There is a great interest in the development of functional hepatocytes in vitro from different types of stem cells. Multipotential mesenchymal stem cells (MSC) compose a great source for stem cell based therapy, especially, because they can be obtain from patients own tissues, sidestepping immunocompatibility and ethical issues. Among MSCs from different sources, adipose-tissue-derived mesenchymal stem cells (AT-MSCs) are very promising because of their high accessibility, proliferation ability, potentiality, and immunocompatibility.
AT-MSCs can be easily isolated from stroma vascular fraction (SVF) of adipose tissue. They represent a heterogeneous population of cells. The precise AT-MSCs’s marker profile has not been defined yet; therefore, it is still not obvious how to purify these heterogeneous fraction of cells. We postulate that one of the markers defining MSC provenance is CD105 (endoglin).
Therefore, we have sorted CD105+ fraction of AT-MSCs, expanded them, and differentiated toward hepatic-like cells. In order to check their potentiality, we have firstly differentiated sorted CD105+ AT-MSCs toward mesoderm lineages, using commercialized protocols.
We have shown here, that pure CD105+ AT-MSCs fraction revealed higher homogeneity and differentiation potential toward adipogenic, osteogenic, and chondrogenic lineages and highly inducible into the hepatogenic lineage.
Generated (by using our hepatic differentiation protocol) CD105+ AT-MSCs-derived hepatic-like cells expressed hepatocyte markers, enzymes, and functions.
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We would like to thank Dr. Satoshi Suzuki (Human and Animal Bridging Research Organization), Dr. Kazunori Aoki, Ms. Nachi Namatame, Ms. Shinobu Ueda, Dr. Akihiro Kobayashi, Ms. Ayako Inoue, Fumitaka Takeshita, and Ms. Maho Kodama (National Cancer Center Research Institute) for their valuable advice and assistance. This work was supported in part by a Grant-in-Aid for the Third-Term Comprehensive 10-year Strategy for Cancer Control; Health Science Research Grants for Research on the Human Genome and Regenerative Medicine from the Ministry of Health, Labor, and Welfare of Japan; and a Grant from Japan Health Sciences Foundation.
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