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Titolo:
Sustained and therapeutic delivery of factor IX in nude haemophilia B miceby encapsulated C2C12 myoblasts: concurrent tumourigenesis
Autore:
Hortelano, G; Wang, L; Xu, N; Ofosu, FA;
Indirizzi:
McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8N 3Z5, Canada McMaster Univ Hamilton ON Canada L8N 3Z5 ed, Hamilton, ON L8N 3Z5, Canada McMaster Univ, Canadian Blood Serv, Hamilton, ON L8N 3Z5, Canada McMaster Univ Hamilton ON Canada L8N 3Z5 rv, Hamilton, ON L8N 3Z5, Canada Salk Inst, Genet Lab, La Jolla, CA USA Salk Inst La Jolla CA USASalk Inst, Genet Lab, La Jolla, CA USA
Titolo Testata:
HAEMOPHILIA
fascicolo: 2, volume: 7, anno: 2001,
pagine: 207 - 214
SICI:
1351-8216(200103)7:2<207:SATDOF>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEFICIENT MOUSE MODEL; HEMOPHILIA-B; GENE-THERAPY; IN-VIVO; RETROVIRAL VECTOR; CLINICAL-TRIALS; EXPRESSION; CELLS; PERSISTENT; CANINE;
Keywords:
C2C12 myoblast; factor IX; gene therapy; haemophilia B; microcapsules;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Hortelano, G McMaster Univ, Dept Pathol & Mol Med, HSC Room 3N26, Hamilton, ON L8N 3Z5,Canada McMaster Univ HSC Room 3N26 Hamilton ON Canada L8N 3Z5 Canada
Citazione:
G. Hortelano et al., "Sustained and therapeutic delivery of factor IX in nude haemophilia B miceby encapsulated C2C12 myoblasts: concurrent tumourigenesis", HAEMOPHILIA, 7(2), 2001, pp. 207-214

Abstract

This study reports the generation of an immunodeficient murine model for haemophilia B, obtained by breeding factor IX-deficient mice with an immunodeficient mouse strain, and use of this mouse model to evaluate the long-term efficacy and safety of a gene therapy strategy for treating haemophilia B. Nude haemophilic mice were implanted with biocompatible microcapsules enclosing recombinant myoblasts secreting human factor IX. The activated partial thromboplastin time (APTT) of plasma of mice thus treated was invariablyshortened 3 weeks after microcapsule implantation, and remained shortened for at least 77 days. Shortening of the APTT of the haemophilia mice coincided with the appearance of human factor IX in mice plasmas (up to 600 ng mL(-1) on day 77), and normalization of the tail-bleeding time. Thus, the microencapsulated myoblasts reversed the clinical phenotype of haemophilia B. In contrast, plasmas of immunocompetent haemophilic mice similarly implanted with microcapsules only showed a transient shortening of APTT, and coincident transient delivery of human factor IX antigen. Rapid disappearance of human factor IX from plasmas of immunocompetent mice also coincided with production of antibodies to the human transgene. Significantly, 86% of the nude haemophilia mice developed tumours of myoblast origin. Thus, while this study revealed the feasibility of this gene therapy approach to treat severe haemophilia B, it also highlights the importance of using safer cell lines to prevent tumour development.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 00:25:14