Human decidua-derived mesenchymal stromal cells differentiate into hepatic-like cells and form functional three-dimensional structures.
OBJECTIVE
Previously, we have shown that human decidua-derived mesenchymal stromal cells (DMSC) are mesenchymal stromal cells (MSC) with a clonal differentiation capacity for the three embryonic layers. The endodermal capacity of DMSC was revealed by differentiation into pulmonary cells. In this study, we examined the hepatic differentiation of DMSC.


METHODS
DMSC were cultured in hepatic differentiation media or co-cultured with murine liver homogenate and analyzed with phenotypic, molecular and functional tests.


CONCLUSIONS
DMSC in hepatic differentiation media changed their fibroblast morphology to a hepatocyte-like morphology and later formed a 3-dimensional (3-D) structure or hepatosphere. Moreover, the hepatocyte-like cells and the hepatospheres expressed liver-specific markers such as synthesis of albumin (ALB), hepatocyte growth factor receptor (HGFR), α-fetoprotein (AFP) and cytokeratin-18 (CK-18), and exhibited hepatic functions including glycogen storage capacity and indocyanine green (ICG) uptake/secretion. Human DMSC co-cultured with murine liver tissue homogenate in a non-contact in vitro system showed hepatic differentiation, as evidenced by expression of AFP and ALB genes. The switch in the expression of these two genes resembled liver development. Indeed, the decrease in AFP and increase in ALB expression throughout the co-culture were consistent with the expression pattern observed during normal liver organogenesis in the embryo. Interestingly, AFP and ALB expression was significantly higher when DMSC were co-cultured with injured liver tissue, indicating that DMSC respond differently under normal and pathologic micro-environmental conditions. In conclusion, DMSC-derived hepatospheres and DMSC co-cultured with liver homogenate could be suitable in vitro models for toxicologic, developmental and pre-clinical hepatic regeneration studies.
Madrid Cord Blood Bank, Hospital Universitario 12 de Octubre, Madrid, Spain.
Rafael
R
Bornstein
Maria I
MI
Macias
Paz
P
de la Torre
Jesus
J
Grande
Ana I
AI
Flores
D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D018920:Coculture Techniques; D003656:Decidua / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism; D008099:Liver / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D060888:Real-Time Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism
D000418:Albumins; D006003:Glycogen; D007208:Indocyanine Green