Autologous NeoHep Derived from Chronic Hepatitis B Virus Patients' Blood Monocytes by Upregulation of c-MET Signaling. (28th July 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Stem cells translational medicine. Volume 6:Number 1(2017)
• Page Start: 174
• Page End: 186
• Publication Date: 2016-07-28
• Subjects: HBsAg-NAT positive blood -- Differentiation -- Hepatocyte-like cells -- c-MET signaling -- Hepatectomy -- Autologous cell therapy; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2015-0308
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract: 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.