TY - JOUR
T1 - Human Amnion Epithelial Cells Produce Soluble Factors that Enhance Liver Repair by Reducing Fibrosis While Maintaining Regeneration in a Model of Chronic Liver Injury
AU - Hodge, Alexander
AU - Andrewartha, Neil
AU - Lourensz, Dinushka
AU - Strauss, Robyn
AU - Correia, Jeanne
AU - Goonetilleke, Mihiri
AU - Yeoh, George
AU - Lim, Rebecca
AU - Sievert, William
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Human amnion epithelial cells (hAECs) exert potent antifibrotic and anti-inflammatory effects when transplanted into preclinical models of tissue fibrosis. These effects are mediated in part via the secretion of soluble factors by hAECs which modulate signaling pathways and affect cell types involved in inflammation and fibrosis. Based on these reports, we hypothesized that these soluble factors may also support liver regeneration during chronic liver injury. To test this, we characterized the effect of both hAECs and hAEC-conditioned medium (CM) on liver repair in a mouse model of carbon tetrachloride (CCl4)-induced fibrosis. Liver repair was assessed by liver fibrosis, hepatocyte proliferation, and the liver progenitor cell (LPC) response. We found that the administration of hAECs or hAEC-CM reduced liver injury and fibrosis, sustained hepatocyte proliferation, and reduced LPC numbers during chronic liver injury. Additionally, we undertook in vitro studies to document both the cell-cell and paracrine-mediated effects of hAECs on LPCs by investigating the effects of co-culturing the LPCs and hAECs and hAEC-CM on LPCs. We found little change in LPCs co-cultured with hAECs. In contrast, hAEC-CM enhances LPC proliferation and differentiation. These findings suggest that paracrine factors secreted by hAECs enhance liver repair by reducing fibrosis while promoting regeneration during chronic liver injury.
AB - Human amnion epithelial cells (hAECs) exert potent antifibrotic and anti-inflammatory effects when transplanted into preclinical models of tissue fibrosis. These effects are mediated in part via the secretion of soluble factors by hAECs which modulate signaling pathways and affect cell types involved in inflammation and fibrosis. Based on these reports, we hypothesized that these soluble factors may also support liver regeneration during chronic liver injury. To test this, we characterized the effect of both hAECs and hAEC-conditioned medium (CM) on liver repair in a mouse model of carbon tetrachloride (CCl4)-induced fibrosis. Liver repair was assessed by liver fibrosis, hepatocyte proliferation, and the liver progenitor cell (LPC) response. We found that the administration of hAECs or hAEC-CM reduced liver injury and fibrosis, sustained hepatocyte proliferation, and reduced LPC numbers during chronic liver injury. Additionally, we undertook in vitro studies to document both the cell-cell and paracrine-mediated effects of hAECs on LPCs by investigating the effects of co-culturing the LPCs and hAECs and hAEC-CM on LPCs. We found little change in LPCs co-cultured with hAECs. In contrast, hAEC-CM enhances LPC proliferation and differentiation. These findings suggest that paracrine factors secreted by hAECs enhance liver repair by reducing fibrosis while promoting regeneration during chronic liver injury.
KW - amnion epithelial cells
KW - cell therapy
KW - liver fibrosis
KW - liver progenitor cells
KW - liver repair
UR - http://www.scopus.com/inward/record.url?scp=85089714339&partnerID=8YFLogxK
U2 - 10.1177/0963689720950221
DO - 10.1177/0963689720950221
M3 - Article
C2 - 32813573
AN - SCOPUS:85089714339
SN - 0963-6897
VL - 29
SP - 963689720950221
JO - Cell Transplantation
JF - Cell Transplantation
ER -