Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX
| Autor: | Benjamin M. Lewis, Tushar Menon, Paul E. Monahan, Suvasini Ramaswamy, Nina Tonnu, Kevin Green, Derek Wampler, Inder M. Verma |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell Transplantation Induced Pluripotent Stem Cells Heterologous 030204 cardiovascular system & hematology medicine.disease_cause Hemophilia B General Biochemistry Genetics and Molecular Biology Cryopreservation Article Cell therapy Factor IX 03 medical and health sciences Mice 0302 clinical medicine Therapeutic index Medicine Animals Induced pluripotent stem cell Gene lcsh:QH301-705.5 Mice Knockout Mutation business.industry 3. Good health Disease Models Animal 030104 developmental biology lcsh:Biology (General) Cancer research Hepatocytes Heterografts business medicine.drug |
| Zdroj: | Cell Reports, Vol 23, Iss 5, Pp 1565-1580 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | 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. In Brief 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|