Therapeutic vascularization in regenerative medicine
Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, u...
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| Vydáno v: | Stem cells translational medicine Ročník 9; číslo 4; s. 433 - 444 |
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| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Hoboken, USA
John Wiley & Sons, Inc
01.04.2020
Oxford University Press |
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| ISSN: | 2157-6564, 2157-6580, 2157-6580 |
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| Abstract | Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis.
Therapeutic angiogenesis, that is, the generation of new blood vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. A better understanding of the physiological mechanisms of vascular growth is important to exploit its therapeutic potential and for the rational design of cell, gene, and protein therapy approaches. |
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| AbstractList | Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis. Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis. Therapeutic angiogenesis, that is, the generation of new blood vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. A better understanding of the physiological mechanisms of vascular growth is important to exploit its therapeutic potential and for the rational design of cell, gene, and protein therapy approaches. Abstract Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis. Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short‐term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis. Therapeutic angiogenesis, that is, the generation of new blood vessels by delivery of specific factors, is required both for rapid vascularization of tissue‐engineered constructs and to treat ischemic conditions. A better understanding of the physiological mechanisms of vascular growth is important to exploit its therapeutic potential and for the rational design of cell, gene, and protein therapy approaches. Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue-engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short-term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis.Therapeutic angiogenesis, that is, the generation of new vessels by delivery of specific factors, is required both for rapid vascularization of tissue-engineered constructs and to treat ischemic conditions. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis. However, uncontrolled expression can lead to aberrant vascular growth and vascular tumors (angiomas). Major challenges to fully exploit VEGF potency for therapy include the need to precisely control in vivo distribution of growth factor dose and duration of expression. In fact, the therapeutic window of VEGF delivery depends on its amount in the microenvironment around each producing cell rather than on the total dose, since VEGF remains tightly bound to extracellular matrix (ECM). On the other hand, short-term expression of less than about 4 weeks leads to unstable vessels, which promptly regress following cessation of the angiogenic stimulus. Here, we will briefly overview some key aspects of the biology of VEGF and angiogenesis and discuss their therapeutic implications with a particular focus on approaches using gene therapy, genetically modified progenitors, and ECM engineering with recombinant factors. Lastly, we will present recent insights into the mechanisms that regulate vessel stabilization and the switch between normal and aberrant vascular growth after VEGF delivery, to identify novel molecular targets that may improve both safety and efficacy of therapeutic angiogenesis. |
| Audience | Academic |
| Author | Burger, Maximilian G. Gürke, Lorenz Banfi, Andrea Di Maggio, Nunzia Gianni‐Barrera, Roberto Melly, Ludovic Schaefer, Dirk J. Mujagic, Edin |
| AuthorAffiliation | 4 Vascular Surgery, Department of Surgery Basel University Hospital and University of Basel Basel Switzerland 2 Cardiac, Vascular, and Thoracic Surgery CHU UCL Namur Yvoir Belgium 1 Cell and Gene Therapy, Department of Biomedicine Basel University Hospital and University of Basel Basel Switzerland 3 Plastic and Reconstructive Surgery, Department of Surgery Basel University Hospital and University of Basel Basel Switzerland |
| AuthorAffiliation_xml | – name: 3 Plastic and Reconstructive Surgery, Department of Surgery Basel University Hospital and University of Basel Basel Switzerland – name: 2 Cardiac, Vascular, and Thoracic Surgery CHU UCL Namur Yvoir Belgium – name: 4 Vascular Surgery, Department of Surgery Basel University Hospital and University of Basel Basel Switzerland – name: 1 Cell and Gene Therapy, Department of Biomedicine Basel University Hospital and University of Basel Basel Switzerland |
| Author_xml | – sequence: 1 givenname: Roberto surname: Gianni‐Barrera fullname: Gianni‐Barrera, Roberto organization: Basel University Hospital and University of Basel – sequence: 2 givenname: Nunzia surname: Di Maggio fullname: Di Maggio, Nunzia organization: Basel University Hospital and University of Basel – sequence: 3 givenname: Ludovic surname: Melly fullname: Melly, Ludovic organization: CHU UCL Namur – sequence: 4 givenname: Maximilian G. surname: Burger fullname: Burger, Maximilian G. organization: Basel University Hospital and University of Basel – sequence: 5 givenname: Edin surname: Mujagic fullname: Mujagic, Edin organization: Basel University Hospital and University of Basel – sequence: 6 givenname: Lorenz surname: Gürke fullname: Gürke, Lorenz organization: Basel University Hospital and University of Basel – sequence: 7 givenname: Dirk J. surname: Schaefer fullname: Schaefer, Dirk J. organization: Basel University Hospital and University of Basel – sequence: 8 givenname: Andrea orcidid: 0000-0001-5737-8811 surname: Banfi fullname: Banfi, Andrea email: andrea.banfi@usb.ch organization: Basel University Hospital and University of Basel |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31922362$$D View this record in MEDLINE/PubMed |
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| Copyright | 2020 The Authors. published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. COPYRIGHT 2020 Oxford University Press 2020. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Keywords | tissue engineering genetic therapy vascular endothelial growth factor extracellular matrix neovascularization ischemia |
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| Notes | Funding information Department of Surgery of Basel University Hospital; Swiss Nanoscience Institute; European Union H2020 Program, Grant/Award Numbers: 801159, 646075; Swiss National Science Foundation, Grant/Award Number: 182357 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 Funding information Department of Surgery of Basel University Hospital; Swiss Nanoscience Institute; European Union H2020 Program, Grant/Award Numbers: 801159, 646075; Swiss National Science Foundation, Grant/Award Number: 182357 Roberto Gianni‐Barrera and Nunzia Di Maggio contributed equally to the study. |
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| Publisher | John Wiley & Sons, Inc Oxford University Press |
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| SubjectTerms | Angiogenesis Concise Review Concise Reviews Diabetes Endothelium Extracellular matrix Foot diseases Gene therapy genetic therapy Genetically modified organisms Health aspects Ischemia Morphogenesis neovascularization Pain Physiology Regenerative medicine Sarcoma Tissue engineering Tumors Vascular endothelial growth factor Vascularization Vein & artery diseases Veins & arteries |
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| Title | Therapeutic vascularization in regenerative medicine |
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