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Titolo:
A self-immunomodulating myoblast cell line for erythropoietin delivery
Autore:
Schneider, BL; Peduto, G; Aebischer, P;
Indirizzi:
Univ Lausanne, Sch Med, CHU Vaudois, Div Rech Chirurg, CH-1001 Lausanne, Switzerland Univ Lausanne Lausanne Switzerland CH-1001 CH-1001 Lausanne, Switzerland Univ Lausanne, Sch Med, CHU Vaudois, Gene Therapy Ctr, CH-1001 Lausanne, Switzerland Univ Lausanne Lausanne Switzerland CH-1001 CH-1001 Lausanne, Switzerland
Titolo Testata:
GENE THERAPY
fascicolo: 1, volume: 8, anno: 2001,
pagine: 58 - 66
SICI:
0969-7128(200101)8:1<58:ASMCLF>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENETICALLY MODIFIED MYOBLASTS; INTRAHEPATIC ISLET ALLOGRAFTS; LONG-TERM SURVIVAL; IMMUNE-RESPONSES; MONOCLONAL-ANTIBODIES; HUMANIZED ANTI-CD154; CARDIAC ALLOGRAFTS; DENDRITIC CELLS; MICE; CTLA4;
Keywords:
CTLA4lg; anti-CD154 antibodies; immunomodulation; C2C12; erythropoietin; myoblast;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Aebischer, P Univ Lausanne, Sch Med, CHU Vaudois, Div Rech Chirurg, Pavillon 4, CH-1001Lausanne, Switzerland Univ Lausanne Pavillon 4 Lausanne Switzerland CH-1001 erland
Citazione:
B.L. Schneider et al., "A self-immunomodulating myoblast cell line for erythropoietin delivery", GENE THER, 8(1), 2001, pp. 58-66

Abstract

The transplantation of genetically engineered cells faces limitations associated with host immunity. Allogeneic cells are typically rejected in response to inherent histo-incompatibility. Even autologous cells can induce an immune response toward antigenic molecules expressed following transfer of foreign genes. The goal of the present study was to investigate the abilityof immunomodulating molecules coexpressed with biotherapeutic factors to overcome these limitations both in syngeneic and allogeneic cell transplantation. The C2C12 mouse myoblast cell line was engineered to express CTLA4lg,a soluble factor blocking T cell costimulation, in conjunction with erythropoietin (Epo), a reporter biotherapeutic protein. In syngeneic C3H mice, myoblasts expressing only mouse Epo were mostly rejected within 2 weeks, as indicated by the transient increase in host hematocrit. In allogeneic recipients, the same cells induced only a 1-week increase in the hematocrit reflecting an acute rejection process. CTLA4lg expression significantly extended the survival of mouse Epo-secreting myoblasts in approximately half of syngeneic hosts, whereas if led only to a 1-week improvement effect in allogeneic recipients. When combined with a transient anti-CD154 treatment, CTLA4lg expression prevented Epo-secreting C2C12 myoblasts from being rejected in allogeneic DBA/2J recipients for at least 1 month. In contrast, the same anti-CD154 treatment alone induced only a I week improvement. These resultsdemonstrate that CTLA4lg co-expression associated with a transient anti-CD154 treatment can prolong the delivery of recombinant proteins via transferof ex vivo modified cells in allogeneic recipients.

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Documento generato il 27/09/20 alle ore 07:14:50