Bottom-up signaling from HGF-containing surfaces promotes hepatic differentiation of mesenchymal stem cells |
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Authors: | Mahboobe Ghaedi Nazgul Tuleuova Mark A. Zern Jian Wu Alexander Revzin |
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Affiliation: | aDepartment of Biomedical Engineering, University of California, Davis, 451 Health Sciences, Dr. #2519, CA 95616, USA;bDepartment of Medicine, Transplant Research Program, University of California, Davis Medical Center, Sacramento, CA 95817, USA;cNational Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran;dNational Center for Biotechnology, Astana, Kazakhstan |
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Abstract: | 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. |
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Keywords: | Growth factor immobilization Extracellular matrix Hepatic differentiation Mesenchymal stem cells Protein microarrays |
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