Retroviral Modification of Mesenchymal Stem Cells for Gene Therapy of Hemophilia View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2008

AUTHORS

Joseph M. Le Doux , Christopher B. Doering

ABSTRACT

Mesenchymal stem cells (MSCs) are a promising target for the delivery of secreted proteins due to their ease of isolation, expansion, and genetic modification. The bleeding disorder hemophilia A results from the deficiency of a secreted blood clotting factor termed factor VIII (fVIII). Hemophilia A could be cured by gene-transfer-based procedures targeting virtually any cell type, including MSCs. Here, we describe methods for retroviral modification of MSCs incorporating a high-expression porcine (HEP)-fVIII transgene and a murine model of hemophilia A. MSCs were isolated from bone marrow of hemophilia A mice, expanded, and transduced ex vivo. Genetically modified MSCs secreted high levels of HEP-fVIII into the conditioned medium. HEP-fVIII was purified from the conditioned medium and demonstrated to have a specific activity, relative electrophoretic mobility, and proteolytic activation pattern similar to HEP-fVIII produced by other commercial cell lines. Collectively, these data support the concept that MSCs can be utilized as a cellular vehicle for successful gene-transfer-based therapy of hemophilia A and other disorders resulting from the deficiency of a secreted protein. More... »

PAGES

203-12

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-1-59745-237-3_12

DOI

http://dx.doi.org/10.1007/978-1-59745-237-3_12

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019943799

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18679625


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