Autologous NeoHep Derived from Chronic Hepatitis B Virus Patients' Blood Monocytes by Upregulation of c-MET Signaling.
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.
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Jashdeep
J
Bhattacharjee
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Barun
B
Das
Institute of Genomics and Integrative Biology, New Delhi, India.
Disha
D
Sharma
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Preeti
P
Sahay
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Kshama
K
Jain
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Alaknanda
A
Mishra
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Srikanth
S
Iyer
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Puja
P
Nagpal
Institute of Genomics and Integrative Biology, New Delhi, India.
Vinod
V
Scaria
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Perumal
P
Nagarajan
St. Stephen's Hospital, Tis Hazari, Delhi, India.
Prakash
P
Khanduri
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Asok
A
Mukhopadhyay
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Pramod
P
Upadhyay
D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000097:blood*; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D055815:Young Adult
D015415:Biomarkers; C496592:HNF4A protein, human; D006514:Hepatitis B Surface Antigens; D051557:Hepatocyte Nuclear Factor 4; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Autologous cell therapy; Differentiation; HBsAg-NAT positive blood; Hepatectomy; Hepatocyte-like cells; c-MET signaling