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Wang H.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Zhao T.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Xu F.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Li Y.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | And 7 more authors.
Cytotherapy | Year: 2014

Background aims: The protocols for differentiation of hepatocyte-like cells (HLCs) from mesenchymal stromal cells (MSCs) have been well established. Previous data have shown that MSCs and their derived HLCs were able to engraft injured liver and alleviate injuries induced by carbon tetrachloride. The goal of the current study was to determine the differences of MSCs and their derived HLCs in terms of therapeutic functions in liver diseases. Methods: After hepatic differentiation of umbilical cord-derived MSCs in vitro, we detected both MSC and HLC expressions of adhesion molecules and chemokine receptor CXCR4 by flow cytometry; immunosuppressive potential and hepatocyte growth factor expression were determined by means of enzyme-linked immunosorbent assay. We compared the therapeutic effect for fulminant hepatic failure in a mouse model. Results: MSC-derived-HLCs expressed lower levels of hepatocyte growth factor, accompanied by impaired immunosuppression in comparison with MSCs. Furthermore, undifferentiated MSCs showed rescuing potentials superior to those in HLCs for the treatment of fulminant hepatic failure. Conclusions: After differentiation, HLCs lost several major properties in comparison with undifferentiated MSCs, which are beneficial for their application in liver diseases. Undifferentiated MSCs may be more appropriate than are HLCs for the treatment of liver diseases. © 2014 International Society for Cellular Therapy. Source


Liu G.-Y.,Tianjin University | Liu G.-Y.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Xu Y.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Li Y.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | And 3 more authors.
Cytotherapy | Year: 2013

Background aims: Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) possess broad and potent immunomodulatory activities and have shown great potential in anti-inflammatory therapies. However, a biomarker that can be used to assess quickly and efficiently the immunomodulatory function of UC-MSCs has not been identified. Several studies have revealed that galectin-3 (Gal-3), a member of the human galectin family, is involved in the immunosuppressive function of MSCs. Methods: Gal-3 gene expression in UC-MSCs was analyzed using quantitative reverse transcriptase polymerase chain reaction and Western blotting. Blocking of Gal-3 expression in UC-MSCs with small interfering RNA was employed to analyze whether the immunosuppressive function of UC-MSCs was affected. Results: We found that UC-MSCs expressed Gal-3 both on the cell surface and in secreted form, and the expression levels of Gal-3 did not show significant variation after cell passaging. We further showed that Gal-3 expression correlated with the immunosuppressive function of UC-MSCs because knock-down of Gal-3 expression with small interfering RNA significantly abrogated the inhibitory effects of UC-MSCs on mitogen-stimulated and alloantigen-stimulated proliferation of human peripheral blood mononuclear cells; meanwhile, the inhibitory effect of UC-MSCs was reversed by adding back recombinant Gal-3 to the co-culture systems. The inhibitory activities of human UC-MSCs were not reduced even when they were separated from human peripheral blood mononuclear cells in a transwell co-culture system, indicating that the soluble form of Gal-3 was the major effector. Conclusions: The Gal-3 protein secreted by UC-MSCs shows good correlation with immunosuppressive potential and may serve as a possible biomarker for the potency test of UC-MSCs. © 2013 International Society for Cellular Therapy. Source


Liu G.,Tianjin University | Liu G.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Wang L.,University of Chinese Academy of Sciences | Pang T.,University of Chinese Academy of Sciences | And 6 more authors.
Cellular and Molecular Immunology | Year: 2014

Thymic microenvironments are essential for the maturation of thymocytes, which can be anatomically compartmentalized into cortical and medullar regions. The absence of the gene encoding the transcription factor forkhead box n1 (Foxn1) causes epithelial differentiation to stall in the precursor stage, resulting in the formation of an abnormal thymus. In this study, we used human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to treat Foxn1 -/- mice, and then analyzed the maturation and distribution of thymic epithelial cells in the Foxn1 -/- thymic rudiment and the thymopoiesis of this newly developed rudiment. Our data showed a well-organized cortex-medulla architecture and an obvious improvement in the maturation of thymic epithelial cells along with the appearance of UEA-1 + MHCII hi thymic epithelial cells in the rudiment. We further demonstrated improved thymopoiesis and the enhanced export of mature T cells with increased numbers of regulatory T cells into the peripheral blood. Furthermore, we observed that MSCs can engraft into thymic tissue and express many cytokines or proteins, particularly keratinocyte growth factor (KGF) and CD248, which are essential for thymic development. Collectively, our data identified a new mechanism for MSCs, which may provide a proper microenvironment for the reconstitution and functional maturation of the thymus in Foxn1 -/- mice. Additionally, we elicited additional insights into the therapeutic efficacy of MSCs in several autoimmune diseases. © 2014 CSI and USTC. Source


Wang H.,Peking Union Medical College | Pang B.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Li Y.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Zhu D.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | And 2 more authors.
Cytotherapy | Year: 2012

Background aims. Dexamethasone (Dex) is a potent synthetic member of the glucocorticoid class of steroid drugs. Frequently, Dex has been used to enhance osteogenic, chondrogenic and adipogenic differentiation of mesenchymal stromal cells (MSC). Recently, Dex was applied to promote MSC proliferation, because of the rare frequency of MSC in bone marrow, and could protect the cells from apoptosis. The effects of Dex on MSC cytobiology behavior needs to be investigated. Methods. MSC were obtained from human umbilical cord. The surface phenotype and functional characterization of MSC cultured with different concentrations of Dex were investigated, in comparison with a control group, including MSC proliferation, apoptosis, cytokine expression and immunosuppression. Results. Different concentrations of Dex exerted diverse effects on MSC proliferation and apoptosis. Dex was also able to affect the pattern of cytokine expression of MSC. Furthermore, Dex impaired immunosuppression of MSC on peripheral blood mononuclear cells. Conclusions. A low dose of Dex favors MSC expansion in vitro, and protects against apoptosis. It is not suitable for MSC to be pre-treated with Dex when they are to be used to treat immunologic disease. However, when MSC are applied to promote angiogenesis, it is beneficial for them to be pre-treated with 10-9 mol/L Dex. © 2012 Informa Healthcare. Source


Wang L.-M.,Cell Therapy Center | Wang L.-H.,Alliancells Institute of Stem Cells and Translational Regenerative Medicine | Li M.,Cell Therapy Center | Wang Q.-Y.,Cell Therapy Center | And 4 more authors.
Chinese Journal of Tissue Engineering Research | Year: 2014

BACKGROUND: For autoimmune diseases, it is difficult to effectively solve the lack of immunological tolerance in patients by traditional treatments. Mesenchymal stem cells have the biological functions of tissue and organ regeneration and immune regulation. OBJECTIVE: To explore the effects and mechanisms of human umbilical cord-derived mesenchymal stem cells on the development of thymus in nude mice. METHODS: Human umbilical cord-derived mesenchymal stem cells were intraperitoneally injected into BABL/c nude mice at a dose of 2×106 per mouse. We analyzed the maturation and distribution of thymic epithelial cells in the thymus rudiment of nude mice and the thymopoiesis of this newly developed thymus rudiment; furthermore, we explored the therapeutic effects of human umbilical cord-derived mesenchymal stem cells. RESULTS AND CONCLUSION: Our data showed well-organized cortex-medulla structure and an obvious improvement in the maturation of thymic epithelial cells in the rudiment. We further demonstrated the improved thymopoiesis and the enhanced export of mature T cells with the T regulatory cells increase in peripheral blood. Furthermore, we found that human umbilical cord-derived mesenchymal stem cells could be engrafted in the thymus and express many cytokines, especially keratinocyte growth factor which is essential for the thymus development. These findings indicate that a new mechanism of human umbilical cord-derived mesenchymal stem cells can provide a proper microenvironment for the reconstitution and functional maturation of thymus in nude mice, and elicit another insight in terms of therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells in many autoimmune diseases. © 2014, Chinese Journal of Tissue Engineering Research. All Rights Reserved. Source

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