To Matrigel or Not to Matrigel
2008; Elsevier BV; Volume: 172; Issue: 5 Linguagem: Inglês
10.2353/ajpath.2008.071215
ISSN1525-2191
AutoresElias Polykandriotis, Andreas Arkudas, Raymund E. Horch, Ulrich Kneser, Geraldine M. Mitchell,
Tópico(s)Mesenchymal stem cell research
ResumoThis Correspondence relates to “Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis” (AmJ Pathol 2007, 171:2048–2057). This Correspondence relates to “Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis” (AmJ Pathol 2007, 171:2048–2057). To the Editor-in-Chief:Being in the business of axial vascularization and its application on tissue engineering and basic science for almost a decade, we still simmer with excitement every time a new publication from the Bernard O'Brien Institute of Microsurgery surfaces in the literature. In the article entitled “Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis,”1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GP Morrison WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar the authors present a well planned, well conducted study on the effects of vascular-related growth factors on adipogenesis and angiogenesis. They confirm that modulation of the assembly process is the result of a complex spatial and temporal interplay of signals and that to augment angiogenesis one has to avail oneself of several vasoactive molecules rather than one single substance. The use of Matrigel, however, prompts controversy, even when used as a factor-poor version. The authors themselves have shown it to be both adipogenic and angiogenic. Because it retains its adipogenic properties in this study, it is conceivable to believe that it retains its angiogenic properties as well. That would render it a black box for studies on angiogenesis. Using fibrin clots to perform similar studies, we have found a double benefit: use of fibrin gives rise to experiments with a clinical perspective2Polykandriotis E Tjiawi J Euler S Arkudas A Hess A Brune K Greil P Lametschwandtner A Horch RE Kneser U The venous graft as an effector of early angiogenesis in a fibrin matrix.Microvasc Res. 2007; 75: 25-33Crossref PubMed Scopus (31) Google Scholar, 3Polykandriotis E Arkudas A Horch RE Sturzl M Kneser U Autonomously vascularized cellular constructs in tissue engineering: opening a new perspective for biomedical science.J Cell Mol Med. 2007; 11: 6-20Crossref PubMed Scopus (71) Google Scholar because it is FDA approved (Matrigel, on the other hand, with the maximum thinkable likelihood, will never be granted approval), and the effects of vasoactive substances immobilized in fibrin are more readily attributable to the substances themselves rather than the matrix.4Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Sturzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (32) Google Scholar We would also like to note that the effects of vascular endothelial growth factor/basic fibroblast growth factor are not species-specific in this setting, and the use of human recombinant variants of the growth factors produces equally vivid angiogenesis in our rodent model.4Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Sturzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (32) Google ScholarAuthor's ReplyPolykandriotis and colleagues have criticized our use of the murine extracellular matrix Matrigel (derived from the Engelbreth-Holm-Swarm sarcoma), in our recent study1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GPL Morriosn WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar and imply that we should have used the FDA-approved fibrin glue as the matrix in this mouse model. Their group has used commercially available fibrin glue in in vivo studies involving the rat arterio-venous chamber model.2Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Stürzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (73) Google Scholar, 3Polykandriotis E Tjiawi J Euler S Arkudas A Hess A Brune K Greil P Lametschwandtner A Horch RE Kneser U The venous graft as an effector of early angiogenesis in a fibrin matrix.Microvasc Res. 2008; 75: 25-33Crossref PubMed Scopus (64) Google Scholar Their use of fibrin glue is not necessary to support angiogenesis in this rat model because an endogenous fibrin matrix forms between 0 to 3 days, nearly filling the chamber, and providing a proangiogenic scaffold that supports an intense angiogenic response in which 23% of the new tissue volume at 10 days is new blood vessels.4Lokmic Z Stillaert F Morrison WA Thompson EW Mitchell GM An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct.FASEB J. 2007; 21: 511-522Crossref PubMed Scopus (149) Google Scholar, 5Lokmic Z Mitchell GM The source and commencement of angiogenesis from the arterio-venous loop model.Microvasc Res. 2008; 75: 142-143Crossref PubMed Scopus (8) Google ScholarHowever, the murine model used by us (Rophael et al1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GPL Morriosn WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar) differs somewhat from the rat model—it is based on the epigastric vascular pedicle and produces little endogenous fibrin. Therefore to create a mouse tissue engineering construct that will support adipogenesis and angiogenesis, we chose growth factor-reduced (GFR) Matrigel. Matrigel is widely used in in vitro studies, has been the subject of a number of in vivo studies on adipogenesis,6Voros G Sandy JD Collen D Lijnen HR Expression of aggrecan(ases) during murine preadipocyte differentiation and adipose tissue development.Biochim Biophys Acta. 2006; 1760: 1837-1844Crossref PubMed Scopus (28) Google Scholar, 7Kelly JL Findlay MW Knight KR Penington A Thompson EW Messina A Morriosn WA Contact with existing adipose tissue is inductive for adipogenesis in Matrigel.Tissue Eng. 2006; 12: 2041-2047Crossref PubMed Scopus (70) Google Scholar and has been known to support angiogenesis since the work of Passaniti and colleagues.8Passaniti A Taylor RM Pili R Guo Y Long PV Haney JA Pauly RR Grant DS Martin GR A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor.Lab Invest. 1992; 67: 519-528PubMed Google Scholar Two recent studies have described in detail the angiogenic process within Matrigel.9Anghelina M Krishnan P Moldovan L Moldovan NI Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns onto fibrovascular bundles.Am J Pathol. 2006; 168: 529-541Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar, 10Tigges U Gore Hyer E Scarf J Stallcup WB FGF2-dependent neovascularisation of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages.Development. 2008; 135: 523-532Crossref PubMed Scopus (76) Google ScholarIt is unclear what Polykandriotis and colleagues mean by stating that Matrigel “is a black box for studies on angiogenesis.” Preliminary investigations by us in our mouse model with implanted myoblasts indicate that at 2 weeks the percent vascular volume of constructs with added natural fibrin scaffold (plasma clot harvested from mice of the same strain) is 6.79 ± 1.59% and that of GFR Matrigel is 7.60 ± 0.73% (mean ± SEM; Tilkorn D et al, unpublished observations). Thus, at least in the first 2 weeks, angiogenesis in GFR Matrigel is supported to approximately the same degree as in a biological fibrin scaffold.It must be acknowledged, as Polykandriotis and colleagues suggest, that Matrigel is unlikely to receive FDA approval and that it is not a suitable option in human tissue engineering. Fibrin glue may be suitable in human tissue engineering as a carrier of cells or growth factors if its ability to support early vascularization is improved.5Lokmic Z Mitchell GM The source and commencement of angiogenesis from the arterio-venous loop model.Microvasc Res. 2008; 75: 142-143Crossref PubMed Scopus (8) Google Scholar, 11Cassell OCS Morrison WA Messina A Penington AJ Thompson EW Stevens GW Perera JM Kleinman HK Hurley JV Romeo R Knight KR The influence of extracellular matrix on the generation of vascularised, engineered, transplantable tissue.Ann NY Acad Sci. 2001; 944: 429-442Crossref PubMed Scopus (104) Google ScholarMatrigel is considered by many, including our group, as a legitimate research tool in studies of murine adipogenesis and angiogenesis. In using any extracellular matrix, its appropriateness to support the specific tissue being grown and its compatibility with the animal model must be considered. To this end our group is working on species-specific biological alternatives to Matrigel that will support adipogenesis.12Abberton KM, Bortolotto SK, Woods A, Morrison WA, Thompson EW, Messina A: MyoGel™—A highly adipogenic novel basement membrane rich extracellular matrix hydrogel from skeletal muscle. Cell Tissue Res (in press)Google Scholar To the Editor-in-Chief:Being in the business of axial vascularization and its application on tissue engineering and basic science for almost a decade, we still simmer with excitement every time a new publication from the Bernard O'Brien Institute of Microsurgery surfaces in the literature. In the article entitled “Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis,”1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GP Morrison WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar the authors present a well planned, well conducted study on the effects of vascular-related growth factors on adipogenesis and angiogenesis. They confirm that modulation of the assembly process is the result of a complex spatial and temporal interplay of signals and that to augment angiogenesis one has to avail oneself of several vasoactive molecules rather than one single substance. The use of Matrigel, however, prompts controversy, even when used as a factor-poor version. The authors themselves have shown it to be both adipogenic and angiogenic. Because it retains its adipogenic properties in this study, it is conceivable to believe that it retains its angiogenic properties as well. That would render it a black box for studies on angiogenesis. Using fibrin clots to perform similar studies, we have found a double benefit: use of fibrin gives rise to experiments with a clinical perspective2Polykandriotis E Tjiawi J Euler S Arkudas A Hess A Brune K Greil P Lametschwandtner A Horch RE Kneser U The venous graft as an effector of early angiogenesis in a fibrin matrix.Microvasc Res. 2007; 75: 25-33Crossref PubMed Scopus (31) Google Scholar, 3Polykandriotis E Arkudas A Horch RE Sturzl M Kneser U Autonomously vascularized cellular constructs in tissue engineering: opening a new perspective for biomedical science.J Cell Mol Med. 2007; 11: 6-20Crossref PubMed Scopus (71) Google Scholar because it is FDA approved (Matrigel, on the other hand, with the maximum thinkable likelihood, will never be granted approval), and the effects of vasoactive substances immobilized in fibrin are more readily attributable to the substances themselves rather than the matrix.4Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Sturzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (32) Google Scholar We would also like to note that the effects of vascular endothelial growth factor/basic fibroblast growth factor are not species-specific in this setting, and the use of human recombinant variants of the growth factors produces equally vivid angiogenesis in our rodent model.4Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Sturzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (32) Google Scholar Being in the business of axial vascularization and its application on tissue engineering and basic science for almost a decade, we still simmer with excitement every time a new publication from the Bernard O'Brien Institute of Microsurgery surfaces in the literature. In the article entitled “Angiogenic Growth Factor Synergism in a Murine Tissue Engineering Model of Angiogenesis and Adipogenesis,”1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GP Morrison WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar the authors present a well planned, well conducted study on the effects of vascular-related growth factors on adipogenesis and angiogenesis. They confirm that modulation of the assembly process is the result of a complex spatial and temporal interplay of signals and that to augment angiogenesis one has to avail oneself of several vasoactive molecules rather than one single substance. The use of Matrigel, however, prompts controversy, even when used as a factor-poor version. The authors themselves have shown it to be both adipogenic and angiogenic. Because it retains its adipogenic properties in this study, it is conceivable to believe that it retains its angiogenic properties as well. That would render it a black box for studies on angiogenesis. Using fibrin clots to perform similar studies, we have found a double benefit: use of fibrin gives rise to experiments with a clinical perspective2Polykandriotis E Tjiawi J Euler S Arkudas A Hess A Brune K Greil P Lametschwandtner A Horch RE Kneser U The venous graft as an effector of early angiogenesis in a fibrin matrix.Microvasc Res. 2007; 75: 25-33Crossref PubMed Scopus (31) Google Scholar, 3Polykandriotis E Arkudas A Horch RE Sturzl M Kneser U Autonomously vascularized cellular constructs in tissue engineering: opening a new perspective for biomedical science.J Cell Mol Med. 2007; 11: 6-20Crossref PubMed Scopus (71) Google Scholar because it is FDA approved (Matrigel, on the other hand, with the maximum thinkable likelihood, will never be granted approval), and the effects of vasoactive substances immobilized in fibrin are more readily attributable to the substances themselves rather than the matrix.4Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Sturzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (32) Google Scholar We would also like to note that the effects of vascular endothelial growth factor/basic fibroblast growth factor are not species-specific in this setting, and the use of human recombinant variants of the growth factors produces equally vivid angiogenesis in our rodent model.4Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Sturzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (32) Google Scholar Author's ReplyPolykandriotis and colleagues have criticized our use of the murine extracellular matrix Matrigel (derived from the Engelbreth-Holm-Swarm sarcoma), in our recent study1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GPL Morriosn WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar and imply that we should have used the FDA-approved fibrin glue as the matrix in this mouse model. Their group has used commercially available fibrin glue in in vivo studies involving the rat arterio-venous chamber model.2Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Stürzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (73) Google Scholar, 3Polykandriotis E Tjiawi J Euler S Arkudas A Hess A Brune K Greil P Lametschwandtner A Horch RE Kneser U The venous graft as an effector of early angiogenesis in a fibrin matrix.Microvasc Res. 2008; 75: 25-33Crossref PubMed Scopus (64) Google Scholar Their use of fibrin glue is not necessary to support angiogenesis in this rat model because an endogenous fibrin matrix forms between 0 to 3 days, nearly filling the chamber, and providing a proangiogenic scaffold that supports an intense angiogenic response in which 23% of the new tissue volume at 10 days is new blood vessels.4Lokmic Z Stillaert F Morrison WA Thompson EW Mitchell GM An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct.FASEB J. 2007; 21: 511-522Crossref PubMed Scopus (149) Google Scholar, 5Lokmic Z Mitchell GM The source and commencement of angiogenesis from the arterio-venous loop model.Microvasc Res. 2008; 75: 142-143Crossref PubMed Scopus (8) Google ScholarHowever, the murine model used by us (Rophael et al1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GPL Morriosn WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar) differs somewhat from the rat model—it is based on the epigastric vascular pedicle and produces little endogenous fibrin. Therefore to create a mouse tissue engineering construct that will support adipogenesis and angiogenesis, we chose growth factor-reduced (GFR) Matrigel. Matrigel is widely used in in vitro studies, has been the subject of a number of in vivo studies on adipogenesis,6Voros G Sandy JD Collen D Lijnen HR Expression of aggrecan(ases) during murine preadipocyte differentiation and adipose tissue development.Biochim Biophys Acta. 2006; 1760: 1837-1844Crossref PubMed Scopus (28) Google Scholar, 7Kelly JL Findlay MW Knight KR Penington A Thompson EW Messina A Morriosn WA Contact with existing adipose tissue is inductive for adipogenesis in Matrigel.Tissue Eng. 2006; 12: 2041-2047Crossref PubMed Scopus (70) Google Scholar and has been known to support angiogenesis since the work of Passaniti and colleagues.8Passaniti A Taylor RM Pili R Guo Y Long PV Haney JA Pauly RR Grant DS Martin GR A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor.Lab Invest. 1992; 67: 519-528PubMed Google Scholar Two recent studies have described in detail the angiogenic process within Matrigel.9Anghelina M Krishnan P Moldovan L Moldovan NI Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns onto fibrovascular bundles.Am J Pathol. 2006; 168: 529-541Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar, 10Tigges U Gore Hyer E Scarf J Stallcup WB FGF2-dependent neovascularisation of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages.Development. 2008; 135: 523-532Crossref PubMed Scopus (76) Google ScholarIt is unclear what Polykandriotis and colleagues mean by stating that Matrigel “is a black box for studies on angiogenesis.” Preliminary investigations by us in our mouse model with implanted myoblasts indicate that at 2 weeks the percent vascular volume of constructs with added natural fibrin scaffold (plasma clot harvested from mice of the same strain) is 6.79 ± 1.59% and that of GFR Matrigel is 7.60 ± 0.73% (mean ± SEM; Tilkorn D et al, unpublished observations). Thus, at least in the first 2 weeks, angiogenesis in GFR Matrigel is supported to approximately the same degree as in a biological fibrin scaffold.It must be acknowledged, as Polykandriotis and colleagues suggest, that Matrigel is unlikely to receive FDA approval and that it is not a suitable option in human tissue engineering. Fibrin glue may be suitable in human tissue engineering as a carrier of cells or growth factors if its ability to support early vascularization is improved.5Lokmic Z Mitchell GM The source and commencement of angiogenesis from the arterio-venous loop model.Microvasc Res. 2008; 75: 142-143Crossref PubMed Scopus (8) Google Scholar, 11Cassell OCS Morrison WA Messina A Penington AJ Thompson EW Stevens GW Perera JM Kleinman HK Hurley JV Romeo R Knight KR The influence of extracellular matrix on the generation of vascularised, engineered, transplantable tissue.Ann NY Acad Sci. 2001; 944: 429-442Crossref PubMed Scopus (104) Google ScholarMatrigel is considered by many, including our group, as a legitimate research tool in studies of murine adipogenesis and angiogenesis. In using any extracellular matrix, its appropriateness to support the specific tissue being grown and its compatibility with the animal model must be considered. To this end our group is working on species-specific biological alternatives to Matrigel that will support adipogenesis.12Abberton KM, Bortolotto SK, Woods A, Morrison WA, Thompson EW, Messina A: MyoGel™—A highly adipogenic novel basement membrane rich extracellular matrix hydrogel from skeletal muscle. Cell Tissue Res (in press)Google Scholar Polykandriotis and colleagues have criticized our use of the murine extracellular matrix Matrigel (derived from the Engelbreth-Holm-Swarm sarcoma), in our recent study1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GPL Morriosn WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar and imply that we should have used the FDA-approved fibrin glue as the matrix in this mouse model. Their group has used commercially available fibrin glue in in vivo studies involving the rat arterio-venous chamber model.2Arkudas A Tjiawi J Bleiziffer O Grabinger L Polykandriotis E Beier JP Stürzl M Horch RE Kneser U Fibrin gel-immobilized VEGF and bFGF efficiently stimulate angiogenesis in the AV loop model.Mol Med. 2007; 13: 480-487Crossref PubMed Scopus (73) Google Scholar, 3Polykandriotis E Tjiawi J Euler S Arkudas A Hess A Brune K Greil P Lametschwandtner A Horch RE Kneser U The venous graft as an effector of early angiogenesis in a fibrin matrix.Microvasc Res. 2008; 75: 25-33Crossref PubMed Scopus (64) Google Scholar Their use of fibrin glue is not necessary to support angiogenesis in this rat model because an endogenous fibrin matrix forms between 0 to 3 days, nearly filling the chamber, and providing a proangiogenic scaffold that supports an intense angiogenic response in which 23% of the new tissue volume at 10 days is new blood vessels.4Lokmic Z Stillaert F Morrison WA Thompson EW Mitchell GM An arteriovenous loop in a protected space generates a permanent, highly vascular, tissue-engineered construct.FASEB J. 2007; 21: 511-522Crossref PubMed Scopus (149) Google Scholar, 5Lokmic Z Mitchell GM The source and commencement of angiogenesis from the arterio-venous loop model.Microvasc Res. 2008; 75: 142-143Crossref PubMed Scopus (8) Google Scholar However, the murine model used by us (Rophael et al1Rophael JA Craft RO Palmer JA Hussey AJ Thomas GPL Morriosn WA Penington AJ Mitchell GM Angiogenic growth factor synergism in a murine tissue engineering model of angiogenesis and adipogenesis.Am J Pathol. 2007; 171: 2048-2057Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar) differs somewhat from the rat model—it is based on the epigastric vascular pedicle and produces little endogenous fibrin. Therefore to create a mouse tissue engineering construct that will support adipogenesis and angiogenesis, we chose growth factor-reduced (GFR) Matrigel. Matrigel is widely used in in vitro studies, has been the subject of a number of in vivo studies on adipogenesis,6Voros G Sandy JD Collen D Lijnen HR Expression of aggrecan(ases) during murine preadipocyte differentiation and adipose tissue development.Biochim Biophys Acta. 2006; 1760: 1837-1844Crossref PubMed Scopus (28) Google Scholar, 7Kelly JL Findlay MW Knight KR Penington A Thompson EW Messina A Morriosn WA Contact with existing adipose tissue is inductive for adipogenesis in Matrigel.Tissue Eng. 2006; 12: 2041-2047Crossref PubMed Scopus (70) Google Scholar and has been known to support angiogenesis since the work of Passaniti and colleagues.8Passaniti A Taylor RM Pili R Guo Y Long PV Haney JA Pauly RR Grant DS Martin GR A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor.Lab Invest. 1992; 67: 519-528PubMed Google Scholar Two recent studies have described in detail the angiogenic process within Matrigel.9Anghelina M Krishnan P Moldovan L Moldovan NI Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns onto fibrovascular bundles.Am J Pathol. 2006; 168: 529-541Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar, 10Tigges U Gore Hyer E Scarf J Stallcup WB FGF2-dependent neovascularisation of subcutaneous Matrigel plugs is initiated by bone marrow-derived pericytes and macrophages.Development. 2008; 135: 523-532Crossref PubMed Scopus (76) Google Scholar It is unclear what Polykandriotis and colleagues mean by stating that Matrigel “is a black box for studies on angiogenesis.” Preliminary investigations by us in our mouse model with implanted myoblasts indicate that at 2 weeks the percent vascular volume of constructs with added natural fibrin scaffold (plasma clot harvested from mice of the same strain) is 6.79 ± 1.59% and that of GFR Matrigel is 7.60 ± 0.73% (mean ± SEM; Tilkorn D et al, unpublished observations). Thus, at least in the first 2 weeks, angiogenesis in GFR Matrigel is supported to approximately the same degree as in a biological fibrin scaffold. It must be acknowledged, as Polykandriotis and colleagues suggest, that Matrigel is unlikely to receive FDA approval and that it is not a suitable option in human tissue engineering. Fibrin glue may be suitable in human tissue engineering as a carrier of cells or growth factors if its ability to support early vascularization is improved.5Lokmic Z Mitchell GM The source and commencement of angiogenesis from the arterio-venous loop model.Microvasc Res. 2008; 75: 142-143Crossref PubMed Scopus (8) Google Scholar, 11Cassell OCS Morrison WA Messina A Penington AJ Thompson EW Stevens GW Perera JM Kleinman HK Hurley JV Romeo R Knight KR The influence of extracellular matrix on the generation of vascularised, engineered, transplantable tissue.Ann NY Acad Sci. 2001; 944: 429-442Crossref PubMed Scopus (104) Google Scholar Matrigel is considered by many, including our group, as a legitimate research tool in studies of murine adipogenesis and angiogenesis. In using any extracellular matrix, its appropriateness to support the specific tissue being grown and its compatibility with the animal model must be considered. To this end our group is working on species-specific biological alternatives to Matrigel that will support adipogenesis.12Abberton KM, Bortolotto SK, Woods A, Morrison WA, Thompson EW, Messina A: MyoGel™—A highly adipogenic novel basement membrane rich extracellular matrix hydrogel from skeletal muscle. Cell Tissue Res (in press)Google Scholar
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