Skip to main content
SpringerLink
Log in

Contribution of Circulating Progenitor Cells to Vascular Repair and Lesion Formation

  • Chapter
Book cover Essentials of Restenosis

Part of the book series: Contemporary Cardiology ((CONCARD))

  • 715 Accesses

Abstract

The accumulation of smooth muscle cells (SMCs) plays a principal role in atherogenesis, postangioplasty restenosis, and transplantation-associated vasculopathy. Therefore, much effort has been expended in targeting the migration and proliferation of medial SMCs to prevent occlusive vascular remodeling. Recent findings have suggested that bone marrow-derived precursors can also give rise to vascular cells that contribute to repair, remodeling, and lesion formation. This article overviews recent findings on circulating vascular progenitor cells and describes potential therapeutic strategies that target these cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ross R. Atherosclerosis-An inflammatory disease. N Eng J Med 1999;340:115–126.

    Article  CAS  Google Scholar 

  2. Ross R. Rous-Whipple Award Lecture. Atherosclerosis: a defense mechanism gone awry. Am J Pathol 1993;143:987–1002.

    PubMed  CAS  Google Scholar 

  3. Ross R. Genetically modified mice as models of transplant atherosclerosis. Nat Med 1996;2:527–528.

    Article  PubMed  CAS  Google Scholar 

  4. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801–809.

    Article  PubMed  CAS  Google Scholar 

  5. Nobuyoshi M, Kimura T, Nosaka H, et al. Restenosis after successful percutaneous transluminal coronary angioplasty: serial angiographic follow-up of 229 patients. J Am Coll Cardiol 1988;12:616–623.

    PubMed  CAS  Google Scholar 

  6. Kearney M, Pieczek A, Haley L, et al. Histopathology of in-stent restenosis in patients with peripheral artery disease. Circulation 1997;95:1998–2002.

    PubMed  CAS  Google Scholar 

  7. Callow AD. Molecular biology of graft occlusion. Curr Opin Cardiol 1995;10:569–576.

    Article  PubMed  CAS  Google Scholar 

  8. Sarjeant JM, Rabinovitch M. Understanding and treating vein graft atherosclerosis. Cardiovasc Pathol 2002;11:263–271.

    Article  PubMed  Google Scholar 

  9. Billingham ME. Cardiac transplant atherosclerosis. Transplant Proc 1987;19:19–25.

    PubMed  CAS  Google Scholar 

  10. Clausell N, Milossi S, Sett S, Rabinovitch M. In vivo blockade of tumor necrosis factor-α in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation. Circulation 1 1994;89:2768–2779.

    CAS  Google Scholar 

  11. Chang MW, Barr E, Lu MM, Barton K, Leiden JM. Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. J Clin Invest 1995;96:2260–2268.

    PubMed  CAS  Google Scholar 

  12. Smith RC, Wills KN, Antelman D, et al. Adenoviral constructs encoding phosphorylation-competent full-length and truncated forms of the human retinoblastoma protein inhibit myocyte proliferation and neointima formation. Circulation 1997;96:1899–1905.

    PubMed  CAS  Google Scholar 

  13. Pollman MJ, Hall JL, Mann MJ, Zhang L, Gibbons GH. Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nature Med 1998;4:222–227.

    Article  PubMed  CAS  Google Scholar 

  14. Chen D, Krasinski K, Chen D, et al. Down-regulation of cyclin-dependent kinase activity and cyclin A promoter activity in vascular smooth muscle cells by p27 (KIP-1), an inhibitor of neointima formation in the rat carotid artery. J Clin Invest 1997;99:2334–2341.

    PubMed  CAS  Google Scholar 

  15. George SJ, Johnson JL, Angelini GD, Newby AC, Baker AH. Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle cell migration and neointimal formation in human saphenous veins. Hum Gene Ther 1998;9:867–877.

    PubMed  CAS  Google Scholar 

  16. George SJ, Angelini GD, Capogrossi MC, Baker AH. Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis. Gene Ther 2001;8:668–676.

    Article  PubMed  CAS  Google Scholar 

  17. Izawa A, Suzuki J, Takahashi W, Amano J, Isobe M. Tranilast inhibits cardiac allograft vasculopathy in association with p21(Waf1/Cip1) expression on neointimal cells in murine cardiac transplantation model. Arterioscler Thromb Vasc Biol 2001;21:1172–1178.

    Article  PubMed  CAS  Google Scholar 

  18. Rebsamen MC, Sun J, Norman AW, Liao JK. 1alpha,25-dihydroxyvitamin D3 induces vascular smooth muscle cell migration via activation of phosphatidylinositol 3-kinase. Circ Res 2002;91:17–24.

    Article  PubMed  CAS  Google Scholar 

  19. Ohno T, Gordon D, San H, et al. Gene therapy for vascular smooth muscle cell proliferation after arterial injury. Science 1994;265:781–784.

    Article  PubMed  CAS  Google Scholar 

  20. Yang Z, Simari R, Perkins N, et al. Role of the p21cyclin-dependent kinase inhibitor in limiting intimal cell proliferation in response to arterial injury. Proc Natl Acad Sci USA 1996;93:7905–7910.

    Article  PubMed  CAS  Google Scholar 

  21. Chang MW, Barr E, Seltzer J, et al. Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of the retinoblastoma gene product. Science 1995;267:518–522.

    Article  PubMed  CAS  Google Scholar 

  22. Sata M, Maejima Y, Adachi F, et al. A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neoin-timal hyperplasia. J Mol Cell Cardiol 2000;32:2097–2104.

    Article  PubMed  CAS  Google Scholar 

  23. Feldman LJ, Mazighi M, Scheuble A, et al. Differential expression of matrix metalloproteinases after stent implantation and balloon angioplasty in the hypercholesterolemic rabbit. Circulation 2001;103:3117–3122.

    PubMed  CAS  Google Scholar 

  24. Furukawa Y, Matsumori A, Ohashi N, et al. Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries. Circ Res 1999;84:306–314.

    PubMed  CAS  Google Scholar 

  25. Hayashi S, Watanabe N, Nakazawa K, et al. Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries. Circulation 2000;102:1710–1717.

    PubMed  CAS  Google Scholar 

  26. Zohlnhofer D, Klein CA, Richter T, et al. Gene expression profiling of human stent-induced neointima by cDNA array analysis of microscopic specimens retrieved by helix cutter atherectomy: detection of FK506-binding protein 12 upregulation. Circulation 2001;103:1396–1402.

    PubMed  CAS  Google Scholar 

  27. Zohlnhofer D, Richter T, Neumann FJ, et al. Transcriptome analysis reveals a role of interferon-gamma in human neointima formation. Mol Cell 2001;7:1059–1069.

    Article  PubMed  CAS  Google Scholar 

  28. Saiura A, Sata M, Hirata Y, Nagai R, Makuuchi M. Circulating smooth muscle progenitor cells contribute to atherosclerosis. Nat Med 2001;7:382–383.

    Article  PubMed  CAS  Google Scholar 

  29. Sata M, Saiura A, Kunisato A, et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 2002;8:403–409.

    Article  PubMed  CAS  Google Scholar 

  30. Sata M. Circulating vascular progenitor cells contribute to vascular repair, remodeling, and lesion formation. Trends Cardiovasc Med 2003;13:249–253.

    Article  PubMed  Google Scholar 

  31. Tanaka K, Sata M, Hirata Y, Nagai R. Diverse contribution of bone marrow cells to neointimal hyperplasia after mechanical vascular injuries. Circ Res 2003;93:783–790.

    Article  PubMed  CAS  Google Scholar 

  32. Friedrich G, Soriano P. Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev 1991;5:1513–1523.

    Article  PubMed  CAS  Google Scholar 

  33. Zambrowicz BP, Imamoto A, Fiering S, Herzenberg LA, Kerr WG, Soriano P. Disruption of overlapping transcripts in the ROSA βgeo 26 gene trap strain leads to widespread expression of β-galactosidase in mouse embryos and hematopoietic cells. Proc Natl Acad Sci USA 19 1997;94:3789–379

    Article  CAS  Google Scholar 

  34. Shimizu K, Sugiyama S, Aikawa M, et al. Host bone-marrow cells are a source of donor intimal smooth-muscle-like cells in murine aortic transplant arteriopathy. Nat Med 2001;7:738–741.

    Article  PubMed  CAS  Google Scholar 

  35. Hillebrands JL, Klatter FA, van Den Hurk BM, Popa ER, Nieuwenhuis P, Rozing J. Origin of neointimal endothelium and alpha-actin-positive smooth muscle cells in transplant arteriosclerosis. J Clin Invest 2001;107:1411–1422.

    Article  PubMed  CAS  Google Scholar 

  36. Hu Y, Davison F, Ludewig B, et al. Smooth muscle cells in transplant atherosclerotic lesions are originated from recipients, but not bone marrow progenitor cells. Circulation 2002;106:1834–1839.

    Article  PubMed  Google Scholar 

  37. Hillebrands JL, Klatter FA, Rozing J. Origin of vascular smooth muscle cells and the role of circulating stem cells in transplant arteriosclerosis. Arterioscler Thromb Vasc Biol 2003;23:380–387.

    Article  PubMed  CAS  Google Scholar 

  38. Hillebrands JL, Klatter FA, van Dijk WD, Rozing J. Bone marrow does not contribute substantially to endothelial-cell replacement in transplant arteriosclerosis. Nat Med 2002;8:194–195.

    Article  PubMed  Google Scholar 

  39. Hillebrands J, vdH BM, Klatter FA, Popa ER, Nieuwenhuis P, Rozing J. Recipient origin of neointimal vascular smooth muscle cells in cardiac allografts with transplant arteriosclerosis. J Heart Lung Transplant 2000;19:1183–1192.

    Article  PubMed  CAS  Google Scholar 

  40. Grimm PC, Nickerson P, Jeffery J, et al. Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection. N Engl J Med 2001;345:93–97.

    Article  PubMed  CAS  Google Scholar 

  41. Lagaaij EL, Cramer-Knijnenburg GF, van Kemenade FJ, van Es LA, Bruijn JA, van Krieken JH. Endothelial cell chimerism after renal transplantation and vascular rejection. Lancet 2001;357:33–37.

    Article  PubMed  CAS  Google Scholar 

  42. Sata M, Sugiura S, Yoshizumi M, Ouchi Y, Hirata Y, Nagai R. Acute and chronic smooth muscle cell apoptosis after mechanical vascular injury can occur independently of the Fas-death pathway. Arterioscler Thromb Vasc Biol 2001;21:1733–1737.

    Article  PubMed  CAS  Google Scholar 

  43. Sata M, Tanaka K, Ishizaka N, Hirata Y, Nagai R. Absence of p53 Leads to Accelerated Neointimal Hyperplasia After Vascular Injury. Arterioscler Thromb Vasc Biol 2003;23:1548–1552.

    Article  PubMed  CAS  Google Scholar 

  44. Perlman H, Maillard L, Krasinski K, Walsh K. Evidence for the rapid onset of apoptosis in medial smooth muscle cells following balloon injury. Circulation 1997;95:981–987.

    PubMed  CAS  Google Scholar 

  45. Plump AS, Smith JD, Hayek T, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992;71:343–353.

    Article  PubMed  CAS  Google Scholar 

  46. Li S, Fan YS, Chow LH, et al. Innate diversity of adult human arterial smooth muscle cells: cloning of distinct subtypes from the internal thoracic artery. Circ Res 2001;89:517–525.

    Article  PubMed  CAS  Google Scholar 

  47. Zalewski A, Shi Y, Johnson AG. Diverse origin of intimal cells: smooth muscle cells, myofibroblasts, fibroblasts, and beyond? Circ Res 2002;91:652–655.

    Article  PubMed  CAS  Google Scholar 

  48. Kaushal S, Amiel GE, Guleserian KJ, et al. Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 2001;7:1035–1040.

    Article  PubMed  CAS  Google Scholar 

  49. Caplice NM, Bunch TJ, Stalboerger PG, et al. Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Proc Natl Acad Sci USA 2003;100:4754–4759.

    Article  PubMed  CAS  Google Scholar 

  50. Osawa M, Hanada K, Hamada H, Nakauchi H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996;273:242–245.

    Article  PubMed  CAS  Google Scholar 

  51. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997;276:71–74.

    Article  PubMed  CAS  Google Scholar 

  52. Krause DS, Theise ND, Collector MI, et al. Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 2001;105:369–377.

    Article  PubMed  CAS  Google Scholar 

  53. Alison MR, Poulsom R, Jeffery R, et al. Hepatocytes from non-hepatic adult stem cells. Nature 2000;406:257.

    Article  PubMed  CAS  Google Scholar 

  54. Lagasse E, Connors H, Al-Dhalimy M, et al. Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 2000;6:1229–1234.

    Article  PubMed  CAS  Google Scholar 

  55. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infracted myocardium. Nature 2001;410:701–705.

    Article  PubMed  CAS  Google Scholar 

  56. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infracted heart, improving function and survival. Proc Natl Acad Sci USA 2001;98:10,344–10,349.

    Article  CAS  Google Scholar 

  57. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 2002;297:2256–2259.

    Article  PubMed  CAS  Google Scholar 

  58. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium. Nature 2004;428:607–608.

    Article  CAS  Google Scholar 

  59. Sahara M, Sata M, Matsuzaki Y, et al. Comparison of various bone marrow fractions in the ability to participate in vascular remodeling after mechanical injury. Stem Cells 2005;23:874–878.

    Article  PubMed  Google Scholar 

  60. Korbling M, Estrov Z. Adult stem cells for tissue repair — a new therapeutic concept? N Engl J Med 2003;349:570–582.

    Article  PubMed  Google Scholar 

  61. LaBarge MA, Blau HM. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 2002;111:589–601.

    Article  PubMed  CAS  Google Scholar 

  62. Terada N, Hamazaki T, Oka M, et al. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 2002;416:542–545.

    Article  PubMed  CAS  Google Scholar 

  63. Ying QL, Nichols J, Evans EP, Smith AG. Changing potency by spontaneous fusion. Nature 2002;416:545–548.

    Article  PubMed  CAS  Google Scholar 

  64. Wang X, Willenbring H, Akkari Y, et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 2003;422:897–901.

    Article  PubMed  CAS  Google Scholar 

  65. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 2003;422:901–904.

    Article  PubMed  CAS  Google Scholar 

  66. Campbell JH, Tachas G, Black MJ, Cockerill G, Campbell GR. Molecular biology of vascular hypertrophy. Basic Res Cardiol 1991;86(Suppl 1):3–11.

    PubMed  CAS  Google Scholar 

  67. Saiura A, Sata M, Washida M, et al. Little evidence for cell fusion between recipient and Donor-Derived cells. J Surg Res 2003;13:222–227.

    Article  Google Scholar 

  68. Walsh K, Perlman H. Molecular strategies to inhibit restenosis: modulation of the vascular myocyte phenotype. Semin Interv Cardiol 1996;1:173–179.

    PubMed  CAS  Google Scholar 

  69. Miller AM, McPhaden AR, Wadsworth RM, Wainwright CL. Inhibition by leukocyte depletion of neointima formation after balloon angioplasty in a rabbit model of restenosis. Cardiovasc Res 2001;49:838–850.

    Article  PubMed  CAS  Google Scholar 

  70. Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773–1780.

    Article  PubMed  CAS  Google Scholar 

  71. Fattori R, Piva T. Drug-eluting stents in vascular intervention. Lancet 2003;361:247–249.

    Article  PubMed  Google Scholar 

  72. Fukuda D, Sata M, Tanaka K, Nagai R. Potent inhibitory effect of sirolimus on circulating vascular progenitor cells. Circulation 2005;111:926–931.

    Article  PubMed  CAS  Google Scholar 

  73. Walsh K, Sata M. Is extravasation a Fas-regulated process? Mol Med Today 1999;7:61–67.

    Article  Google Scholar 

  74. Walsh K, Sata M. Negative regulation of inflammation by Fas ligand expression on the vascular endothelium. Trends Cardiovasc Med 1999;9:34–41.

    Article  PubMed  CAS  Google Scholar 

  75. Nagata S, Golstein P. The Fas death factor. Science 1995;267:1449–1456.

    Article  PubMed  CAS  Google Scholar 

  76. Nagata S. Apoptosis by death factor. Cell 1997;88:355–365.

    Article  PubMed  CAS  Google Scholar 

  77. Sata M, Perlman H, Muruve DA, et al. Fas ligand gene transfer to the vessel wall inhibits neointima formation and overrides the adenovirus-mediated T cell response. Proc Natl Acad Sci USA 1998;95:1213–1217.

    Article  PubMed  CAS  Google Scholar 

  78. Sata M, Luo Z, Walsh K. Fas ligand overexpression on allograft endothelium inhibits inflammatory cell infiltration and transplant-associated intimal hyperplasia. J Immunol 2001;66:6964–6971.

    Google Scholar 

  79. Luo Z, Sata M, Nguyen T, Kaplan JM, Akita GY, Walsh K. Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals. Circulation 1999;99:1776–1779.

    PubMed  CAS  Google Scholar 

  80. Sata M, Walsh K. TNFα Regulation of Fas ligand expression on the vascular endothelium modulates leukocyte extravasation. Nature Med 1 1998;4:415–420.

    Article  CAS  Google Scholar 

  81. Richardson BC, Lalwani ND, Johnson KJ, Marks RM. Fas ligation triggers apoptosis in macrophages but not endothelial cells. Eur J Immunol 1994;24:2640–2645.

    Article  PubMed  CAS  Google Scholar 

  82. Sata M, Suhara T, Walsh K. Vascular endothelial cells and smooth muscle cells differ in expression of Fas and Fas ligand and in sensitivity to Fas Ligand induced cell death: Implications for vascular disease and therapy. Arterioscler Thromb Vasc Biol 2000;20:309–316.

    PubMed  CAS  Google Scholar 

  83. Yang J, Jones SP, Suhara T, et al. Endothelial cell overexpression of fas ligand attenuates ischemia-reperfusion injury in the heart. J Biol Chem 2003;278:15,185–15,191.

    CAS  Google Scholar 

  84. McKay R. Stem cells-hype and hope. Nature 2000;406:361–364.

    Article  PubMed  CAS  Google Scholar 

  85. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001;414:105–111.

    Article  PubMed  CAS  Google Scholar 

  86. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumor growth in immunodeficient mice. Nature 2 2007;445:106–110.

    Article  CAS  Google Scholar 

  87. Silvestre JS, Gojova A, Brun V, et al. Transplantation of bone marrow-derived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition. Circulation 2003;108:2839–2842.

    Article  PubMed  Google Scholar 

  88. Kang HJ, Kim HS, Zhang SY, et al. Effects of intracoronary infusion of peripheral blood stem-cells mobilized with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomized clinical trial. Lancet 2004;363:751–756.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan

    Masataka Sata MD, PhD

  2. Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA

    Kenneth Walsh PhD

Authors
  1. Masataka Sata MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenneth Walsh PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Thoraxcenter, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    Henricus J. Duckers MD, PhD  & Patrick W. Serruys MD, PhD  & 

  2. The Nabel Lab, Genome Technology Branch, NHGRI Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD

    Elizabeth G. Nabel MD

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc.

About this chapter

Cite this chapter

Sata, M., Walsh, K. (2007). Contribution of Circulating Progenitor Cells to Vascular Repair and Lesion Formation. In: Duckers, H.J., Nabel, E.G., Serruys, P.W. (eds) Essentials of Restenosis. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59745-001-0_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-001-0_11

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-491-3

  • Online ISBN: 978-1-59745-001-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation