http://www.cnr.it/ontology/cnr/individuo/prodotto/ID193624
IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential. (Articolo in rivista)
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- IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential. (Articolo in rivista) (literal)
- Anno
- 2004-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1016/j.ymthe.2004.08.014 (literal)
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Francesca Ficara, Daniela B. Superchi, Raisa Jofra Hernández, Cristina Mocchetti, Nicole Carballido-Perrig, Grazia Andolfi, Sara Deola, Augusto Colombo, Claudio Bordignon, José M. Carballido, Maria Grazia Roncarolo and Alessandro Aiuti (2004)
IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential.
in Molecular therapy (Print)
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Francesca Ficara, Daniela B. Superchi, Raisa Jofra Hernández, Cristina Mocchetti, Nicole Carballido-Perrig, Grazia Andolfi, Sara Deola, Augusto Colombo, Claudio Bordignon, José M. Carballido, Maria Grazia Roncarolo and Alessandro Aiuti (literal)
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- 1 San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy
2 Novartis Research Institute, Vienna, Austria
3 Institute for Obstetrics and Gynecology \"L. Mangiagalli,\" ICP, Milan, Italy
4 Università Vita-Salute San Raffaele, Milan, Italy (literal)
- Titolo
- IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential. (literal)
- Abstract
- To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources. The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34+ cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. Under these optimized conditions transduced CD34+ cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34+ cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts. (literal)
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