Open AccessAutologous NeoHep Derived from Chronic Hepatitis B Virus Patients’ Blood Monocytes by Upregulation of c‐MET Signaling
Author(s) -
Bhattacharjee Jashdeep,
Das Barun,
Sharma Disha,
Sahay Preeti,
Jain Kshama,
Mishra Alaknanda,
Iyer Srikanth,
Nagpal Puja,
Scaria Vinod,
Nagarajan Perumal,
Khanduri Prakash,
Mukhopadhyay Asok,
Upadhyay Pramod
Publication year - 2017
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.5966/sctm.2015-0308
Subject(s) - hbsag , biology , hepatocyte , downregulation and upregulation , albumin , immunology , hepatitis c virus , hepatitis b virus , microbiology and biotechnology , medicine , virus , in vitro , endocrinology , gene , biochemistry
In view of the escalating need for autologous cell‐based therapy for treatment of liver diseases, a novel candidate has been explored in the present study. The monocytes isolated from hepatitis B surface antigen (HBsAg) nucleic acid test (NAT)‐positive (HNP) blood were differentiated to hepatocyte‐like cells (NeoHep) in vitro by a two‐step culture procedure. The excess neutrophils present in HNP blood were removed before setting up the culture. In the first step of culture, apoptotic cells were depleted and genes involved in hypoxia were induced, which was followed by the upregulation of genes involved in the c‐MET signaling pathway in the second step. The NeoHep were void of hepatitis B virus and showed expression of albumin, connexin 32, hepatocyte nuclear factor 4‐α, and functions such as albumin secretion and cytochrome P450 enzyme‐mediated detoxification of xenobiotics. The engraftment of NeoHep derived from HBsAg‐NAT‐positive blood monocytes in partially hepatectomized NOD.CB17‐ Prkdc scid /J mice liver and the subsequent secretion of human albumin and clotting factor VII activity in serum make NeoHep a promising candidate for cell‐based therapy. S tem C ells T ranslational M edicine 2017;6:174–186