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Non-hematopoietic stem cells as factories for in vivo therapeutic protein production

Gene Therapy volume 19, pages 1–7 (2012)Cite this article

Abstract

As an alternative to recombinant protein administration, ex vivo gene-modified cells may provide a novel strategy for systemic delivery of therapeutic proteins. This approach has been used in preclinical and clinical studies of a plethora of pathological conditions, including anemia, hemophilia and cancer for the production of erythropoietin, coagulation factors, immunostimulatory cytokines, recombinant antibodies and angiogenesis inhibitors. Cell delivery vehicles may also be varied: autologous or allogeneic, precursor or terminally differentiated cells, with targeting properties or immobilized in immunoprotective devices. This field did not meet the expectation raised initially, mainly because of difficulties with obtaining therapeutic plasma levels and the short lifespan of producer cells that hampered clinical application. Different non-hematopoietic stem/progenitor cells have emerged as potential delivery vehicles, since they are easy to obtain, expand and transduce, and they exhibit prolonged lifespans (with mesenchymal stem cells probably being the most popular cell type, but not the only one). Special emphasis is placed on the different routes used to deliver these cellular vehicles and the controversies about their targeting abilities.

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Acknowledgements

This study was supported by grants from the Ministerio de Ciencia e Innovación (BIO2008-03233 and PSE-01000-2009-11), the Comunidad de Madrid (S-BIO-0236-2006) and the European Union (SUDOE-FEDER. IMMUNONET-SOE1/P1/E014) to LA-V; and from the Fondo de Investigación Sanitaria/ Instituto de Salud Carlos III (PI08/90856 and PS09/00227) and Fundación Investigación Biomédica Hospital Puerta de Hierro to LS. MC was supported by Instituto de Salud Carlos III (Contrato Rio Hortega, CM06/00055).

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LS, MC, IG-M and LA-V wrote the manuscript; LS approved the final draft of the manuscript.

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  1. Molecular Immunology Unit, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain

    L Sanz, M Compte, I Guijarro-Muñoz & L Álvarez-Vallina

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Sanz, L., Compte, M., Guijarro-Muñoz, I. et al. Non-hematopoietic stem cells as factories for in vivo therapeutic protein production. Gene Ther 19, 1–7 (2012). https://doi.org/10.1038/gt.2011.68

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