Skip to main content
SpringerLink
Log in

Therapeutic Angiogenesis in Regenerative Medicine

  • Reference work entry
  • First Online:
Vascularization for Tissue Engineering and Regenerative Medicine

Part of the book series: Reference Series in Biomedical Engineering ((TIENRE))

Abstract

A vascular network along with a sufficient blood supply is not only essential for physiological maintenance of tissue viability but is also a prerequisite for any approaches in regenerative medicine. Previously it was thought that therapeutic angiogenesis can effectively be realized simply by the local release of angiogenic growth factors from matrices, but a more complex correlation between the spatial and temporal distribution of factors and the microenvironmental tissue demands has emerged. After introducing the different kinds and steps of angiogenesis, the review will highlight the key issues of therapeutic angiogenesis and various opportunities for recombinant growth factor delivery strategies. The modifications of binding and release kinetics of angiogenic factors from delivery platforms will be discussed in detail in order to achieve a mature and functional vascular network.

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 439.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
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

Similar content being viewed by others

References

  • Al-Dosari MS, Gao X (2009) Nonviral gene delivery: principle, limitations, and recent progress. AAPS J 11:671–681

    Article  Google Scholar 

  • Anderson EM, Silva EA, Hao Y, Martinick KD, Vermillion SA, Stafford AG, Doherty EG, Wang L, Doherty EJ, Grossman PM, Mooney DJ (2017) VEGF and IGF delivered from alginate hydrogels promote stable perfusion recovery in ischemic hind limbs of aged mice and young rabbits. J Vasc Res 54:288–298

    Article  Google Scholar 

  • Annex BH (2013) Therapeutic angiogenesis for critical limb ischaemia. Nat Rev Cardiol 10:387–396

    Article  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 (80) 275:964–967

    Article  Google Scholar 

  • Bae H, Puranik AS, Gauvin R, Edalat F, Carrillo-Conde B, Peppas NA, Khademhosseini A (2012) Building vascular networks. Sci Transl Med 4:160ps23–160ps23

    Article  Google Scholar 

  • Banfi A, von Degenfeld G, Blau HM (2005) Critical role of microenvironmental factors in angiogenesis. Curr Atheroscler Rep 7:227–234

    Article  Google Scholar 

  • Banfi A, von Degenfeld G, Gianni-Barrera R, Reginato S, Merchant MJ, McDonald DM, Blau HM (2012) Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. FASEB J 26:2486–2497

    Article  Google Scholar 

  • Benjamin EJ, Blaha MJ, Chiuve SE et al (2017) Heart disease and stroke statistics 2017 update: a report from the American Heart Association. Circulation 136:e196

    Google Scholar 

  • Benjamin EJ et al (2019) Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. https://doi.org/10.1161/CIR.0000000000000659. PMID: 30700139

  • Berlin DH, Platz A, Berlin D-, Höpfner M, Noble F, Medizin MM, Secomb TW. NIH Public Access. 2011;10:587–593

    Google Scholar 

  • Burri PH, Djonov V (2002) Intussusceptive angiogenesis--the alternative to capillary sprouting. Mol Asp Med 23:S1–S27

    Article  Google Scholar 

  • Capila I, Linhardt RJ (2002) Heparin-protein interactions. Angew Chem Int Ed Engl 41:391–412

    Article  Google Scholar 

  • Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  Google Scholar 

  • Carmeliet P, De Smet F, Loges S, Mazzone M (2009) Branching morphogenesis and antiangiogenesis candidates: tip cells lead the way. Nat Rev Clin Oncol 6:315–326

    Article  Google Scholar 

  • Chen RR, Mooney DJ (2003) Polymeric growth factor delivery strategies for tissue engineering. Pharm Res 20:1103–1112

    Article  Google Scholar 

  • De Laporte L, Rice JJ, Tortelli F, Hubbell JA, Tenascin C (2013) Promiscuously binds growth factors via its fifth fibronectin type III-like domain. PLoS One 8:e62076

    Article  Google Scholar 

  • De Spiegelaere W, Casteleyn C, Van Den Broeck W, Plendl J, Bahramsoltani M, Simoens P, Djonov V, Cornillie P (2012) Intussusceptive angiogenesis: a biologically relevant form of angiogenesis. J Vasc Res 49:390–404

    Article  Google Scholar 

  • Dor Y, Djonov V, Abramovitch R, Itin A, Fishman GI, Carmeliet P, Goelman G, Keshets E (2002) Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. EMBO J 21:1939–1947

    Article  Google Scholar 

  • Dragneva G, Korpisalo P, Yla-Herttuala S (2013) Promoting blood vessel growth in ischemic diseases: challenges in translating preclinical potential into clinical success. Dis Model Mech 6:312–322

    Google Scholar 

  • Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337–4351

    Article  Google Scholar 

  • Edelstein ML, Abedi MR, Wixon J (2007) Gene therapy clinical trials worldwide to 2007--an update. J Gene Med 9:833–842

    Article  Google Scholar 

  • Egginton S, Zhou AL, Brown MD, Hudlická O (2001) Unorthodox angiogenesis in skeletal muscle. Cardiovasc Res 49:634–646

    Article  Google Scholar 

  • Ehrbar M, Djonov VG, Schnell C, Tschanz SA, Martiny-Baron G, Schenk U, Wood J, Burri PH, Hubbell JA, Zisch AH (2004) Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circ Res 94:1124–1132

    Article  Google Scholar 

  • Ehrbar M, Rizzi SC, Hlushchuk R, Djonov V, Zisch AH, Hubbell JA, Weber FE, Lutolf MP (2007) Enzymatic formation of modular cell-instructive fibrin analogs for tissue engineering. Biomaterials 28:3856–3866

    Article  Google Scholar 

  • Ehrbar M, Zeisberger SM, Raeber GP, Hubbell JA, Schnell C, Zisch AH (2008) The role of actively released fibrin-conjugated VEGF for VEGF receptor 2 gene activation and the enhancement of angiogenesis. Biomaterials 29:1720–1729

    Article  Google Scholar 

  • Ellertsdóttir E, Lenard A, Blum Y, Krudewig A, Herwig L, Affolter M, Belting HG (2010) Vascular morphogenesis in the zebrafish embryo. Dev Biol 341:56–65

    Article  Google Scholar 

  • Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C (2010) Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116:829–840

    Article  Google Scholar 

  • Gaengel K, Genové G, Armulik A, Betsholtz C (2009) Endothelial-mural cell signaling in vascular development and angiogenesis. Arterioscler Thromb Vasc Biol 29:630–638

    Article  Google Scholar 

  • Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163–1177

    Article  Google Scholar 

  • Giacca M, Zacchigna S (2012) VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther 19:622–629

    Article  Google Scholar 

  • Gianni-Barrera R, Trani M, Reginato S, Banfi A (2011) To sprout or to split? VEGF, Notch and vascular morphogenesis. Biochem Soc Trans 39:1644–1648

    Article  Google Scholar 

  • Gianni-Barrera R, Trani M, Fontanellaz C, Heberer M, Djonov V, Hlushchuk R, Banfi A (2013) VEGF over-expression in skeletal muscle induces angiogenesis by intussusception rather than sprouting. Angiogenesis 16:123–136

    Article  Google Scholar 

  • Hanahan D (1997) Signaling vascular morphogenesis and maintenance. Science (80- ) 277:48–50

    Article  Google Scholar 

  • Heil M, Schaper W (2005) Cellular mechanisms of arteriogenesis. EXS 94:181–191

    Google Scholar 

  • Heil M, Eitenmüller I, Schmitz-Rixen T, Schaper W (2006) Arteriogenesis versus angiogenesis: similarities and differences. J Cell Mol Med 10:45–55

    Article  Google Scholar 

  • Hellström M, Kalén M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-β in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055

    Article  Google Scholar 

  • Hellström M, Phng L-K, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson A-K, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela-Arispe ML, Kalén M, Gerhardt H, Betsholtz C (2007) Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445:776–780

    Article  Google Scholar 

  • Herwig L, Blum Y, Krudewig A, Ellertsdottir E, Lenard A, Belting HG, Affolter M (2011) Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo. Curr Biol 21:1942–1948

    Article  Google Scholar 

  • Hynes RO (2009) The extracellular matrix: not just pretty fibrils. Science (80- ) 326:1216–1219

    Article  Google Scholar 

  • Iruela-Arispe ML, Davis GE (2009) Cellular and molecular mechanisms of vascular lumen formation. Dev Cell 16:222–231

    Article  Google Scholar 

  • Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693

    Article  Google Scholar 

  • Johnson PC, Mikos AG, Fisher JP, Jansen JA (2007) Strategic directions in tissue engineering. Tissue Eng 13:2827–2837

    Article  Google Scholar 

  • Jones N, Iljin K, Dumont DJ, Alitalo K (2001) Tie receptors: new modulators of angiogenic and lymphangiogenic responses. Nat Rev Mol Cell Biol 2:257–267

    Article  Google Scholar 

  • Karvinen H, Ylä-Herttuala S (2010) New aspects in vascular gene therapy. Curr Opin Pharmacol 10:208–211

    Article  Google Scholar 

  • Kässmeyer S, Plendl J, Custodis P, Bahramsoltani M (2009) New insights in vascular development: vasculogenesis and endothelial progenitor cells. Anat Histol Embryol 38:1–11

    Article  Google Scholar 

  • Lee KY, Mooney DJ (2001) Hydrogels for tissue engineering. Chem Rev 101:1869–1879

    Article  Google Scholar 

  • Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM (2000) VEGF Gene delivery to myocardium deleterious effects of unregulated expression. Circulation 102:898–901

    Article  Google Scholar 

  • Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellström M, Bäckström G, Fredriksson S, Landegren U, Nyström HC, Bergström G, Dejana E, Östman A, Lindahl P, Betsholtz C (2003) Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 17:1835–1840

    Article  Google Scholar 

  • Lorentz KM, Kontos S, Frey P, Hubbell JA (2011) Engineered aprotinin for improved stability of fibrin biomaterials. Biomaterials 32:430–438

    Article  Google Scholar 

  • Macri L, Silverstein D, Clark RAF (2007) Growth factor binding to the pericellular matrix and its importance in tissue engineering. Adv Drug Deliv Rev 59:1366–1381

    Article  Google Scholar 

  • Makanya AN, Hlushchuk R, Djonov VG (2009) Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling. Angiogenesis 12:113–123

    Article  Google Scholar 

  • Martino MM, Hubbell JA (2010) The 12th-14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J 24:4711–4721

    Google Scholar 

  • Martino MM, Tortelli F, Mochizuki M, Traub S, Ben-David D, Kuhn GA, Muller R, Livne E, Eming SA, Hubbell JA (2011) Engineering the growth factor microenvironment with fibronectin domains to promote wound and bone tissue healing. Sci Transl Med 3:100ra89–100ra89

    Article  Google Scholar 

  • Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA (2013) Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc Natl Acad Sci 110:4563–4568

    Article  Google Scholar 

  • Martino MM, Briquez PS, Guc E, Tortelli F, Kilarski WW, Metzger S, Rice JJ, Kuhn GA, Muller R, Swartz MA, Hubbell JA (2014) Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science (80- ) 343:885–888

    Article  Google Scholar 

  • Martino MM, Brkic S, Bovo E, Burger M, Schaefer DJ, Wolff T, Gürke L, Briquez PS, Larsson HM, Gianni-Barrera R, Hubbell JA, Banfi A (2015) Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine. Front Bioeng Biotechnol 3:45

    Article  Google Scholar 

  • Masaki I (2002) Angiogenic gene therapy for experimental critical limb ischemia: acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2. Circ Res 90:966–973

    Article  Google Scholar 

  • Mintzer MA, Simanek EE (2009) Nonviral vectors for gene delivery. Chem Rev 109:259–302

    Article  Google Scholar 

  • Misteli H, Wolff T, Füglistaler P, Gianni-Barrera R, Gürke L, Heberer M, Banfi A (2010) High-throughput flow cytometry purification of transduced progenitors expressing defined levels of vascular endothelial growth factor induces controlled angiogenesis in vivo. Stem Cells 28:611–619

    Article  Google Scholar 

  • Mittermayr R, Morton T, Hofmann M, Helgerson S, Van Griensven M, Redl H (2008) Sustained (rh)VEGF165 release from a sprayed fibrin biomatrix induces angiogenesis, up-regulation of endogenous VEGF-R2, and reduces ischemic flap necrosis. Wound Repair Regen 16:542–550

    Article  Google Scholar 

  • Mujagic E, Gianni-Barrera R, Trani M, Patel A, Gürke L, Heberer M, Wolff T, Banfi A (2013) Induction of aberrant vascular growth, but not of Normal angiogenesis, by cell-based expression of different doses of human and mouse VEGF is species-dependent. Hum Gene Ther Methods 24:28–37

    Article  Google Scholar 

  • Norgren L, Hiatt WR, Dormandy JA et al (2007) Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 45:S5–S67

    Article  Google Scholar 

  • Ostman A, Andersson M, Betsholtz C, Westermark B, Heldin CH (1991) Identification of a cell retention signal in the B-chain of platelet-derived growth factor and in the long splice version of the A-chain. Cell Regul 2:503–512

    Article  Google Scholar 

  • Ozawa CR, Banfi A, Glazer NL, Thurston G, Springer ML, Kraft PE, McDonald DM, Blau HM (2004) Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest 113:516–527

    Article  Google Scholar 

  • Park JE, Keller GA, Ferrara N (1993) The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 4:1317–1326

    Article  Google Scholar 

  • Pettersson A, Nagy JA, Brown LF, Sundberg C, Morgan E, Jungles S, Carter R, Krieger JE, Manseau EJ, Harvey VS, Eckelhoefer IA, Feng D, Dvorak AM, Mulligan RC, Dvorak HF (2000) Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Investig 80:99–115

    Article  Google Scholar 

  • Phelps EA, Headen DM, Taylor WR, Thulé PM, García AJ (2013) Vasculogenic bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes. Biomaterials 34:4602–4611

    Article  Google Scholar 

  • Potente M, Gerhardt H, Carmeliet P (2011) Basic and therapeutic aspects of angiogenesis. Cell 146:873–887

    Article  Google Scholar 

  • Reginato S, Gianni-Barrera R, Banfi A (2011) Taming of the wild vessel: promoting vessel stabilization for safe therapeutic angiogenesis: figure 1. Biochem Soc Trans 39:1654–1658

    Article  Google Scholar 

  • Ribatti D, Vacca A, Nico B, Roncali L, Dammacco F (2001) Postnatal vasculogenesis. Mech Dev 100:157–163

    Article  Google Scholar 

  • Ribatti D, Nico B, Crivellato E (2009) Morphological and molecular aspects of physiological vascular morphogenesis. Angiogenesis 12:101–111

    Article  Google Scholar 

  • Rissanen TT, Korpisalo P, Markkanen JE, Liimatainen T, Ordén MR, Kholová I, De Goede A, Heikura T, Gröhn OH, Ylä-Herttuala S (2005) Blood flow remodels growing vasculature during vascular endothelial growth factor gene therapy and determines between capillary arterialization and sprouting angiogenesis. Circulation 112:3937–3946

    Article  Google Scholar 

  • Robinson CJ, Stringer SE (2001) The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114:853–865

    Article  Google Scholar 

  • Rouwkema J, Rivron NC, van Blitterswijk CA (2008) Vascularization in tissue engineering. Trends Biotechnol 26:434–441

    Article  Google Scholar 

  • Rufaihah AJ, Johari NA, Vaibavi SR, Plotkin M, Di Thien DT, Kofidis T, Seliktar D (2017) Dual delivery of VEGF and ANG-1 in ischemic hearts using an injectable hydrogel. Acta Biomater 48:58–67

    Article  Google Scholar 

  • Ruhrberg C, Gerhardt H, Golding M, Watson R, Ioannidou S, Fujisawa H, Betsholtz C, Shima DT (2002) Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 16:2684–2698

    Article  Google Scholar 

  • Sacchi V, Mittermayr R, Hartinger J, Martino MM, Lorentz KM, Wolbank S, Hofmann A, Largo RA, Marschall JS, Groppa E, Gianni-Barrera R, Ehrbar M, Hubbell JA, Redl H, Banfi A (2014) Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164. Proc Natl Acad Sci 111:6952–6957

    Article  Google Scholar 

  • Sakiyama-Elbert SE, Hubbell JA (2000) Controlled release of nerve growth factor from a heparin-containing fibrin-based cell ingrowth matrix. J Control Release 69:149–158

    Article  Google Scholar 

  • Sakiyama-Elbert SE, Panitch A, Hubbell JA (2001) Development of growth factor fusion proteins for cell-triggered drug delivery. FASEB J 15:1300–1302

    Article  Google Scholar 

  • Schense JC, Hubbell JA (1999) Cross-linking exogenous bifunctional peptides into fibrin gels with factor XIIIa. Bioconjug Chem 10:75–81

    Article  Google Scholar 

  • Scherberich A, Müller AM, Schäfer DJ, Banfi A, Martin I (2010) Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. J Cell Physiol 225:348–353

    Article  Google Scholar 

  • Schönherr E, Hausser HJ (2000) Extracellular matrix and cytokines: a functional unit. Dev Immunol 7:89–101

    Article  Google Scholar 

  • Schultz GS, Wysocki A (2009) Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 17:153–162

    Article  Google Scholar 

  • Schwarz ER, Speakman MT, Patterson M, Hale SS, Isner JM, Kedes LH, Kloner RA (2000) Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat-angiogenesis and angioma formation. J Am Coll Cardiol 35:1323–1330

    Article  Google Scholar 

  • Sharmin F, McDermott C, Lieberman J, Sanjay A, Khan Y (2017) Dual growth factor delivery from biofunctionalized allografts: sequential VEGF and BMP-2 release to stimulate allograft remodeling. J Orthop Res 35:1086–1095

    Article  Google Scholar 

  • Silva AKA, Richard C, Bessodes M, Scherman D, Merten OW (2009) Growth factor delivery approaches in hydrogels. Biomacromolecules 10:9–18

    Article  Google Scholar 

  • Sims DE (1986) The pericyte-a review. Tissue Cell 18:153–174

    Article  Google Scholar 

  • Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM (1998) VEGF gene delivery to muscle: potential role for vasculogenesis in adults. Mol Cell 2:549–558

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Sundberg C, Nagy JA, Brown LF, Feng D, Eckelhoefer IA, Manseau EJ, Dvorak AM, Dvorak HF (2001) Glomeruloid microvascular proliferation follows adenoviral vascular permeability factor/vascular endothelial growth factor-164 gene delivery. Am J Pathol 158:1145–1160

    Article  Google Scholar 

  • Tafuro S, Ayuso E, Zacchigna S, Zentilin L, Moimas S, Dore F, Giacca M (2009) Inducible adeno-associated virus vectors promote functional angiogenesis in adult organisms via regulated vascular endothelial growth factor expression. Cardiovasc Res 83:663–671

    Article  Google Scholar 

  • Tayalia P, Mooney DJ (2009) Controlled growth factor delivery for tissue engineering. Adv Mater 21:3269–3285

    Article  Google Scholar 

  • Traub S, Morgner J, Martino MM, Höning S, Swartz MA, Wickström SA, Hubbell JA, Eming SA (2013) The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165. Biomaterials 34:5958–5968

    Article  Google Scholar 

  • Upton Z, Cuttle L, Noble A, Kempf M, Topping G, Malda J, Xie Y, Mill J, Harkin DG, Kravchuk O, Leavesley DI, Kimble RM (2008) Vitronectin: growth factor complexes hold potential as a wound therapy approach. J Invest Dermatol 128:1535–1544

    Article  Google Scholar 

  • Vajanto I, Rissanen TT, Rutanen J, Hiltunen MO, Tuomisto TT, Arve K, Närvänen O, Manninen H, Räsänen H, Hippeläinen M, Alhava E, Ylä-Herttuala S (2002) Evaluation of angiogenesis and side effects in ischemic rabbit hindlimbs after intramuscular injection of adenoviral vectors encoding VEGF and LacZ. J Gene Med 4:371–380

    Article  Google Scholar 

  • Villemejane J, Mir LM (2009) Physical methods of nucleic acid transfer: general concepts and applications. Br J Pharmacol 157:207–219

    Article  Google Scholar 

  • von Degenfeld G, Banfi A, Springer ML, Wagner RA, Jacobi J, Ozawa CR, Merchant MJ, Cooke JP, Blau HM (2006) Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. FASEB J 20:2657–2659

    Article  Google Scholar 

  • Ylä-Herttuala S, Markkanen JE, Rissanen TT (2004) Gene therapy for ischemic cardiovascular diseases: some lessons learned from the first clinical trials. Trends Cardiovasc Med 14:295–300

    Article  Google Scholar 

  • Zisch AH (2003) Cell-demanded release of VEGF from synthetic, biointeractive cell-ingrowth matrices for vascularized tissue growth. FASEB J 17:2260–2262

    Article  Google Scholar 

  • Zisch AH, Lutolf MP, Hubbell JA (2003) Biopolymeric delivery matrices for angiogenic growth factors. Cardiovasc Pathol 12:295–310

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dr. Lily Xiang Laboratory, Genomic Institute of Novartis Research Foundation, San Diego, CA, USA

    Veronica Sacchi

  2. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria

    Rainer Mittermayr

  3. Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland

    Martin Ehrbar

Authors
  1. Veronica Sacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rainer Mittermayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Ehrbar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rainer Mittermayr .

Editor information

Editors and Affiliations

  1. Austrian Cluster for Tissue Engineering, Vienna, Austria

    Wolfgang Holnthoner

  2. Department of Biomedicine, University Hospital Basel, Basel, Switzerland

    Andrea Banfi

  3. Institute for Pathology, Johannes Gutenberg University, Mainz, Germany

    James Kirkpatrick

  4. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, Wien, Austria

    Heinz Redl

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Sacchi, V., Mittermayr, R., Ehrbar, M. (2021). Therapeutic Angiogenesis in Regenerative Medicine. In: Holnthoner, W., Banfi, A., Kirkpatrick, J., Redl, H. (eds) Vascularization for Tissue Engineering and Regenerative Medicine. Reference Series in Biomedical Engineering(). Springer, Cham. https://doi.org/10.1007/978-3-319-54586-8_6

Download citation

Publish with us

Policies and ethics

Search

Navigation