TY - JOUR
T1 - Bottom-up signaling from HGF-containing surfaces promotes hepatic differentiation of mesenchymal stem cells
AU - Ghaedi, Mahboobe
AU - Tuleuova, Nazgul
AU - Zern, Mark A.
AU - Wu, Jian
AU - Revzin, Alexander
N1 - Funding Information:
We thank Prof. Jan Nolta for providing stem cells used in our experiments. We gratefully acknowledge Drs. Yuyu Duan and Ji Youn Lee for technical assistance. This work was supported by an NIH grant ( R01DK079977 ) awarded to A.R.
PY - 2011/4/8
Y1 - 2011/4/8
N2 - The capacity of stem cells to differentiate into specific cell types makes them very promising in tissue regeneration and repair. However, realizing this promise requires novel methods for guiding lineage-specific differentiation of stem cells. In this study, hepatocyte growth factor (HGF), an important morphogen in liver development, was co-printed with collagen I (Col) to create arrays of protein spots on glass. Human adipose stem cells (ASCs) were cultured on top of the HGF/Col spots for 2. weeks. The effects of surface-immobilized HGF on hepatic differentiation of ASCs were analyzed using RT-PCR, ELISA and immunocytochemistry. Stimulation of stem cells with HGF from the bottom-up caused an upregulation in synthesis of α-fetoprotein and albumin, as determined by immunocytochemistry and ELISA. RT-PCR results showed that the mRNA levels for albumin, α-fetoprotein and α1-antitrypsin were 10- to 20-fold higher in stem cells cultured on the HGF/Col arrays compared to stem cells on Col only spots. Our results show that surfaces containing HGF co-printed with ECM proteins may be used to differentiate mesenchymal stem cells such as ASCs into hepatocyte-like cells. These results underscore the utility of growth factor-containing culture surfaces for stem cell differentiation.
AB - The capacity of stem cells to differentiate into specific cell types makes them very promising in tissue regeneration and repair. However, realizing this promise requires novel methods for guiding lineage-specific differentiation of stem cells. In this study, hepatocyte growth factor (HGF), an important morphogen in liver development, was co-printed with collagen I (Col) to create arrays of protein spots on glass. Human adipose stem cells (ASCs) were cultured on top of the HGF/Col spots for 2. weeks. The effects of surface-immobilized HGF on hepatic differentiation of ASCs were analyzed using RT-PCR, ELISA and immunocytochemistry. Stimulation of stem cells with HGF from the bottom-up caused an upregulation in synthesis of α-fetoprotein and albumin, as determined by immunocytochemistry and ELISA. RT-PCR results showed that the mRNA levels for albumin, α-fetoprotein and α1-antitrypsin were 10- to 20-fold higher in stem cells cultured on the HGF/Col arrays compared to stem cells on Col only spots. Our results show that surfaces containing HGF co-printed with ECM proteins may be used to differentiate mesenchymal stem cells such as ASCs into hepatocyte-like cells. These results underscore the utility of growth factor-containing culture surfaces for stem cell differentiation.
KW - Extracellular matrix
KW - Growth factor immobilization
KW - Hepatic differentiation
KW - Mesenchymal stem cells
KW - Protein microarrays
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U2 - 10.1016/j.bbrc.2011.03.005
DO - 10.1016/j.bbrc.2011.03.005
M3 - Article
C2 - 21382341
AN - SCOPUS:79953700252
SN - 0006-291X
VL - 407
SP - 295
EP - 300
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -