, Beijersbergen RL, Davidoff MJ, Liu Q, Bacchetti S, Haber DA, Weinberg RA (1997) hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90:785–795

    Article  PubMed  CAS  Google Scholar 

  • Mohle R, Bautz F, Rafii S, Moore MA, Brugger W, Kanz L (1998) The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood 91:4523–4530

    PubMed  CAS  Google Scholar 

  • Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J (1999) Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 99:1726–1732

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Murohara T, Ikeda H, Duan J, Shintani S, Sasaki KI, 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

    PubMed  CAS  Google Scholar 

  • Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, Lingner J, Harley CB, Cech TR (1997) Telomerase catalytic subunit homologs from fission yeast and human. Science 277:955–959

    Article  PubMed  CAS  Google Scholar 

  • Rafii S (2000) Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest 105:17–19

    Article  PubMed  CAS  Google Scholar 

  • Rajagopalan S, Mohler ER 3rd, Lederman RJ, Mendelsohn FO, Saucedo JF, Goldman CK, Blebea J, Macko J, Kessler PD, Rasmussen HS, Annex BH (2003) Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 108:1933–1938

    Article  PubMed  CAS  Google Scholar 

  • Risau W (1995) Differentiation of endothelium. FASEB J 9:926–933

    PubMed  CAS  Google Scholar 

  • Risau W, Flamme I (1995) Vasculogenesis. Annu Rev Cell Dev Biol 11:73–91

    Article  PubMed  CAS  Google Scholar 

  • Salcedo R, Wasserman K, Young HA, Grimm MC, Howard OM, Anver MR, Kleinman HK, Murphy WJ, Oppenheim JJ (1999) Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: in vivo neovascularization induced by stromal-derived factor-1alpha. Am J Pathol 154:1125–1135

    PubMed  CAS  Google Scholar 

  • Shake JG, Gruber PJ, Baumgartner WA, Senechal G, Meyers J, Redmond JM, Pittenger MF, Martin BJ (2002) Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects. Ann Thorac Surg 73:1919–1925; discussion 1926

    Article  PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Shintani S, Kusano K, Ii M, Iwakura A, Heyd L, Curry C, Wecker A, Gavin M, Ma H, Kearney M, Silver M, Thorne T, Murohara T, Losordo DW (2006) Synergistic effect of combined intramyocardial CD34+ cells and VEGF2 gene therapy after MI. Nat Clin Pract Cardiovasc Med 3[Suppl 1]:S123–S128

    Article  PubMed  CAS  Google Scholar 

  • Skinner JA, Cohen AT (1996) Amputation for premature peripheral atherosclerosis: do young patients do better? Lancet 348:1396

    Article  PubMed  CAS  Google Scholar 

  • Suzuki K, Murtuza B, Smolenski RT, Sammut IA, Suzuki N, Kaneda Y, Yacoub MH (2001) Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Circulation 104:I207–I212

    PubMed  CAS  Google Scholar 

  • 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 5:434–438

    Article  PubMed  CAS  Google Scholar 

  • Tepper OM, Galiano RD, Capla JM, Kalka C, Gagne PJ, Jacobowitz GR, Levine JP, Gurtner GC (2002) Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures. Circulation 106:2781–2786

    Article  PubMed  Google Scholar 

  • Thurston G, Suri C, Smith K, McClain J, Sato TN, Yancopoulos GD, McDonald DM (1999) Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science 286:2511–2514

    Article  PubMed  CAS  Google Scholar 

  • Vale PR, Rauh G, Wuensch DI, Pieczek A, Schainfeld RM (1998) Influence of vascular endothelial growth factor on diabetic retinopathy. Circulation 17:I–353

    Google Scholar 

  • Van Belle E, Tio F, Couffinhal T, Maillard L, Passeri J, Isner JM (1996) Stent endothelialization: time course, impact of local catheter delivery, feasibility of recombinant protein administration, and response to cytokine expedition. Circulation 94:I–259

    Google Scholar 

  • Van Belle E, Tio FO, Chen D, Maillard L, Kearney M, Isner JM (1997) Passivation of metallic stents following arterial gene transfer of phVEGF165 inhibits thrombus formation and intimal thickening. J Am Coll Cardiol 29:1371–1379

    Article  PubMed  Google Scholar 

  • Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89:E1–E7

    PubMed  CAS  Google Scholar 

  • 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 353:999–1007

    Article  PubMed  CAS  Google Scholar 

  • Wright WE, Shay JW (1992) The two-stage mechanism controlling cellular senescence and immortalization. Exp Gerontol 27:383–389

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi J, Kusano KF, Masuo O, Kawamoto A, Silver M, Murasawa S, Bosch-Marce M, Masuda H, Losordo DW, Isner JM, Asahara T (2003) Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 107:1322–1328

    Article  PubMed  CAS  Google Scholar 

  • Yoon YS, Park JS, Tkebuchava T, Luedeman C, Losordo DW (2004) Unexpected severe calcification after transplantation of bone marrow cells in acute myocardial infarction. Circulation 109:3154–3157

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, Caritas St. Elizabeth’s Medical Center, 736 Cambridge St., Boston, MA, 02135, USA

    A. Quraishi

  2. Northwestern University Feinberg School of Medicine, 303 East Chicago Ave., Tarry 12-703, Chicago, IL, 60611, USA

    D. W. Losordo

Authors
  1. A. Quraishi
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  2. D. W. Losordo
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Correspondence to D. W. Losordo .

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Editors and Affiliations

  1. Cardiovascular Disease Boehringer Ingelheim, Pharmaceuticals, Inc., 175 Briar Ridge Road, Ridgefield, CT, 06877, USA

    Katalin Kauser MD, PhD, DSc (Director) (Director)

  2. Department of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, D-60590, Frankfurt a. Main

    Andreas-Michael Zeiher MD (Professor Molecular Cardiology) (Professor Molecular Cardiology)

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© 2007 Springer-Verlag Berlin Heidelberg

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Quraishi, A., Losordo, D.W. (2007). Ischemic Tissue Repair by Autologous Bone Marrow-Derived Stem Cells: Scientific Basis and Preclinical Data. 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_7

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