title: Promotion of hepatic differentiation of bone marrow mesenchymal stem cells on decellularized cell-deposited extracellular matrix.
abstract: Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimicked in vivo liver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.
authors.affiliation: Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: He
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Gao
authors.forename: Yun
authors.initials: Y
authors.lastname: Ye
authors.forename: Yujie
authors.initials: Y
authors.lastname: Su
authors.forename: Qiyi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Yihong
authors.initials: Y
authors.lastname: Gong
authors.forename: Fan
authors.initials: F
authors.lastname: He
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002474:Cell-Free System; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*