Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX.

Ramaswamy S1, Tonnu N1, Menon T2, Lewis BM1, Green KT3, Wampler D4, Monahan PE5, Verma IM6.
Source: Cell Rep
Publication Date: ()
Issue: 5: 1565-1580
Cells used in publication:
Hepatocyte, human
Species: human
Tissue Origin: liver


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