Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX
Summary: Hemophilia B is an ideal target for gene- and cell-based therapies because of its monogenic nature and broad therapeutic index. Here, we demonstrate the use of cell therapy as a potential long-term cure for hemophilia B in our FIX-deficient mouse model. We show that transplanted, cryopreser...
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doaj-99d1db73e32248199a75fdbc194169712020-11-25T01:16:17ZengElsevierCell Reports2211-12472018-05-0123515651580Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IXSuvasini Ramaswamy0Nina Tonnu1Tushar Menon2Benjamin M. Lewis3Kevin T. Green4Derek Wampler5Paul E. Monahan6Inder M. Verma7Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USALaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USAVertex Pharmaceuticals, 11010 Torreyana Road, San Diego, CA 92121, USALaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Cellular and Molecular Biology, San Diego State University, Campanile Drive, San Diego, CA 92182, USAThermo Fisher Scientific, Inc., 5791 Van Allen Way, Carlsbad, CA 92008, USAShire Therapeutics, 22 Grenville Street, St. Helier, Jersey JE4 8PX, UKLaboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Corresponding authorSummary: Hemophilia B is an ideal target for gene- and cell-based therapies because of its monogenic nature and broad therapeutic index. Here, we demonstrate the use of cell therapy as a potential long-term cure for hemophilia B in our FIX-deficient mouse model. We show that transplanted, cryopreserved, cadaveric human hepatocytes remain functional for more than a year and secrete FIX at therapeutic levels. Hepatocytes from different sources (companies and donors) perform comparably in curing the bleeding defect. We also generated induced pluripotent stem cells (iPSCs) from two hemophilia B patients and corrected the disease-causing mutations in them by two different approaches (mutation specific and universal). These corrected iPSCs were differentiated into hepatocyte-like cells (HLCs) and transplanted into hemophilic mice. We demonstrate these iPSC-HLCs to be viable and functional in mouse models for 9–12 months. This study aims to establish the use of cells from autologous and heterologous sources to treat hemophilia B. : Ramaswamy et al. show that hepatocytes transplanted into a mouse model can alleviate symptoms of hemophilia B. Induced pluripotent cells from patients with hemophilia B can be gene-corrected and converted to hepatocyte-like cells for cell therapy. This provides evidence for potential treatment of monogenic diseases of the liver using cell therapy. Keywords: cell therapy, hemophilia, liver, iPSc derived hepatocyte-like cells, autologous cell therapy, heterologous cell therapy, monogenic liver diseaseshttp://www.sciencedirect.com/science/article/pii/S2211124718304972 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Suvasini Ramaswamy Nina Tonnu Tushar Menon Benjamin M. Lewis Kevin T. Green Derek Wampler Paul E. Monahan Inder M. Verma |
spellingShingle |
Suvasini Ramaswamy Nina Tonnu Tushar Menon Benjamin M. Lewis Kevin T. Green Derek Wampler Paul E. Monahan Inder M. Verma Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX Cell Reports |
author_facet |
Suvasini Ramaswamy Nina Tonnu Tushar Menon Benjamin M. Lewis Kevin T. Green Derek Wampler Paul E. Monahan Inder M. Verma |
author_sort |
Suvasini Ramaswamy |
title |
Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX |
title_short |
Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX |
title_full |
Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX |
title_fullStr |
Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX |
title_full_unstemmed |
Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX |
title_sort |
autologous and heterologous cell therapy for hemophilia b toward functional restoration of factor ix |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-05-01 |
description |
Summary: Hemophilia B is an ideal target for gene- and cell-based therapies because of its monogenic nature and broad therapeutic index. Here, we demonstrate the use of cell therapy as a potential long-term cure for hemophilia B in our FIX-deficient mouse model. We show that transplanted, cryopreserved, cadaveric human hepatocytes remain functional for more than a year and secrete FIX at therapeutic levels. Hepatocytes from different sources (companies and donors) perform comparably in curing the bleeding defect. We also generated induced pluripotent stem cells (iPSCs) from two hemophilia B patients and corrected the disease-causing mutations in them by two different approaches (mutation specific and universal). These corrected iPSCs were differentiated into hepatocyte-like cells (HLCs) and transplanted into hemophilic mice. We demonstrate these iPSC-HLCs to be viable and functional in mouse models for 9–12 months. This study aims to establish the use of cells from autologous and heterologous sources to treat hemophilia B. : Ramaswamy et al. show that hepatocytes transplanted into a mouse model can alleviate symptoms of hemophilia B. Induced pluripotent cells from patients with hemophilia B can be gene-corrected and converted to hepatocyte-like cells for cell therapy. This provides evidence for potential treatment of monogenic diseases of the liver using cell therapy. Keywords: cell therapy, hemophilia, liver, iPSc derived hepatocyte-like cells, autologous cell therapy, heterologous cell therapy, monogenic liver diseases |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718304972 |
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