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Titolo:
Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factor
Autore:
Springer, ML; Hortelano, G; Bouley, DM; Wong, J; Kraft, PE; Blau, HM;
Indirizzi:
Stanford Univ, Dept Mol Pharmacol, Sch Med, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 acol, Sch Med, Stanford, CA 94305 USA McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada McMaster Univ Hamilton ON Canada Pathol & Mol Med, Hamilton, ON, Canada Stanford Univ, Dept Comparat Med, Sch Med, Stanford, CA 94305 USA StanfordUniv Stanford CA USA 94305 Med, Sch Med, Stanford, CA 94305 USA
Titolo Testata:
JOURNAL OF GENE MEDICINE
fascicolo: 4, volume: 2, anno: 2000,
pagine: 279 - 288
SICI:
1099-498X(200007/08)2:4<279:IOABIO>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN FACTOR-IX; INTRAMUSCULAR GENE-TRANSFER; PERMEABILITY FACTOR; IN-VIVO; MYOCARDIAL ANGIOGENESIS; RECOMBINANT FIBROBLASTS; COLLATERAL DEVELOPMENT; SYSTEMIC DELIVERY; CELLS SECRETE; THERAPY;
Keywords:
VEGF; myoblasts; encapsulation; gene therapy; angiogenesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Blau, HM Stanford Univ, Dept Mol Pharmacol, Sch Med, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 Med, Stanford, CA 94305 USA
Citazione:
M.L. Springer et al., "Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factor", J GENE MED, 2(4), 2000, pp. 279-288

Abstract

Background We previously demonstrated that intramuscular implantation of primary myoblasts engineered to express vascular endothelial growth factor (VEGF) constitutively resulted in hemangioma formation and the appearance ofVEGF in the circulation. To investigate the potential for using allogeneicmyoblasts and the effects of delivery of VEGF-expressing myoblasts to nonmuscle sites, we have enclosed them in microcapsules that protect allogeneiccells from rejection, yet allow the secretion of proteins produced by the cells. Methods Encapsulated mouse primary myoblasts that constitutively expressedmurine VEGF(164), or encapsulated negative control cells, were implanted either subcutaneously or intraperitoneally into mice. Results Upon subcutaneous implantation, capsules containing VEGF-expressing myoblasts gave rise to large tissue masses at the implantation site that continued to grow and were composed primarily of endothelial and smooth muscle cells directly surrounding the capsules, and macrophages and capillaries further away from the capsules. Similarly, when injected intraperitoneally, VEGF-producing capsules caused significant localized inflammation and angiogenesis within the peritoneum, and ultimately led to fatal intraperitoneal hemorrhage. Notably, however, VEGF was not detected in the plasma of anymice. Conclusions We conclude that encapsulated primary myoblasts persist and continue to secrete VEGF subcutaneously and intraperitoneally, but that the heparin-binding isoform VEGF(164) exerts localized effects at the site of production. VEGF secreted from the capsules attracts endothelial and smooth muscle cells in a macrophage-independent manner. These results, along with our previous results, show that the mode and site of delivery of the same factor by the same engineered myoblasts can lead to markedly different outcomes. Moreover, the results confirm that constitutive delivery of high levelsof VEGF is not desirable. In contrast, regulatable expression may lead to efficacious, safe, and localized VEGF delivery by encapsulated allogeneic primary myoblasts that can serve as universal donors. Copyright (C) 2000 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 07:33:22