← Back to Search
Systems For Therapeutic Angiogenesis In Tissue Engineering
S. Soker, M. Machado, A. Atala
Published 2000 · Medicine, Biology
Download PDFAnalyze on Scholarcy
Abstract The goals in tissue engineering include the replacement of damaged, injured, or missing body tissues with biologically compatible substitutes. To overcome initial tissue-mass loss, improved vascularization of the regenerated tissue is essential. Two pathways of tissue neovascularization are known: vasculogenesis, the in situ assembly of capillaries from undifferentiated endothelial cells (EC), and angiogenesis, the sprouting of capillaries from preexisting blood vessels. Recent advances in our understanding of the process of blood-vessel growth have provided significant tools for the neovascularization of bioengineered tissues. Several growth factors serve as stimuli for EC proliferation and migration as well as the formation of new blood vessels. They convey their effects via specific receptors expressed on the surface of EC. Vascular epithelial growth factor (VEGF) is a major regulator of neovascularization. VEGF plays a major role in the early development of blood-cell progenitors. Basic fibroblast growth factor (bFGF) was identified as the first angiogenic factor. It is a potent inducer of EC proliferation and blood-vessel growth in vitro and in vivo. VEGF and bFGF have been injected into undervascularized ischemic tissues, resulting in new blood-vessel formation and tissue perfusion. Gene-therapy approaches using VEGF cDNA injection into ischemic tissues have augmented the formation of collateral vessels. Angiogenic factors such as VEGF and bFGF have also been incorporated into bioengineered tissues and have facilitated blood-vessel growth. Other approaches such as prevascularization of the matrix prior to cell seeding and incorporation of EC into the bioengineered tissues have produced encouraging results. This article reviews the process of blood-vessel growth and tissue vascularization, placing emphasis on strategies that can be employed for efficient vascularization of engineered tissues in vitro and in vivo.
This paper references
Angiogenesis and inflammation
Sara Abdulla (1999)
Mechanisms of angiogenesis
W. Risau (1997)
Growing new organs.
D. Mooney (1999)
Development of Technologies Aiding Large‐Tissue Engineering
P. Eiselt (1998)
Induction of neoangiogenesis in ischemic myocardium by human growth factors: first clinical results of a new treatment of coronary heart disease.
B. Schumacher (1998)
Human hepatocyte isolation and transplantation into an athymic rat, using prevascularized cell polymer constructs.
M. Fontaine (1995)
Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms.
K. Houck (1992)
Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation
T. Sato (1995)
Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation.
G. Breier (1992)
CELL TRANSPLANTATION OF GENETICALLY ALTERED CELLS ON BIODEGRADABLE POLYMER SCAFFOLDS IN SYNGENEIC RATS
J. Gilbert (1993)
Vascular endo- thelial growth factor induced by hypoxia may mediate hyp- oxia-initiated angiogenesis
D Shweiki (1992)
Fighting cancer by attacking its blood supply.
J. Folkman (1996)
Site-specific therapeutic angiogenesis after systemic administration of vascular endothelial growth factor.
C. Bauters (1995)
Endostatin: An Endogenous Inhibitor of Angiogenesis and Tumor Growth
M. O'reilly (1997)
Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor
A. Yayon (1991)
Platelet-derived growth factor.
R. Ross (1989)
Basic fibroblast growth factor is an extracellular matrix component required for supporting the proliferation of vascular endothelial cells and the differentiation of PC12 cells
S. Rogelj (1989)
Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family.
M. Shibuya (1990)
Accelerated restitution of endothelial integrity and endothelium-dependent function after phVEGF165 gene transfer.
T. Asahara (1996)
Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes.
S. Frank (1995)
The role of angiogenesis in tumor growth.
J. Folkman (1992)
Blood vessel maturation: vascular development comes of age.
D. Darland (1999)
Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
F. Shalaby (1995)
Distribution of vascular permeability factor (vascular endothelial growth factor) in tumors: concentration in tumor blood vessels
H. Dvorak (1991)
Autocrine angiogenic vascular prosthesis with bone marrow transplantation
Y. Noishiki (1996)
Plasma binding proteins for platelet-derived growth factor that inhibit its binding to cell-surface receptors.
E. Raines (1984)
Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb
J. Isner (1996)
Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis.
D. Shweiki (1993)
The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors
S. Takagi (1991)
The fmslike tyrosine kinase , a receptor for vascular endothelial growth factor
C DeVries (1992)
VEGFs, receptors and angiogenesis.
T. Veikkola (1999)
Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a lewis lung carcinoma
M. O'reilly (1994)
Structural evidence that endothelial cell growth factor beta is the precursor of both endothelial cell growth factor alpha and acidic fibroblast growth factor.
W. Burgess (1986)
Cartilage reconstruction in head and neck surgery: comparison of resorbable polymer scaffolds for tissue engineering of human septal cartilage.
N. Rotter (1998)
Vasculogenesis, Angiogenesis, and Growth Factors: Ephrins Enter the Fray at the Border
G. Yancopoulos (1998)
Biological roles of fibroblast growth factor-2.
A. Bikfalvi (1997)
Vascular permeability factor, an endothelial cell mitogen related to PDGF.
P. J. Keck (1989)
Engineering the tissue which encapsulates subcutaneous implants. III. Effective tissue response times.
A. Sharkawy (1998)
Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant basic fibroblast growth factor in a rabbit model of acute lower limb ischemia: dose-response effect of basic fibroblast growth factor.
R. Baffour (1992)
VEGF/VPF: The angiogenesis factor found?
M. Klagsbrun (1993)
Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis.
J. Folkman (1995)
The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.
C. de Vries (1992)
A model of angiogenesis in the mouse cornea.
B. Kenyon (1996)
of genetically altered cells on biodegradable polymer sca olds in syngeneic rats
JC Gilbert (1993)
Inhibition of Vascular Endothelial Growth Factor (VEGF)-induced Endothelial Cell Proliferation by a Peptide Corresponding to the Exon 7-Encoded Domain of VEGF165 *
S. Soker (1997)
Characterization of Novel Vascular Endothelial Growth Factor (VEGF) Receptors on Tumor Cells That Bind VEGF via Its Exon 7-encoded Domain (*)
S. Soker (1996)
Therapeutic angiogenesis for heart failure
J. Isner (1999)
Clinical Applications of Research on Angiogenesis
J. Folkman (1995)
Molecular mechanisms of vasculogenesis and embryonic angiogenesis
I. Flamme (1997)
Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis
D. Shweiki (1992)
VEGF gene delivery to muscle: potential role for vasculogenesis in adults.
M. Springer (1998)
Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity.
M. Pepper (1997)
Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor.
A. Yanagisawa-Miwa (1992)
Increased Vascularization and Heterogeneity of Vascular Structures Occurring in Polyglycolide Matrices Containing Aortic Endothelial Cells Implanted in the Rat
W. Holder (1997)
Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium
G. Fong (1995)
The Carboxyl-terminal Domain(111165) of Vascular Endothelial Growth Factor Is Critical for Its Mitogenic Potency (*)
B. Keyt (1996)
Signaling Vascular Morphogenesis and Maintenance
D. Hanahan (1997)
A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices.
R. Vernon (1999)
Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188
P. Carmeliet (1999)
Vascular endothelial growth factor: gene therapy and therapeutic angiogenesis.
J. Isner (1998)
Dynamics of neovascularization in normal tissue.
D. F. Zawicki (1981)
Angiogenesis and Vasculogenesis in Treatment of Cardiovascular Disease
A. Rivard (1998)
Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization
Tomono Takahashi (1999)
Reconstruction of human corpus cavernosum smooth muscle and endothelial cells in vivo
HJ Park (1999)
Hypoxia-inducible Protein Binding to Vascular Endothelial Growth Factor mRNA and Its Modulation by the von Hippel-Lindau Protein*
A. Levy (1996)
The FGF family of growth factors and oncogenes.
C. Basilico (1992)
Molecular cloning of murine
H Finnerty (1993)
VEGF contributes to postnatal neovascularization by mobilizing bone marrow‐derived endothelial progenitor cells
T. Asahara (1999)
The Regulation of Blood Vessel Growth by Vascular Endothelial Growth Factor
N. Ferrara (1995)
Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor.
J. Abraham (1986)
The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.
J. Park (1993)
Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor.
B. Terman (1992)
Angiogenesis Inhibitors Generated by Tumors
J. Folkman (1995)
Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis.
K. Plate (1993)
Future perspectives in reconstructive surgery using tissue engineering.
A. Atala (1999)
Biomaterials in tissue
JA Hubbel (1995)
Isolation of Putative Progenitor Endothelial Cells for Angiogenesis
T. Asahara (1997)
Hypoxic Induction of Endothelial Cell Growth Factors in Retinal Cells: Identification and Characterization of Vascular Endothelial Growth Factor (VEGF) as the Mitogen
D. Shima (1995)
Angiogenesis and angiogenesis inhibition: an overview.
J. Folkman (1997)
A dual receptor system is required for basic fibroblast growth factor activity
M. Klagsbrun (1991)
Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.
H. Dvorak (1995)
M. Höckel (1993)
W Risau (1995)
Quantitative angiogenesis assays: Progress and problems
R. Jain (1997)
Blood Vessel Formation: What Is Its Molecular Basis?
J. Folkman (1996)
Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis
D. Hanahan (1996)
Post-transcriptional Regulation of Vascular Endothelial Growth Factor by Hypoxia (*)
A. Levy (1996)
Neuropilin-1 Is Expressed by Endothelial and Tumor Cells as an Isoform-Specific Receptor for Vascular Endothelial Growth Factor
S. Soker (1998)
Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.
S. Takeshita (1994)
Biomaterials in Tissue Engineering
J. Hubbell (1995)
The angiopoietins: Yin and Yang in angiogenesis.
S. Davis (1999)
The biology of vascular endothelial growth factor.
N. Ferrara (1997)
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
N. Ferrara (1996)
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
P. Carmeliet (1996)
Prevascularization of porous biodegradable polymers
A. Mikos (1993)
Quantitation of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane.
M. Nguyen (1994)
The cellular and molecular mechanisms of diabetic complications.
G. King (1996)
Molecular cloning of murine FLT and FLT4.
H. Finnerty (1993)
Tissue engineering : emerging concepts
M Machluf (1998)
Gene transfer of naked DNA encoding for three isoforms of vascular endothelial growth factor stimulates collateral development in vivo.
S. Takeshita (1996)
Angiogenesis and in ̄ammation. In: Gallin JI,Goldstein IM, SnydermanR (eds) In ̄ammation: basic principles and clinical correlates
J Folkman (1992)
Morphogenesis of the First Blood Vessels
C. Drake (1998)
This paper is referenced by
Reconstruction of three-dimensional neourethra using lingual keratinocytes and corporal smooth muscle cells seeded acellular corporal spongiosum.
C. Feng (2011)
Effect of platelet-rich plasma and latissimus dorsi muscle flap on osteogenesis and vascularization of tissue-engineered bone in dogs.
N. Li (2009)
A pilot study investigating a novel subcutaneously implanted pre-cellularised scaffold for tissue engineering of intestinal mucosa.
D. A. J. Lloyd (2006)
Future of Fat as Raw Material for Tissue Regeneration
Daniel A De Ugarte (2003)
Design of nano- and microfiber combined scaffolds by electrospinning of collagen onto starch-based fiber meshes: a man-made equivalent of natural extracellular matrix.
K. Tuzlakoglu (2011)
Mesoporous Bioactive Glass-Based Controlled Release Systems
J. Hum (2016)
A Review on Some Natural Biopolymers and Their Applications in Angiogenesis and Tissue Engineering
H. Nosrati (2018)
1,25-Dihydroxyvitamin D3 stimulates bone neovascularization by enhancing the interactions of osteoblasts-like cells and endothelial cells.
T. Li (2008)
Stem cell bioprocessing: fundamentals and principles
Mark R Placzek (2008)
The impact of proteinase-induced matrix degradation on the release of VEGF from heparinized collagen matrices.
C. Yao (2006)
Angiogenic gene modification of skeletal muscle cells to compensate for ageing‐induced decline in bioengineered functional muscle tissue
Dawn M. Delo (2008)
Reciprocal induction of human dermal microvascular endothelial cells and human mesenchymal stem cells: time‐dependent profile in a co‐culture system
M. Laranjeira (2012)
Calcium phosphate bone cements, functionalized with VEGF: release kinetics and biological activity.
A. Lode (2007)
Marine Phytochemical Compounds and Their Cosmeceutical Applications
S. Kim (2016)
Modulation of angiogenic potential of collagen matrices by covalent incorporation of heparin and loading with vascular endothelial growth factor.
G. C. Steffens (2004)
Composition options for tissue-engineered bone.
J. M. Orban (2002)
A novel tissue prefabrication model in rabbit using polyacrylamide cryogel scaffolds
N. Ozturk (2009)
Role of hyaluronan in angiogenesis and its utility to angiogenic tissue engineering
Erin L Pardue (2008)
The effect of cross-linking of collagen matrices on their angiogenic capability.
C. Yao (2008)
Titanium Alloys in Orthopaedics
W. Wang (2013)
The effect of hyaluronic acid hydrogels on dental pulp stem cells behavior.
E. Ahmadian (2019)
Tissue Engineering a Complete Vaginal Replacement From a Small Biopsy of Autologous Tissue
Roger E. De Philippo (2008)
Microvascular transplantation after acute myocardial infarction.
B. Shepherd (2007)
Controlled release of fibrin matrix-conjugated platelet derived growth factor improves ischemic tissue regeneration by functional angiogenesis.
R. Mittermayr (2016)
Engineering Vascularized Adipose Tissue
F. Verseijden (2011)
Silicon-dioxide-polyvinylpyrrolidone as a wound dressing for skin defects in a murine model.
F. Öri (2017)
Mathematical modelling of tissue-engineered angiogenesis.
G. Lemon (2009)
Tissue Engineering through Additive Manufacturing
Roger M. Ilagan (2016)
Localized angiogenesis induced by human vascular endothelial growth factor-activated PLGA sponge.
A. E. Elçin (2006)
Vascularization of Biomaterials for Bone Tissue Engineering: Current Approaches and Major Challenges
E. Jabbarzadeh (2012)
Tethering peptides onto biomimetic and injectable nanofiber microspheres to direct cellular response.
J. V. John (2019)
Bioactive polymer scaffold for fabrication of vascularized engineering tissue
Irza Sukmana (2012)See more