Arginine-glycine-aspartic acid-polyethylene glycol-polyamidoamine dendrimer conjugate improves liver-cell aggregation and function in 3-D spheroid culture.
The polyamidoamine (PAMAM) dendrimer, a type of macromolecule material, has been used in spheroidal cell culture and drug delivery in recent years. However, PAMAM is not involved in the study of hepatic cell-spheroid culture or its biological activity, particularly in detoxification function. Here, we constructed a PAMAM-dendrimer conjugate decorated by an integrin ligand: arginine-glycine-aspartic acid (RGD) peptide. Our studies demonstrate that RGD-polyethylene glycol (PEG)-PAMAM conjugates can promote singly floating hepatic cells to aggregate together in a sphere-like growth with a weak reactive oxygen species. Moreover, RGD-PEG-PAMAM conjugates can activate the AKT-MAPK pathway in hepatic cells to promote cell proliferation and improve basic function and ammonia metabolism. Together, our data support the hepatocyte sphere treated by RGD-PEG-PAMAM conjugates as a potential source of hepatic cells for a biological artificial liver system.
Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital.
Zhanfei
Z
Chen
Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital.
Fen
F
Lian
Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital.
Xiaoqian
X
Wang
Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou, People's Republic of China.
Yanling
Y
Chen
Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou, People's Republic of China.
Nanhong
N
Tang
D002449:Cell Aggregation / Q000187:drug effects; D018929:Cell Culture Techniques; D050091:Dendrimers / Q000737:chemistry* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular / Q000378:metabolism*
D050091:Dendrimers; D009842:Oligopeptides; C522249:PEG-PAMAM; D017382:Reactive Oxygen Species; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D051057:Proto-Oncogene Proteins c-akt
ammonia metabolism; arginine–glycine–aspartic acid (RGD); dendrimer; liver cell; spheroid culture