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‐Prkdcscid/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. Stem Cells Translational Medicine 2017;6:174–186
Highlights
The liver is the largest internal organ, which serves functions such as uptake, metabolism, and elimination of nutrients, xenobiotics, and endogenous toxins
Anonymous samples of healthy and hepatitis B surface antigen (HBsAg)-nucleic acid test (NAT) positive human peripheral (HNP) blood were collected from adults (18–55 years of age), and peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation
We found that the culture of such monocytes isolated from HNP blood could not last for more than 2–3 days
Summary
The liver is the largest internal organ, which serves functions such as uptake, metabolism, and elimination of nutrients, xenobiotics, and endogenous toxins. It is one of the visceral organs having the unique property of regeneration. In some clinical conditions—namely, viral hepatitis, chronic alcoholism, and autoimmune disorders—the liver is damaged irreversibly and fails to regenerate [1]. Limited availability of donors and complications associated with posttransplantation, such as the risk of graft rejection, are the major drawbacks of liver transplantation procedure Transplantation of cells such as human hepatocytes [3] isolated from cadaveric liver is a less invasive procedure than is organ transplantation. Risk of the manifestation of graft versus host disease [4] is higher, which can be avoided only by autologous transplantation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
