International Journal of Gerontology
Volume 1, Issue 1 , Pages 10-21, March 2007

Therapeutic Application of Bone Marrow-derived Progenitor Cells for Vascular Diseases: Magicbullets Having the Good Without the Bad?

  • Kimie Tanaka

      Affiliations

    • Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    • ,
  • Masataka Sata

      Affiliations

    • Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    • Department of Advanced Clinical Science and Therapeutics, University of Tokyo Graduate School of Medicine, Tokyo, Japan
    • Corresponding Author InformationCorrespondence to: Dr Masataka Sata, Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-8655, Japan

Accepted 28 November 2006.

Article Outline

SUMMARY 

Accumulating evidence suggests that bone marrow-derived progenitor cells contribute to vascular healing and remodeling under physiologic and pathologic conditions. Although there is growing enthusiasm for therapeutic and diagnostic application of bone marrow-derived progenitors, there is a possibility that transplanted precursors or bone marrow cells may participate in the pathogenesis of unexpected diseases such as cancer, retinopathy, and atherosclerosis. The aim of this article is to review recent findings on bone marrow-derived progenitor cells obtained from animal models and clinical trials.

Key Words:  atherosclerosis , endothelial cells , progenitors , smooth muscle cells , stem cell

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References 

  1. Asahara T , Murohara T , Sullivan A , Silver M , van der Zee R , Li T , et al.   Isolation of putative progenitor endothelial cells for angiogenesis . Science . 1997;275:964–967
  2. Khakoo AY , Finkel T . Endothelial progenitor cells . Annu Rev Med . 2005;56:79–101
  3. Sata M , Saiura A , Kunisato A , Tojo A , Okada S , Tokuhisa T , et al.   Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis . Nat Med . 2002;8:403–409
  4. Sata M . Circulating vascular progenitor cells contribute to vascular repair, remodeling, and lesion formation . Trends Cardiovasc Med . 2003;13:249–253
  5. Saiura A , Sata M , Hirata Y , Nagai R , Makuuchi M . Circulating smooth muscle progenitor cells contribute to atherosclerosis . Nat Med . 2001;7:382–383
  6. Sarjeant JM , Rabinovitch M . Understanding and treating vein graft atherosclerosis . Cardiovasc Pathol . 2002;11:263–271
  7. Billingham ME . Cardiac transplant atherosclerosis . Transplant Proc . 1987;19:19–25
  8. Ross R . Atherosclerosis: a defense mechanism gone awry . Am J Pathol . 1993;143:985–1002
  9. Sata M , Maejima Y , Adachi F , Fukino K , Saiura A , Sugiura S , et al.   A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia . J Mol Cell Cardiol . 2000;32:2097–2104
  10. Furukawa Y , Matsumori A , Ohashi N , Shioi T , Ono K , Harada A , 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
  11. Hayashi S , Watanabe N , Nakazawa K , Suzuki J , Tsushima K , Tamatani T , et al.   Roles of P-selectin in inflammation, neointimal formation, and vascular remodeling in balloon-injured rat carotid arteries . Circulation . 2000;102:1710–1717
  12. Zohlnhofer D , Klein CA , Richter T , Brandl R , Murr A , Nuhrenberg 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
  13. 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
  14. 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
  15. Shimizu K , Sugiyama S , Aikawa M , Fukumoto Y , Rabkin E , Libby P , 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
  16. Hu Y , Davison F , Ludewig B , Erdel M , Mayr M , Url M , et al.   Smooth muscle cells in transplant atherosclerotic lesions are originated from recipients, but not bone marrow progenitor cells . Circulation . 2002;106:1834–1839
  17. Grimm PC , Nickerson P , Jeffery J , Savani RC , Gough J , McKenna RM , et al.   Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection . N Engl J Med . 2001;345:93–97
  18. 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
  19. Caplice NM , Bunch TJ , Stalboerger PG , Wang S , Simper D , Miller DV , 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
  20. Plump AS , Smith JD , Hayek T , Aalto-Setela K , Walsh A , Verstuyft JG , et al.   Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells . Cell . 1992;71:343–353
  21. Folkman J . Clinical applications of research on angiogenesis . N Engl J Med . 1995;333:1757–1763
  22. Ferrara N . Vascular endothelial growth factor and the regulation of angiogenesis . Recent Prog Horm Res . 2000;55:15–35
  23. Moulton KS , Vakili K , Zurakowski D , Soliman M , Butterfield C , Sylvin E , et al.   Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis . Proc Natl Acad Sci USA . 2003;100:4736–4741
  24. Moulton KS , Heller E , Konerding MA , Flynn E , Palinski W , Folkman J . Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice . Circulation . 1999;99:1726–1732
  25. Schatteman GC , Awad O . In vivo and in vitro properties of CD34+ and CD14+ endothelial cell precursors . Adv Exp Med Biol . 2003;522:9–16
  26. Asahara T , Masuda H , Takahashi T , Kalka C , Pastore C , Silver M , et al.   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization . Circ Res . 1999;85:221–228
  27. Kaplan RN , Riba RD , Zacharoulis S , Bramley AH , Vincent L , Costa C , et al.   VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche . Nature . 2005;438:820–827
  28. Otani A , Kinder K , Ewalt K , Otero FJ , Schimmel P , Friedlander M . Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis . Nat Med . 2002;8:1004–1010
  29. Hu Y , Davison F , Zhang Z , Xu Q . Endothelial replacement and angiogenesis in arteriosclerotic lesions of allografts are contributed by circulating progenitor cells . Circulation . 2003;108:3122–3127
  30. Jansen J , Hanks S , Thompson JM , Dugan MJ , Akard LP . Transplantation of hematopoietic stem cells from the peripheral blood . J Cell Mol Med . 2005;9:37–50
  31. Krause DS , Theise ND , Collector MI , Henegariu O , Hwang S , Gardner R , et al.   Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell . Cell . 2001;105:369–377
  32. Orlic D , Kajstura J , Chimenti S , Jakoniuk I , Anderson SM , Li B , et al.   Bone marrow cells regenerate infarcted myocardium . Nature . 2001;410:701–705
  33. Lagasse E , Connors H , Al-Dhalimy M , Reitsma M , Dohse M , Osborne L , et al.   Purified hematopoietic stem cells can differentiate into hepatocytes in vivo . Nat Med . 2000;6:1229–1234
  34. Sata M , Maejima Y , Adachi F , Fukino K , Saiura A , Sugiura S , et al.   A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia . J Mol Cell Cardiol . 2000;32:2097–2104
  35. Wagers AJ , Sherwood RI , Christensen JL , Weissman IL . Little evidence for developmental plasticity of adult hematopoietic stem cells . Science . 2002;297:2256–2259
  36. Balsam LB , Wagers AJ , Christensen JL , Kofidis T , Weissman IL , Robbins RC . Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium . Nature . 2004;428:668–673
  37. Sahara M , Sata M , Matsuzaki Y , Tanaka K , Morita T , Hirata 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
  38. Jiang Y , Jahagirdar BN , Reinhardt RL , Schwartz RE , Keene CD , Ortiz-Gonzalez XR , et al.   Pluripotency of mesenchymal stem cells derived from adult marrow . Nature . 2002;418:41–49
  39. Sata M , Nagai R . Inflammation, angiogenesis, and endothelial progenitor cells: how do endothelial progenitor cells find their place? . J Mol Cell Cardiol . 2004;36:459–463
  40. Hill JM , Zalos G , Halcox JP , Schenke WH , Waclawiw MA , Quyyumi AA , et al.   Circulating endothelial progenitor cells, vascular function, and cardiovascular risk . N Engl J Med . 2003;348:593–600
  41. Urbich C , Heeschen C , Aicher A , Dernbach E , Zeiher AM , Dimmeler S . Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells . Circulation . 2003;108:2511–2516
  42. Shintani S , Murohara T , Ikeda H , Ueno T , Honma T , Katoh A , et al.   Mobilization of endothelial progenitor cells in patients with acute myocardial infarction . Circulation . 2001;103:2776–2779
  43. Rauscher FM , Goldschmidt-Clermont PJ , Davis BH , Wang T , Gregg D , Ramaswami P , et al.   Aging, progenitor cell exhaustion, and atherosclerosis . Circulation . 2003;108:457–463
  44. Gill M , Dias S , Hattori K , Rivera ML , Hicklin D , Witte L , et al.   Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells . Circ Res . 2001;88:167–174
  45. Reyes M , Dudek A , Jahagirdar B , Koodie L , Marker PH , Verfaillie CM . Origin of endothelial progenitors in human postnatal bone marrow . J Clin Invest . 2002;109:337–346
  46. Amano K , Okigaki M , Adachi Y , Fujiyama S , Mori Y , Kosaki A , et al.   Mechanism for IL-1 beta-mediated neovascularization unmasked by IL-1 beta knock-out mice . J Mol Cell Cardiol . 2004;36:469–480
  47. Friedrich EB , Walenta K , Scharlau J , Nickenig G , Werner N . CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities . Circ Res . 2006;98:e20–e25
  48. Luttun A , Tjwa M , Moons L , Wu Y , Angelillo-Scherrer A , Liao F , et al.   Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1 . Nat Med . 2002;8:831–840
  49. Rafii S , Lyden D . Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration . Nat Med . 2003;9:702–712
  50. Paunescu V , Suciu E , Tatu C , Plesa A , Herman D , Siska IR , et al.   Endothelial cells from hematopoietic stem cells are functionally different from those of human umbilical vein . J Cell Mol Med . 2003;7:455–460
  51. Liu C , Nath KA , Katusic ZS , Caplice NM . Smooth muscle progenitor cells in vascular disease . Trends Cardiovasc Med . 2004;14:288–293
  52. Deb A , Skelding KA , Wang S , Reeder M , Simper D , Caplice NM . Integrin profile and in vivo homing of human smooth muscle progenitor cells . Circulation . 2004;110:2673–2677
  53. Zalewski A , Shi Y , Johnson AG . Diverse origin of intimal cells: smooth muscle cells, myofibroblasts, fibroblasts, and beyond? . Circ Res . 2002;91:652–655
  54. 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
  55. Hu Y , Zhang Z , Torsney E , Afzal AR , Davison F , Metzler B , et al.   Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoEdeficient mice . J Clin Invest . 2004;113:1258–1265
  56. Korbling M , Katz RL , Khanna A , Ruifrok AC , Rondon G , Albitar M , et al.   Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells . N Engl J Med . 2002;346:738–746
  57. Korbling M , Estrov Z . Adult stem cells for tissue repair— a new therapeutic concept? . N Engl J Med . 2003;349:570–582
  58. 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
  59. Terada N , Hamazaki T , Oka M , Hoki M , Mastalerz DM , Nakano Y , et al.   Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion . Nature . 2002;416:542–545
  60. Ying QL , Nichols J , Evans EP , Smith AG . Changing potency by spontaneous fusion . Nature . 2002;416:545–548
  61. Wang X , Willenbring H , Akkari Y , Torimaru Y , Foster M , Al-Dhalimy M , et al.   Cell fusion is the principal source of bone-marrow-derived hepatocytes . Nature . 2003;422:897–901
  62. Vassilopoulos G , Wang PR , Russell DW . Transplanted bone marrow regenerates liver by cell fusion . Nature . 2003;422:901–904
  63. Campbell JH , Tachas G , Black MJ , Cockerill G , Campbell GR . Molecular biology of vascular hypertrophy . Basic Res Cardiol . 1991;86:3–11
  64. Saiura A , Sata M , Washida M , Sugawara Y , Hirata Y , Nagai R , et al.   Little evidence for cell fusion between recipient and donor-derived cells . J Surg Res . 2003;113:222–227
  65. Oh H , Bradfute SB , Gallardo TD , Nakamura T , Gaussin V , Mishina Y , et al.   Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction . Proc Natl Acad Sci USA . 2003;100:12313–12318
  66. 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
  67. Jacobs AK . Coronary stents—have they fulfilled their promise? . N Engl J Med . 1999;341:2005–2006
  68. Moses JW , Leon MB , Popma JJ , Fitzgerald PJ , Holmes DR , O'Shaughnessy C , et al.   Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery . N Engl J Med . 2003;349:1315–1323
  69. Daemen J , Ong AT , Stefanini GG , Tsuchida K , Spindler H , Sianos G , et al.   Three-year clinical follow-up of the unrestricted use of sirolimus-eluting stents as part of the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) Registry . Am J Cardiol . 2006;98:895–901
  70. Marks AR . Sirolimus for the prevention of in-stent restenosis in a coronary artery . N Engl J Med . 2003;349:1307–1309
  71. Fukuda D , Sata M , Tanaka K , Nagai R . Potent inhibitory effect of sirolimus on circulating vascular progenitor cells . Circulation . 2005;111:926–931
  72. McFadden EP , Stabile E , Regar E , Cheneau E , Ong AT , Kinnaird T , et al.   Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy . Lancet . 2004;364:1519–1521
  73. Walsh K , Sata M . Is extravasation a Fas-regulated process? . Mol Med Today . 1999;7:61–67
  74. Walsh K , Sata M . Negative regulation of inflammation by Fas ligand expression on the vascular endothelium . Trends Cardiovasc Med . 1999;9:34–41
  75. Nagata S , Golstein P . The Fas death factor . Science . 1995;267:1449–1456
  76. Nagata S . Apoptosis by death factor . Cell . 1997;88:355–365
  77. Sata M , Perlman H , Muruve DA , Silver M , Ikebe M , Libermann TA , 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
  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
  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
  80. Sata M , Walsh K . TNFα regulation of Fas ligand expression on the vascular endothelium modulates leukocyte extravasation . Nat Med . 1998;4:415–420
  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
  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
  83. Anglani F , Forino M , Del Prete D , Tosetto E , Torregrossa R , D'Angelo A . In search of adult renal stem cells . J Cell Mol Med . 2004;8:474–487
  84. Smits AM , van Vliet P , Hassink RJ , Goumans MJ , Doevendans PA . The role of stem cells in cardiac regeneration . J Cell Mol Med . 2005;9:25–36
  85. Reya T , Morrison SJ , Clarke MF , Weissman IL . Stem cells, cancer, and cancer stem cells . Nature . 2001;414:105–111
  86. Sata M , Saiura A , Kunisato A , Tojo A , Okada S , Tokuhisa T , et al.   Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis . Nat Med . 2002;8:403–409
  87. Saiura A , Sata M , Hirata Y , Nagai R , Makuuchi M . Circulating smooth muscle progenitor cells contribute to atherosclerosis . Nat Med . 2001;7:382–383
  88. Tateishi-Yuyama E , Matsubara H , Murohara T , Ikeda U , Shintani S , Masaki H , et al.   Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomized controlled trial . Lancet . 2002;360:427–435
  89. Assmus B , Schachinger V , Teupe C , Britten M , Lehmann R , Dobert N , et al.   Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) . Circulation . 2002;106:3009–3017
  90. Strauer BE , Brehm M , Zeus T , Kostering M , Hernandez A , Sorg RV , et al.   Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans . Circulation . 2002;106:1913–1918
  91. Meyer GP , Wollert KC , Lotz J , Steffens J , Lippolt P , Fichtner S , et al.   Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' followup data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial . Circulation . 2006;113:1287–1294
  92. Ziegelhoeffer T , Fernandez B , Kostin S , Heil M , Voswinckel R , Helisch A , et al.   Bone marrow-derived cells do not incorporate into the adult growing vasculature . Circ Res . 2004;94:230–238
  93. Urbich C , Dimmeler S . Endothelial progenitor cells: characterization and role in vascular biology . Circ Res . 2004;95:343–353
  94. O'Neill TJT , Wamhoff BR , Owens GK , Skalak TC . Mobilization of bone marrow-derived cells enhances the angiogenic response to hypoxia without transdifferentiation into endothelial cells . Circ Res . 2005;97:1027–1035
  95. Kinnaird T , Stabile E , Burnett MS , Epstein SE . Bonemarrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences . Circ Res . 2004;95:354–363
  96. Kang HJ , Kim HS , Zhang SY , Park KW , Cho HJ , Koo BK , et al.   Effects of intracoronary infusion of peripheral blood stem-cells mobilised 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
  97. Silvestre JS , Gojova A , Brun V , Potteaux S , Esposito B , Duriez M , et al.   Transplantation of bone marrowderived mononuclear cells in ischemic apolipoprotein E-knockout mice accelerates atherosclerosis without altering plaque composition . Circulation . 2003;108:2839–2842
  98. Assmus B , Honold J , Schachinger V , Britten MB , Fischer-Rasokat U , Lehmann R , et al.   Transcoronary transplantation of progenitor cells after myocardial infarction . N Engl J Med . 2006;355:1222–1232
  99. Schachinger V , Erbs S , Elsasser A , Haberbosch W , Hambrecht R , Holschermann H , et al.   Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction . N Engl J Med . 2006;355:1210–1221
  100. Lunde K , Solheim S , Aakhus S , Arnesen H , Abdelnoor M , Egeland T , et al.   Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction . N Engl J Med . 2006;355:1199–1209

PII: S1873-9598(08)70019-X

doi:10.1016/S1873-9598(08)70019-X

International Journal of Gerontology
Volume 1, Issue 1 , Pages 10-21, March 2007

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