TY - JOUR
T1 - Methylcellulose as a scaffold for the establishment of liver-organoids for the potential of treating acute live failure
AU - Chandrashekran, Anil
AU - Mitry, Ragai
AU - Premachandra, Tharindu
AU - Starling, Chris
AU - Lehec, Sharon
AU - Iansante, Valeria
AU - Fitzpatrick, Emer Catherine
AU - Fillipi, Celine
AU - Deheragoda, Maesha
AU - Hay, David
AU - Dhawan, Anil
PY - 2018
Y1 - 2018
N2 - Much progress has been made in understanding the development of human organs through advanced cellular and molecular techniques. Acute liver failure (ALF) in children is a life-threatening condition that relies on liver or hepatocyte transplantation. The translation of novel regenerative medicine strategies for the treatment of ALF is however somewhat limited. Here, we show that in vitro liver-organoids derived from human umbilical cord derived mesenchymal stem cells and human cadaveric donor-derived hepatocytes, cultured in a clinically appropriate manner, exhibit liver function. We obtained organoids that varied in size and morphology which produced albumin, and detoxified ammonium chloride into urea. Immunohistochemistry of these organoids revealed hepatocyte specific, non-parenchymal markers and histological organisation. Our in vitro findings indicate that these organoids may be a useful bridge in ALF while awaiting liver recovery or transplant. The organoid culture system we have established here is also well suited to drug screening and disease modeling.
AB - Much progress has been made in understanding the development of human organs through advanced cellular and molecular techniques. Acute liver failure (ALF) in children is a life-threatening condition that relies on liver or hepatocyte transplantation. The translation of novel regenerative medicine strategies for the treatment of ALF is however somewhat limited. Here, we show that in vitro liver-organoids derived from human umbilical cord derived mesenchymal stem cells and human cadaveric donor-derived hepatocytes, cultured in a clinically appropriate manner, exhibit liver function. We obtained organoids that varied in size and morphology which produced albumin, and detoxified ammonium chloride into urea. Immunohistochemistry of these organoids revealed hepatocyte specific, non-parenchymal markers and histological organisation. Our in vitro findings indicate that these organoids may be a useful bridge in ALF while awaiting liver recovery or transplant. The organoid culture system we have established here is also well suited to drug screening and disease modeling.
U2 - 10.18609/cgti.2018.111
DO - 10.18609/cgti.2018.111
M3 - Article
SP - 1087
EP - 1104
JO - Cell and Gene Therapy Insights
JF - Cell and Gene Therapy Insights
ER -
