Skip to main content
SpringerLink
Log in

Biophysical Properties of Scaffolds Modulate Human Blood Vessel Formation from Circulating Endothelial Colony-Forming Cells

  • Chapter
  • First Online:
Biophysical Regulation of Vascular Differentiation and Assembly

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

A functional vascular system forms early in development and is continually remodeled throughout the life of the organism. Impairment to the regeneration or repair of this system leads to tissue ischemia, dysfunction, and disease. The process of vascular formation and remodeling is complex, relying on local microenvironmental cues, cytokine signaling, and multiple cell types to function properly. Tissue engineering strategies have attempted to exploit these mechanisms to develop functional vascular networks for the generation of artificial tissues and therapeutic strategies to restore tissue homeostasis. The success of these strategies requires the isolation of appropriate progenitor cell sources which are straightforward to obtain, display high proliferative potential, and demonstrate an ability to form functional vessels. Several populations are of interest including endothelial colony-forming cells, a subpopulation of endothelial progenitor cells. Additionally, the development of scaffolds to deliver and support progenitor cell survival and function is crucial for the formation of functional vascular networks. The composition and biophysical properties of these scaffolds have been shown to modulate endothelial cell behavior and vessel formation. However, further investigation is needed to better understand how these mechanical properties and biophysical properties impact vessel formation. Additionally, several other cell populations are involved in neoangiogenesis and formation of tissue parenchyma and an understanding of the potential impact of these cell populations on the biophysical properties of scaffolds will also be needed to advance these strategies. This chapter examines how the biophysical properties of matrix scaffolds can influence vessel formation and remodeling and, in particular, the impact on in vivo human endothelial progenitor cell vessel formation.

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 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Abbreviations

αSMA:

Alpha smooth muscle actin

AcLDL:

Acetylated low-density lipoprotein

CAC:

Circulating angiogenic cells

CFU-HILL:

Colony forming unit-HILL cells

ECFC:

Endothelial colony forming cells

ECM:

Extracellular matrix

EPC:

Endothelial progenitor cell

FGF:

Fibroblast growth factor

GATA2:

GATA binding protein 2

hESC:

Human embryonic stem cell

HMVEC:

Human microvascular endothelial cell

HUVEC:

Human umbilical vein endothelial cell

iPSC:

Induced pluripotent stem cell

MMP:

Matrix metalloproteinase

MSC:

Mesenchymal stem cell

MT1-MMP:

Membrane type 1 MMP

PDMS:

Polydimethylsiloxane

PEG:

Polyethylene glycol

PGA:

Polyglycolic acid

PLA:

Polylactic acid

PLGA:

Poly-(lactide-co-glycolide)

PLLA:

Poly-l-lactic acid

RGD:

Arginine–glycine–aspartic acid

UEA-1:

Ulex europaeus agglutinin-1

VEGF:

Vascular endothelial growth factor

VEGFR2:

VEGF receptor 2

VWF:

Von Willebrand factor

References

  1. Conway EM, Collen D, Carmeliet P. Molecular mechanisms of blood vessel growth. Cardiovasc Res. 2001;49:507–521.

    Article  Google Scholar 

  2. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407: 249–257.

    Article  Google Scholar 

  3. Jain RK, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue.Nat Biotechnol. 2005;23:821–823.

    Article  Google Scholar 

  4. Kawamoto A, Asahara T. Role of progenitor endothelial cells in cardiovascular disease and upcoming therapies. Catheter Cardiovasc Interv. 2007;70:477–484.

    Article  Google Scholar 

  5. Levenberg S. Engineering blood vessels from stem cells: recent advances and applications. Curr Opin Biotechnol. 2005;16:516–523.

    Article  Google Scholar 

  6. Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood. 2007;109:1801–1809.

    Article  Google Scholar 

  7. Au P, Daheron LM, Duda DG, et al. Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vessels. Blood. 2008;111:1302–1305.

    Article  Google Scholar 

  8. Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood. 2007;109:4761–4768.

    Article  Google Scholar 

  9. Schechner JS, Nath AK, Zheng L, et al. In vivo formation of complex microvessels lined by human endothelial cells in an immunodeficient mouse. Proc Natl Acad Sci USA. 2000;97:9191–9196.

    Article  ADS  Google Scholar 

  10. Shepherd BR, Enis DR, Wang F, Suarez Y, Pober JS, Schechner JS. Vascularization and engraftment of a human skin substitute using circulating progenitor cell-derived endothelial cells. FASEB J. 2006;20:1739–1741.

    Article  Google Scholar 

  11. Ng CP, Helm CL, Swartz MA. Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. Microvasc Res. 2004;68:258–264.

    Article  Google Scholar 

  12. Luong E, Gerecht S. Stem cells and scaffolds for vascularizing engineered tissue constructs. Adv Biochem Eng Biotechnol. 2009;114:129–172.

    Google Scholar 

  13. Koike N, Fukumura D, Gralla O, Au P, Schechner JS, Jain RK. Tissue engineering: creation of long-lasting blood vessels. Nature. 2004;428:138–139.

    Article  ADS  Google Scholar 

  14. Lesman A, Habib M, Caspi O, et al. Transplantation of a tissue-engineered human vascularized cardiac muscle. Tissue Eng Part A. 2010;16:115–125.

    Article  Google Scholar 

  15. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275:964–967.

    Article  Google Scholar 

  16. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89:e1–e7.

    Article  Google Scholar 

  17. Hill JM, Zalos G, Halcox JPJ, et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600.

    Article  Google Scholar 

  18. Schatteman GC, Dunnwald M, Jiao C. Biology of bone marrow-derived endothelial cell precursors. Am J Physiol Heart Circ Physiol. 2007;292:H1–H18.

    Article  Google Scholar 

  19. Prater DN, Case J, Ingram DA, Yoder MC. Working hypothesis to redefine endothelial progenitor cells. Leukemia. 2007;21:1141–1149.

    Article  Google Scholar 

  20. Lin Y, Weisdorf DJ, Solovey A, Hebbel RP. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest. 2000;105:71–77.

    Article  Google Scholar 

  21. Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104:2752–2760.

    Article  Google Scholar 

  22. Peichev M, Naiyer AJ, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors. Blood. 2000;95:952–958.

    Google Scholar 

  23. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol. 1995;11:73–91.

    Article  Google Scholar 

  24. Hirschi KK, Ingram DA, Yoder MC. Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2008;28:1584–1595.

    Article  Google Scholar 

  25. Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation. 2001;103:2885–2890.

    Article  Google Scholar 

  26. Rehman J, Li J, Orschell CM, March KL. Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation. 2003;107:1164–1169.

    Article  Google Scholar 

  27. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci USA. 2000;97:3422–3427.

    Article  ADS  Google Scholar 

  28. Asosingh K, Aldred MA, Vasanji A, et al. Circulating angiogenic precursors in idiopathic pulmonary arterial hypertension. Am J Pathol. 2008;172:615–627.

    Article  Google Scholar 

  29. Hur J, Yoon C-H, Kim H-S, et al. Characterization of two types of endothelial progenitor cells and their different contributions to neovasculogenesis. Arterioscler Thromb Vasc Biol. 2004;24:288–293.

    Article  Google Scholar 

  30. Stratman AN, Malotte KM, Mahan RD, Davis MJ, Davis GE. Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood. 2009;114:5091–5101.

    Article  Google Scholar 

  31. Gerecht-Nir S, Ziskind A, Cohen S, Itskovitz-Eldor J. Human embryonic stem cells as an in vitro model for human vascular development and the induction of vascular differentiation. Lab Invest. 2003;83:1811–1820.

    Article  Google Scholar 

  32. Wang ZZ, Au P, Chen T, et al. Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo. Nat Biotechnol. 2007;25:317–318.

    Article  Google Scholar 

  33. Ferreira LS, Gerecht S, Shieh HF, et al. Vascular progenitor cells isolated from human embryonic stem cells give rise to endothelial and smooth muscle like cells and form vascular networks in vivo. Circ Res. 2007;101:286–294.

    Article  Google Scholar 

  34. Lees JG, Lim SA, Croll T, et al. Transplantation of 3D scaffolds seeded with human embryonic stem cells: biological features of surrogate tissue and teratoma-forming potential. Regen Med. 2007;2:289–300.

    Article  Google Scholar 

  35. Park IH, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell. 2008;134:877–886.

    Article  Google Scholar 

  36. Ebert AD, Yu J, Rose FF, Jr, et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2009;457:277–280.

    Article  ADS  Google Scholar 

  37. Tateishi K, He J, Taranova O, Liang G, D’Alessio AC, Zhang Y. Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem. 2008;283:31601–31607.

    Article  Google Scholar 

  38. Maehr R, Chen S, Snitow M, et al. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci USA. 2009;106:15768–15773.

    Article  ADS  Google Scholar 

  39. Choi KD, Yu J, Smuga-Otto K, et al. Hematopoietic and endothelial differentiation of human induced pluripotent stem cells. Stem Cells. 2009;27:559–567.

    Google Scholar 

  40. Taura D, Sone M, Homma K, et al. Induction and isolation of vascular cells from human induced pluripotent stem cells – brief report. Arterioscler Thromb Vasc Biol. 2009;29:1100–1103.

    Article  Google Scholar 

  41. Pedersen JA, Swartz MA. Mechanobiology in the third dimension. Ann Biomed Eng. 2005;33:1469–1490.

    Article  Google Scholar 

  42. Sieminski AL, Was AS, Kim G, Gong H, Kamm RD. The stiffness of three-dimensional ionic self-assembling peptide gels affects the extent of capillary-like network formation. Cell Biochem Biophys. 2007;49:73–83.

    Article  Google Scholar 

  43. Hanjaya-Putra D, Yee J, Ceci D, Truitt R, Yee D, Gerecht S. Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells. J Cell Mol Med. 2010;14:2436–2447.

    Google Scholar 

  44. Silva EA, Kim E-S, Kong HJ, Mooney DJ. Material-based deployment enhances efficacy of endothelial progenitor cells. Proc Natl Acad Sci USA. 2008;105:14347–14352.

    Article  ADS  Google Scholar 

  45. Zeugolis DI, Paul RG, Attenburrow G. Factors influencing the properties of reconstituted collagen fibers prior to self-assembly: animal species and collagen extraction method. J Biomed Mater Res A. 2008;86A:892–904.

    Article  Google Scholar 

  46. Kreger ST, Voytik-Harbin SL. Hyaluronan concentration within a 3D collagen matrix modulates matrix viscoelasticity, but not fibroblast response. Matrix Biol. 2009;28:336–346.

    Article  Google Scholar 

  47. Zeugolis DI, Paul GR, Attenburrow G. Cross-linking of extruded collagen fibers – A biomimetic three-dimensional scaffold for tissue engineering applications. J Biomed Mater Res A. 2009;89:895–908.

    Google Scholar 

  48. Guidry C, Grinnell F. Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts. J Cell Sci. 1985;79:67–81.

    Google Scholar 

  49. Guidry C. Contraction of hydrated collagen gels by fibroblasts: evidence for two mechanisms by which collagen fibrils are stabilized. Collagen Rel Res. 1986;6:515–529.

    Google Scholar 

  50. Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993;260:1124–1127.

    Article  ADS  Google Scholar 

  51. Rupp PA, Little CD. Integrins in vascular development. Circ Res. 2001;89:566–572.

    Article  Google Scholar 

  52. Galbraith CG, Sheetz MP. Forces on adhesive contacts affect cell function. Curr Opin Cell Biol. 1998;10:566–571.

    Article  Google Scholar 

  53. Ingber D. In search of cellular control: signal transduction in context. J Cell Biochem. 1998;72:232–237.

    Article  Google Scholar 

  54. Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Geometric control of cell life and death. Science. 1997;276:1425–1428.

    Article  Google Scholar 

  55. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6:483–495.

    Article  Google Scholar 

  56. Ruiz SA, Chen CS. Emergence of patterned stem cell differentiation within multicellular structures. Stem Cells. 2008;26:2921–2927.

    Article  Google Scholar 

  57. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126:677–689.

    Article  Google Scholar 

  58. Folkman J, Haudenschild C. Angiogenesis in vitro. Nature. 1980;288:551–556.

    Article  ADS  Google Scholar 

  59. Vernon RB, Sage EH. Between molecules and morphology. Extracellular matrix and creation of vascular form. Am J Pathol. 1995;147:873–883.

    Google Scholar 

  60. Ingber DE, Madri JA, Folkman J. Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion. In Vitro Cell Dev Biol. 1987;23:387–394.

    Article  Google Scholar 

  61. Montesano R, Vassalli JD, Baird A, Guillemin R, Orci L. Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci USA. 1986;83:7297–7301.

    Article  ADS  Google Scholar 

  62. Ingber DE, Folkman J. Mechanochemical switching between growth and differentiation during fibroblast growth factor-stimulated angiogenesis in vitro: role of extracellular matrix. J Cell Biol. 1989;109:317–330.

    Article  Google Scholar 

  63. Davis GE, Camarillo CW. An [alpha]2[beta]1 integrin-dependent pinocytic mechanism involving intracellular vacuole formation and coalescence regulates capillary lumen and tube formation in three-dimensional collagen matrix. Exp Cell Res. 1996;224:39–51.

    Article  Google Scholar 

  64. Kanzawa S, Endo H, Shioya N. Improved in vitro angiogenesis model by collagen density reduction and the use of type III collagen. Ann Plast Surg. 1993;30:244–251.

    Article  Google Scholar 

  65. Ment L, Stewart W, Scaramuzzino D, Madri J. An in vitro three-dimensional coculture model of cerebral microvascular angiogenesis and differentiation. In Vitro Cell Dev Biol Anim. 1997;33:684–691.

    Article  Google Scholar 

  66. Ilan N, Mahooti S, Madri JA. Distinct signal transduction pathways are utilized during the tube formation and survival phases of in vitro angiogenesis. J Cell Sci. 1998;111:3621–3631.

    Google Scholar 

  67. Korff T, Augustin HG. Tensional forces in fibrillar extracellular matrices control directional capillary sprouting. J Cell Sci. 1999;112(Pt 19):3249–3258.

    Google Scholar 

  68. Salazar R, Bell SE, Davis GE. Coordinate Induction of the actin cytoskeletal regulatory proteins gelsolin, vasodilator-stimulated phosphoprotein, and profilin during capillary morphogenesis in vitro. Exp Cell Res. 1999;249:22–32.

    Article  Google Scholar 

  69. Vernon RB, Sage EH. A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices. Microvasc Res. 1999;57:118–133.

    Article  Google Scholar 

  70. Yang S, Graham J, Kahn JW, Schwartz EA, Gerritsen ME. Functional roles for PECAM-1 (CD31) and VE-Cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels. Am J Pathol. 1999;155:887–895.

    Article  Google Scholar 

  71. Sieminski AL, Hebbel RP, Gooch KJ. The relative magnitudes of endothelial force generation and matrix stiffness modulate capillary morphogenesis in vitro. Exp Cell Res. 2004;297:574–584.

    Article  Google Scholar 

  72. Koh W, Mahan RD, Davis GE. Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and Par3, and PKC-dependent signaling. J Cell Sci. 2008;121:989–1001.

    Article  Google Scholar 

  73. Matsumura T, Wolff K, Petzelbauer P. Endothelial cell tube formation depends on cadherin 5 and CD31 interactions with filamentous actin. J Immunol. 1997;158:3408–3416.

    Google Scholar 

  74. Stratman AN, Saunders WB, Sacharidou A, et al. Endothelial cell lumen and vascular guidance tunnel formation requires MT1-MMP-dependent proteolysis in 3-dimensional collagen matrices. Blood. 2009;114:237–247.

    Article  Google Scholar 

  75. Melero-Martin JM, De Obaldia ME, Kang SY, et al. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res. 2008;103:194–202.

    Article  Google Scholar 

  76. Au P, Tam J, Fukumura D, Jain RK. Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood. 2008;111:4551–4558.

    Article  Google Scholar 

  77. Yamamura N, Sudo R, Ikeda M, Tanishita K. Effects of the mechanical properties of collagen gel on the in vitro formation of microvessel networks by endothelial cells. Tissue Eng. 2007;13:1443–1453.

    Article  Google Scholar 

  78. Critser PJ, Kreger ST, Voytik-Harbin SL, Yoder MC. Collagen matrix physical properties modulate endothelial colony forming cell derived vessels in vivo. Microvasc Res. 2010;80:23–30.

    Article  Google Scholar 

  79. Mammoto A, Connor KM, Mammoto T, et al. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature. 2009;457:1103–1108.

    Article  ADS  Google Scholar 

  80. Sasagawa T, Shimizu T, Sekiya S, et al. Design of prevascularized three-dimensional cell-dense tissues using a cell sheet stacking manipulation technology. Biomaterials. 2010;31:1646–1654.

    Article  Google Scholar 

  81. Caspi O, Lesman A, Basevitch Y, et al. Tissue engineering of vascularized cardiac muscle from human embryonic stem cells. Circ Res. 2007;100:263–272.

    Article  Google Scholar 

  82. Kannan RY, Salacinski HJ, Sales K, Butler P, Seifalian AM. The roles of tissue engineering and vascularisation in the development of micro-vascular networks: a review. Biomaterials. 2005;26:1857–1875.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the Riley Children’s Foundation, Indianapolis, Indiana and the National Institutes of Health Grant F30-HL096350-01.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Indiana University School of Medicine, 1044 West Walnut Street, R4-W125A, Indianapolis, IN, 46202, USA

    Mervin C. Yoder

  2. Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA

    Mervin C. Yoder

  3. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA

    Mervin C. Yoder

Authors
  1. Paul J. Critser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mervin C. Yoder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mervin C. Yoder .

Editor information

Editors and Affiliations

  1. Department of Mechanical Engineering, The Johns Hopkins University, North Charles Street 3400, Baltimore, 21218-2682, Maryland, USA

    Sharon Gerecht

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Critser, P.J., Yoder, M.C. (2011). Biophysical Properties of Scaffolds Modulate Human Blood Vessel Formation from Circulating Endothelial Colony-Forming Cells. In: Gerecht, S. (eds) Biophysical Regulation of Vascular Differentiation and Assembly. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7835-6_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-7835-6_5

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-7834-9

  • Online ISBN: 978-1-4419-7835-6

  • eBook Packages: Physics and AstronomyPhysics and Astronomy (R0)

Publish with us

Policies and ethics

Search

Navigation