Annals of Hematology

, Volume 92, Issue 11, pp 1461–1472 | Cite as

Isolation and characterization of mouse bone marrow-derived Lin/VEGF-R2+ progenitor cells

  • Daniel Barthelmes
  • Mohammad R. Irhimeh
  • Mark C. Gillies
  • Ling Zhu
  • Weiyong Shen
Original Article

Abstract

Circulating endothelial progenitor cells (EPCs) in the peripheral blood (PB) have physiological roles in the maintenance of the existing vascular beds and rescue of vascular injury. In this study, we have evaluated the properties of Lin/VEGF-R2+ progenitor cells isolated from the mouse bone marrow (BM) and further studied their distribution and integration in an animal model of laser-induced retinal vascular injury. Lin/VEGF-R2+ cells were enriched from C57BL/6 mice BM using magnetic cell sorting with hematopoietic lineage (Lin) depletion followed by VEGF-R2 positive selection. Lin/VEGF-R2+ BM cells were characterized using flow cytometry and immunocytochemistry and further tested for colony formation during culture and tube formation on Matrigel®. Lin/VEGF-R2+ BM cells possessed typical EPC properties such as forming cobble-stone shaped colonies after 3 to 4 weeks of culture, CD34+ expression, take up of Dil-acLDL and binding to Ulex europaeus agglutinin. However, they did not form tube-like structures on Matrigel®. The progenitor cells retained their phenotype over extended period of culture. After intravitreal transplantation in eyes subjected to the laser-induced retinal vascular injury, some Lin/VEGF-R2+ cells were able to integrate into the damaged retinal vasculature but the level of cell integration seemed less efficient when compared with previous reports in which EPCs from the human PB were employed. Our results indicate that Lin/VEGF-R2+ cells isolated from the mouse BM share some similarities to EPCs from the human PB but most of them are at a very early stage of maturation and remain quiescent during culture and after intravitreal transplantation.

Key words

Regenerative medicine Endothelial progenitor cells Intravitreal transplantation Bone marrow Stem cells Vasculogenesis 

References

  1. 1.
    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):964–967PubMedCrossRefGoogle Scholar
  2. 2.
    Liew A, McDermott JH, Barry F, O'Brien T (2008) Endothelial progenitor cells for the treatment of diabetic vasculopathy: panacea or Pandora's box? Diabetes Obes Metab 10(5):353–366. doi:10.1111/j.1463-1326.2007.00754.x PubMedCrossRefGoogle Scholar
  3. 3.
    Grant MB, May WS, Caballero S, Brown GA, Guthrie SM, Mames RN, Byrne BJ, Vaught T, Spoerri PE, Peck AB, Scott EW (2002) Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nat Med 8(6):607–612PubMedCrossRefGoogle Scholar
  4. 4.
    Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, Compernolle V, Daci E, Bohlen P, Dewerchin M, Herbert JM, Fava R, Matthys P, Carmeliet G, Collen D, Dvorak HF, Hicklin DJ, Carmeliet P (2002) Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 8(8):831–840PubMedGoogle Scholar
  5. 5.
    Isner JM, Kalka C, Kawamoto A, Asahara T (2001) Bone marrow as a source of endothelial cells for natural and iatrogenic vascular repair. Ann N Y Acad Sci 953:75–84PubMedCrossRefGoogle Scholar
  6. 6.
    Rafii S, Lyden D, Benezra R, Hattori K, Heissig B (2002) Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2(11):826–835PubMedCrossRefGoogle Scholar
  7. 7.
    Ruzinova MB, Schoer RA, Gerald W, Egan JE, Pandolfi PP, Rafii S, Manova K, Mittal V, Benezra R (2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer Cell 4(4):277–289PubMedCrossRefGoogle Scholar
  8. 8.
    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):593–600PubMedCrossRefGoogle Scholar
  9. 9.
    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:10.1161/CIRCULATIONAHA.104.504340 PubMedCrossRefGoogle Scholar
  10. 10.
    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):999–1007PubMedCrossRefGoogle Scholar
  11. 11.
    Sekiguchi H, Ii M, Losordo DW (2009) The relative potency and safety of endothelial progenitor cells and unselected mononuclear cells for recovery from myocardial infarction and ischemia. J Cell Physiol 219(2):235–242. doi:10.1002/jcp.21672 PubMedCrossRefGoogle Scholar
  12. 12.
    Rafii S, Lyden D (2003) Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat Med 9(6):702–712PubMedCrossRefGoogle Scholar
  13. 13.
    Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T (2002) Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet 360(9331):427–435PubMedCrossRefGoogle Scholar
  14. 14.
    Jung KH, Roh JK (2008) Circulating endothelial progenitor cells in cerebrovascular disease. J Clin Neurol 4(4):139–147. doi:10.3988/jcn.2008.4.4.139 PubMedCrossRefGoogle Scholar
  15. 15.
    Couffinhal T, Silver M, Kearney M, Sullivan A, Witzenbichler B, Magner M, Annex B, Peters K, Isner JM (1999) Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE−/− mice. Circulation 99(24):3188–3198PubMedCrossRefGoogle Scholar
  16. 16.
    Caballero S, Sengupta N, Afzal A, Chang KH, Li Calzi S, Guberski DL, Kern TS, Grant MB (2007) Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells. Diabetes 56(4):960–967. doi:10.2337/db06-1254 PubMedCrossRefGoogle Scholar
  17. 17.
    Ingram DA, Mead LE, Tanaka H, Meade V, Fenoglio A, Mortell K, Pollok K, Ferkowicz MJ, Gilley D, Yoder MC (2004) Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood 104(9):2752–2760. doi:10.1182/blood-2004-04-13962004-04-1396 PubMedCrossRefGoogle Scholar
  18. 18.
    Walenta K, Friedrich EB, Sehnert F, Werner N, Nickenig G (2005) In vitro differentiation characteristics of cultured human mononuclear cells-implications for endothelial progenitor cell biology. Biochem Biophys Res Commun 333(2):476–482. doi:10.1016/j.bbrc.2005.05.153 PubMedCrossRefGoogle Scholar
  19. 19.
    Bellik L, Ledda F, Parenti A (2005) Morphological and phenotypical characterization of human endothelial progenitor cells in an early stage of differentiation. FEBS Lett 579(12):2731–2736. doi:10.1016/j.febslet.2005.04.003 PubMedCrossRefGoogle Scholar
  20. 20.
    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):1527–1536PubMedCrossRefGoogle Scholar
  21. 21.
    Ishikawa M, Asahara T (2004) Endothelial progenitor cell culture for vascular regeneration. Stem Cells Dev 13(4):344–349. doi:10.1089/1547328041797435 PubMedCrossRefGoogle Scholar
  22. 22.
    Friedrich EB, Walenta K, Scharlau J, Nickenig G, Werner N (2006) CD34−/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities. Circ Res 98(3):e20–e25. doi:10.1161/01.RES.0000205765.28940.93 PubMedCrossRefGoogle Scholar
  23. 23.
    Medina R, O'Neill CL, Humphreys MW, Gardiner TA, Stitt AW (2010) Outgrowth endothelial cells: characterisation and their potential for reversing ischaemic retinopathy. Invest Ophthalmol Vis Sci 51(11):5906–5913. doi:10.1167/iovs.09-4951 PubMedCrossRefGoogle Scholar
  24. 24.
    Critser PJ, Voytik-Harbin SL, Yoder MC (2011) Isolating and defining cells to engineer human blood vessels. Cell Prolif 44(Suppl 1):15–21. doi:10.1111/j.1365-2184.2010.00719.x PubMedCrossRefGoogle Scholar
  25. 25.
    Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, Friedlander M (2002) Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 8(9):1004–1010PubMedCrossRefGoogle Scholar
  26. 26.
    Barber CL, Iruela-Arispe ML (2006) The ever-elusive endothelial progenitor cell: identities, functions and clinical implications. Pediatr Res 59(4 Pt 2):26R–32R. doi:10.1203/01.pdr.0000203553.46471.18 PubMedCrossRefGoogle Scholar
  27. 27.
    Hirschi KK, Ingram DA, Yoder MC (2008) Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 28(9):1584–1595. doi:10.1161/ATVBAHA.107.155960 PubMedCrossRefGoogle Scholar
  28. 28.
    Aicher A, Heeschen C, Mildner-Rihm C, Urbich C, Ihling C, Technau-Ihling K, Zeiher AM, Dimmeler S (2003) Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 9(11):1370–1376PubMedCrossRefGoogle Scholar
  29. 29.
    Butler JM, Guthrie SM, Koc M, Afzal A, Caballero S, Brooks HL, Mames RN, Segal MS, Grant MB, Scott EW (2005) SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest 115(1):86–93PubMedGoogle Scholar
  30. 30.
    Otani A, Dorrell MI, Kinder K, Moreno SK, Nusinowitz S, Banin E, Heckenlively J, Friedlander M (2004) Rescue of retinal degeneration by intravitreally injected adult bone marrow-derived lineage-negative hematopoietic stem cells. J Clin Invest 114(6):765–774PubMedGoogle Scholar
  31. 31.
    Wang QR, Wang BH, Huang YH, Dai G, Li WM, Yan Q (2008) Purification and growth of endothelial progenitor cells from murine bone marrow mononuclear cells. J Cell Biochem 103(1):21–29. doi:10.1002/jcb.21377 PubMedCrossRefGoogle Scholar
  32. 32.
    Shapiro HM (1988) Practical flow cytometry, 2nd edn. John Wiley & Sons, New YorkGoogle Scholar
  33. 33.
    Thum T, Fraccarollo D, Schultheiss M, Froese S, Galuppo P, Widder JD, Tsikas D, Ertl G, Bauersachs J (2007) Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes. Diabetes 56(3):666–674. doi:10.2337/db06-0699 PubMedCrossRefGoogle Scholar
  34. 34.
    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 U S A 97(7):3422–3427PubMedCrossRefGoogle Scholar
  35. 35.
    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):399–405PubMedGoogle Scholar
  36. 36.
    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):952–958PubMedGoogle Scholar
  37. 37.
    Ingram DA, Lien IZ, Mead LE, Estes M, Prater DN, Derr-Yellin E, DiMeglio LA, Haneline LS (2008) In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell numbers and function. Diabetes 57(3):724–731. doi:10.2337/db07-1507 PubMedCrossRefGoogle Scholar
  38. 38.
    Hristov M, Erl W, Weber PC (2003) Endothelial progenitor cells: isolation and characterization. Trends Cardiovasc Med 13(5):201–206PubMedCrossRefGoogle Scholar
  39. 39.
    Lin Y, Weisdorf DJ, Solovey A, Hebbel RP (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105(1):71–77PubMedCrossRefGoogle Scholar
  40. 40.
    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 PubMedGoogle Scholar
  41. 41.
    Bahlmann FH, De Groot K, Spandau JM, Landry AL, Hertel B, Duckert T, Boehm SM, Menne J, Haller H, Fliser D (2004) Erythropoietin regulates endothelial progenitor cells. Blood 103(3):921–926. doi:10.1182/blood-2003-04-12842003-04-1284 PubMedCrossRefGoogle Scholar
  42. 42.
    Balestrieri ML, Rienzo M, Felice F, Rossiello R, Grimaldi V, Milone L, Casamassimi A, Servillo L, Farzati B, Giovane A, Napoli C (2008) High glucose downregulates endothelial progenitor cell number via SIRT1. Biochim Biophys Acta 1784(6):936–945. doi:10.1016/j.bbapap.2008.03.004 PubMedCrossRefGoogle Scholar
  43. 43.
    Balestrieri ML, Schiano C, Felice F, Casamassimi A, Balestrieri A, Milone L, Servillo L, Napoli C (2008) Effect of low doses of red wine and pure resveratrol on circulating endothelial progenitor cells. J Biochem 143(2):179–186. doi:10.1093/jb/mvm209 PubMedCrossRefGoogle Scholar
  44. 44.
    Biancone L, Cantaluppi V, Duo D, Deregibus MC, Torre C, Camussi G (2004) Role of L-selectin in the vascular homing of peripheral blood-derived endothelial progenitor cells. J Immunol 173(8):5268–5274PubMedGoogle Scholar
  45. 45.
    Chavakis E, Aicher A, Heeschen C, Sasaki K, Kaiser R, El Makhfi N, Urbich C, Peters T, Scharffetter-Kochanek K, Zeiher AM, Chavakis T, Dimmeler S (2005) Role of beta2-integrins for homing and neovascularization capacity of endothelial progenitor cells. J Exp Med 201(1):63–72PubMedCrossRefGoogle Scholar
  46. 46.
    Chavakis E, Hain A, Vinci M, Carmona G, Bianchi ME, Vajkoczy P, Zeiher AM, Chavakis T, Dimmeler S (2007) High-mobility group box 1 activates integrin-dependent homing of endothelial progenitor cells. Circ Res 100(2):204–212PubMedCrossRefGoogle Scholar
  47. 47.
    Chen J, Wang X, Zhu J, Shang Y, Guo X, Sun J (2004) Effects of ginkgo biloba extract on number and activity of endothelial progenitor cells from peripheral blood. J Cardiovasc Pharmacol 43(3):347–352PubMedCrossRefGoogle Scholar
  48. 48.
    Chen JZ, Zhang FR, Tao QM, Wang XX, Zhu JH (2004) Number and activity of endothelial progenitor cells from peripheral blood in patients with hypercholesterolaemia. Clin Sci (Lond) 107(3):273–280. doi:10.1042/CS20030389CS20030389 CrossRefGoogle Scholar
  49. 49.
    Chen YH, Lin SJ, Lin FY, Wu TC, Tsao CR, Huang PH, Liu PL, Chen YL, Chen JW (2007) High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms. Diabetes 56(6):1559–1568. doi:10.2337/db06-1103 PubMedCrossRefGoogle Scholar
  50. 50.
    Choi JH, Hur J, Yoon CH, Kim JH, Lee CS, Youn SW, Oh IY, Skurk C, Murohara T, Park YB, Walsh K, Kim HS (2004) Augmentation of therapeutic angiogenesis using genetically modified human endothelial progenitor cells with altered glycogen synthase kinase-3beta activity. J Biol Chem 279(47):49430–49438. doi:10.1074/jbc.M402088200 PubMedCrossRefGoogle Scholar
  51. 51.
    Dernbach E, Urbich C, Brandes RP, Hofmann WK, Zeiher AM, Dimmeler S (2004) Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress. Blood 104(12):3591–3597. doi:10.1182/blood-2003-12-4103 PubMedCrossRefGoogle Scholar
  52. 52.
    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):391–397PubMedGoogle Scholar
  53. 53.
    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 PubMedCrossRefGoogle Scholar
  54. 54.
    Kalka C, Masuda H, Takahashi T, Gordon R, Tepper O, Gravereaux E, Pieczek A, Iwaguro H, Hayashi SI, Isner JM, Asahara T (2000) Vascular endothelial growth factor (165) gene transfer augments circulating endothelial progenitor cells in human subjects. Circ Res 86(12):1198–1202PubMedCrossRefGoogle Scholar
  55. 55.
    Kalka C, Tehrani H, Laudenberg B, Vale PR, Isner JM, Asahara T, Symes JF (2000) VEGF gene transfer mobilizes endothelial progenitor cells in patients with inoperable coronary disease. Ann Thorac Surg 70(3):829–834PubMedCrossRefGoogle Scholar
  56. 56.
    Leshem-Lev D, Omelchenko A, Perl L, Kornowski R, Battler A, Lev EI (2010) Exposure to platelets promotes functional properties of endothelial progenitor cells. J Thromb Thrombolysis. doi:10.1007/s11239-010-0514-0 PubMedGoogle Scholar
  57. 57.
    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(22):2781–2786PubMedCrossRefGoogle Scholar
  58. 58.
    Yodoi Y, Sasahara M, Kameda T, Yoshimura N, Otani A (2007) Circulating hematopoietic stem cells in patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 48(12):5464–5472. doi:10.1167/iovs.07-0093 PubMedCrossRefGoogle Scholar
  59. 59.
    Gensch C, Clever YP, Werner C, Hanhoun M, Bohm M, Laufs U (2007) The PPAR-gamma agonist pioglitazone increases neoangiogenesis and prevents apoptosis of endothelial progenitor cells. Atherosclerosis 192(1):67–74. doi:10.1016/j.atherosclerosis.2006.06.026 PubMedCrossRefGoogle Scholar
  60. 60.
    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):3115–3121PubMedCrossRefGoogle Scholar
  61. 61.
    Ritter MR, Banin E, Moreno SK, Aguilar E, Dorrell MI, Friedlander M (2006) Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy. J Clin Invest 116(12):3266–3276PubMedCrossRefGoogle Scholar
  62. 62.
    Yoon CH, Hur J, Oh IY, Park KW, Kim TY, Shin JH, Kim JH, Lee CS, Chung JK, Park YB, Kim HS (2006) Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells. Arterioscler Thromb Vasc Biol 26(5):1066–1072PubMedCrossRefGoogle Scholar
  63. 63.
    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):5002–5012PubMedGoogle Scholar
  64. 64.
    Wang XR, Zhang MW, Chen DD, Zhang Y, Chen AF (2011) AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese superoxide dismutase induction in type 1 diabetes. Am J Physiol Endocrinol Metab 300(6):E1135–E1145. doi:10.1152/ajpendo.00001.2011 PubMedCrossRefGoogle Scholar
  65. 65.
    Leong KG, Wang BE, Johnson L, Gao WQ (2008) Generation of a prostate from a single adult stem cell. Nature 456(7223):804–808. doi:10.1038/nature07427 PubMedCrossRefGoogle Scholar
  66. 66.
    Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I (2004) Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem 279(12):11384–11391. doi:10.1074/jbc.M310822200 PubMedCrossRefGoogle Scholar
  67. 67.
    Xiao Q, Zeng L, Zhang Z, Hu Y, Xu Q (2007) Stem cell-derived Sca-1+ progenitors differentiate into smooth muscle cells, which is mediated by collagen IV-integrin alpha1/beta1/alphav and PDGF receptor pathways. American journal of physiology Cell physiology 292(1):C342–C352. doi:10.1152/ajpcell.00341.2006 PubMedCrossRefGoogle Scholar
  68. 68.
    Awad O, Jiao C, Ma N, Dunnwald M, Schatteman GC (2005) Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors. Stem Cells 23(4):575–583. doi:10.1634/stemcells.2004-0185 PubMedCrossRefGoogle Scholar
  69. 69.
    Thum T, Fraccarollo D, Galuppo P, Tsikas D, Frantz S, Ertl G, Bauersachs J (2006) Bone marrow molecular alterations after myocardial infarction: impact on endothelial progenitor cells. Cardiovasc Res 70(1):50–60. doi:10.1016/j.cardiores.2006.01.002 PubMedCrossRefGoogle Scholar
  70. 70.
    Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT, Ingram DA (2007) Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 109(5):1801–1809PubMedCrossRefGoogle Scholar
  71. 71.
    Liew A, Barry F, O'Brien T (2006) Endothelial progenitor cells: diagnostic and therapeutic considerations. Bioessays 28(3):261–270. doi:10.1002/bies.20372 PubMedCrossRefGoogle Scholar
  72. 72.
    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):3106–3112PubMedGoogle Scholar
  73. 73.
    Gulati R, Jevremovic D, Peterson TE, Chatterjee S, Shah V, Vile RG, Simari RD (2003) Diverse origin and function of cells with endothelial phenotype obtained from adult human blood. Circ Res 93(11):1023–1025PubMedCrossRefGoogle Scholar
  74. 74.
    Yeh ET, Zhang S, Wu HD, Korbling M, Willerson JT, Estrov Z (2003) Transdifferentiation of human peripheral blood CD34+ −enriched cell population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo. Circulation 108(17):2070–2073PubMedCrossRefGoogle Scholar
  75. 75.
    Wang QR, Yan Y, Wang BH, Li WM, Wolf NS (1998) Long-term culture of murine bone-marrow-derived endothelial cells. Vitro Cell Dev Biol Anim 34(6):443–446CrossRefGoogle Scholar
  76. 76.
    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):841–849PubMedGoogle Scholar
  77. 77.
    Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MA, Werb Z, Rafii S (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell 109(5):625–637PubMedCrossRefGoogle Scholar
  78. 78.
    Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C, Kearney M, Chen D, Symes JF, Fishman MC, Huang PL, Isner JM (1998) Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 101(11):2567–2578PubMedCrossRefGoogle Scholar
  79. 79.
    Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18(14):3964–3972PubMedCrossRefGoogle Scholar
  80. 80.
    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 45–37PubMedCrossRefGoogle Scholar
  81. 81.
    Rabbany SY, Heissig B, Hattori K, Rafii S (2003) Molecular pathways regulating mobilization of marrow-derived stem cells for tissue revascularization. Trends Mol Med 9(3):109–117PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Daniel Barthelmes
    • 1
  • Mohammad R. Irhimeh
    • 1
  • Mark C. Gillies
    • 1
  • Ling Zhu
    • 1
  • Weiyong Shen
    • 1
  1. 1.Save Sight Institute, Sydney Hospital and Sydney Eye HospitalThe University of SydneySydneyAustralia
  2. 2.Save Sight Institute, Sydney Hospital and Sydney Eye HospitalThe University of SydneySydneyAustralia

Personalised recommendations