The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform

Giovanni Camussi - One of the best experts on this subject based on the ideXlab platform.

  • human Liver Stem Cell derived extraCellular vesicles prevent aristolochic acid induced kidney fibrosis
    Frontiers in Immunology, 2018
    Co-Authors: Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
    Abstract:

    With limited therapeutic intervention in preventing the progression to end stage renal disease, chronic kidney disease (CKD) remains a global healthcare burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury and interstitial fibrosis. Human Liver Stem Cell derived extraCellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA induced mouse model of CKD. NSG mice were injected with HLSC-EVs three days after administering AA on a weekly basis for four weeks. Mice injected with AA significantly lost weight over the four week period. Deterioration in kidney function was also observed. Histology was performed to evaluate tubular necrosis, interstitial fibrosis, as well as infiltration of inflammatory Cells/fibroblasts. Kidneys were also subjected to genetic array analyses to evaluate regulation of microRNAs and fibrotic genes. The effect of HLSC-EVs was also tested in vitro to assess fibrotic gene regulation in fibroblasts co-cultured with AA treated tubular epithelial Cells. Histological analyses showed that treatment with HLSC-EVs significantly reduced tubular necrosis, interstitial fibrosis, infiltration of CD45 Cells and fibroblasts which were all elevated during AA induced injury. At a molecular level, HLSC-EVs significantly inhibited the upregulation of the fibrotic genes α-Sma, Tgfb1 and Col1a1 in vivo and in vitro. Fibrosis gene array analyses revealed an upregulation of 35 fibrotic genes in AA injured mice. Treatment with HLSC-EVs downregulated 14 fibrotic genes in total, out of which 5 were upregulated in mice injured with AA. Analyses of the total mouse miRnome identified several microRNAs involved in the regulation of fibrotic pathways which were found to be modulated post treatment with HLSC-EVs. These results indicate that HLSC-EVs play a regenerative role in CKD possibly through the regulation of genes and microRNAs that are activated during the progression of the disease.

  • Data_Sheet_1_Human Liver Stem Cell-Derived ExtraCellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis.docx
    2018
    Co-Authors: Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
    Abstract:

    With limited therapeutic intervention in preventing the progression to end-stage renal disease, chronic kidney disease (CKD) remains a global health-care burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury, and interstitial fibrosis. Human Liver Stem Cell-derived extraCellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA-induced mouse model of CKD. NSG mice were injected with HLSC-EVs 3 days after administering AA on a weekly basis for 4 weeks. Mice injected with AA significantly lost weight over the 4-week period. Deterioration in kidney function was also observed. Histology was performed to evaluate tubular necrosis, interstitial fibrosis, as well as infiltration of inflammatory Cells/fibroblasts. Kidneys were also subjected to gene array analyses to evaluate regulation of microRNAs (miRNAs) and pro-fibrotic genes. The effect of HLSC-EVs was also tested in vitro to assess pro-fibrotic gene regulation in fibroblasts cocultured with AA pretreated tubular epithelial Cells. Histological analyses showed that treatment with HLSC-EVs significantly reduced tubular necrosis, interstitial fibrosis, infiltration of CD45 Cells and fibroblasts, which were all elevated during AA induced injury. At a molecular level, HLSC-EVs significantly inhibited the upregulation of the pro-fibrotic genes α-Sma, Tgfb1, and Col1a1 in vivo and in vitro. Fibrosis gene array analyses revealed an upregulation of 35 pro-fibrotic genes in AA injured mice. Treatment with HLSC-EVs downregulated 14 pro-fibrotic genes in total, out of which, 5 were upregulated in mice injured with AA. Analyses of the total mouse miRnome identified several miRNAs involved in the regulation of fibrotic pathways, which were found to be modulated post-treatment with HLSC-EVs. These results indicate that HLSC-EVs play a regenerative role in CKD possibly through the regulation of genes and miRNAs that are activated during the progression of the disease.

  • human Liver Stem Cell derived microvesicles accelerate hepatic regeneration in hepatectomized rats
    Journal of Cellular and Molecular Medicine, 2009
    Co-Authors: Mb Herrera, Maria Chiara Deregibus, Ciro Tetta, Valentina Fonsato, S Gatti, Andrea Sordi, Daniela Cantarella, Raffaele A Calogero, Benedetta Bussolati, Giovanni Camussi
    Abstract:

    Several studies indicate that adult Stem Cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident Cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human Liver Stem Cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an α4-integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of Cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of Liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the Liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.

Lola M. Reid - One of the best experts on this subject based on the ideXlab platform.

  • regulation of hepatic Stem progenitor phenotype by microenvironment stiffness in hydrogel models of the human Liver Stem Cell niche
    Biomaterials, 2011
    Co-Authors: Oswaldo A Lozoya, Eliane Wauthier, Lola M. Reid, Rachael Turner, Claire Barbier, Glenn D Prestwich, Farshid Guilak, Richard Superfine, Sharon R Lubkin
    Abstract:

    Human Livers have maturational lineages of Cells within Liver acini, beginning periportally in Stem Cell niches, the canals of Hering, and ending in polyploid hepatocytes pericentrally and cholangiocytes in bile ducts. Hepatic Stem Cells (hHpSCs) in vivo are partnered with mesenchymal precursors to endothelia (angioblasts) and stellate Cells, and reside in regulated microenvironments, Stem Cell niches, containing hyaluronans (HA). The in vivo hHpSC niche is modeled in vitro by growing hHpSC in two-dimensional (2D) cultures on plastic. We investigated effects of 3D microenvironments, mimicking the Liver’s Stem Cell niche, on these hHpSCs by embedding them in HA-based hydrogels prepared with Kubota’s Medium (KM), a serum-free medium tailored for endodermal Stem/progenitors. The KM-HA hydrogels mimicked the niches, matched diffusivity of culture medium, exhibited shear thinning and perfect elasticity under mechanical loading, and had predictable stiffness depending on their chemistry. KM-HA hydrogels, which supported Cell attachment, survival and expansion of hHpSC colonies, induced transition of hHpSC colonies towards stable heterogeneous populations of hepatic progenitors depending on KM-HA hydrogel stiffness, as shown by both their gene and protein expression profile. These acquired phenotypes did not show morphological evidence of fibrotic responses. In conclusion, this study shows that the mechanical properties of the microenvironment can regulate differentiation in endodermal Stem Cell populations.

Ciro Tetta - One of the best experts on this subject based on the ideXlab platform.

  • human Liver Stem Cell derived extraCellular vesicles prevent aristolochic acid induced kidney fibrosis
    Frontiers in Immunology, 2018
    Co-Authors: Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
    Abstract:

    With limited therapeutic intervention in preventing the progression to end stage renal disease, chronic kidney disease (CKD) remains a global healthcare burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury and interstitial fibrosis. Human Liver Stem Cell derived extraCellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA induced mouse model of CKD. NSG mice were injected with HLSC-EVs three days after administering AA on a weekly basis for four weeks. Mice injected with AA significantly lost weight over the four week period. Deterioration in kidney function was also observed. Histology was performed to evaluate tubular necrosis, interstitial fibrosis, as well as infiltration of inflammatory Cells/fibroblasts. Kidneys were also subjected to genetic array analyses to evaluate regulation of microRNAs and fibrotic genes. The effect of HLSC-EVs was also tested in vitro to assess fibrotic gene regulation in fibroblasts co-cultured with AA treated tubular epithelial Cells. Histological analyses showed that treatment with HLSC-EVs significantly reduced tubular necrosis, interstitial fibrosis, infiltration of CD45 Cells and fibroblasts which were all elevated during AA induced injury. At a molecular level, HLSC-EVs significantly inhibited the upregulation of the fibrotic genes α-Sma, Tgfb1 and Col1a1 in vivo and in vitro. Fibrosis gene array analyses revealed an upregulation of 35 fibrotic genes in AA injured mice. Treatment with HLSC-EVs downregulated 14 fibrotic genes in total, out of which 5 were upregulated in mice injured with AA. Analyses of the total mouse miRnome identified several microRNAs involved in the regulation of fibrotic pathways which were found to be modulated post treatment with HLSC-EVs. These results indicate that HLSC-EVs play a regenerative role in CKD possibly through the regulation of genes and microRNAs that are activated during the progression of the disease.

  • Data_Sheet_1_Human Liver Stem Cell-Derived ExtraCellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis.docx
    2018
    Co-Authors: Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
    Abstract:

    With limited therapeutic intervention in preventing the progression to end-stage renal disease, chronic kidney disease (CKD) remains a global health-care burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury, and interstitial fibrosis. Human Liver Stem Cell-derived extraCellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA-induced mouse model of CKD. NSG mice were injected with HLSC-EVs 3 days after administering AA on a weekly basis for 4 weeks. Mice injected with AA significantly lost weight over the 4-week period. Deterioration in kidney function was also observed. Histology was performed to evaluate tubular necrosis, interstitial fibrosis, as well as infiltration of inflammatory Cells/fibroblasts. Kidneys were also subjected to gene array analyses to evaluate regulation of microRNAs (miRNAs) and pro-fibrotic genes. The effect of HLSC-EVs was also tested in vitro to assess pro-fibrotic gene regulation in fibroblasts cocultured with AA pretreated tubular epithelial Cells. Histological analyses showed that treatment with HLSC-EVs significantly reduced tubular necrosis, interstitial fibrosis, infiltration of CD45 Cells and fibroblasts, which were all elevated during AA induced injury. At a molecular level, HLSC-EVs significantly inhibited the upregulation of the pro-fibrotic genes α-Sma, Tgfb1, and Col1a1 in vivo and in vitro. Fibrosis gene array analyses revealed an upregulation of 35 pro-fibrotic genes in AA injured mice. Treatment with HLSC-EVs downregulated 14 pro-fibrotic genes in total, out of which, 5 were upregulated in mice injured with AA. Analyses of the total mouse miRnome identified several miRNAs involved in the regulation of fibrotic pathways, which were found to be modulated post-treatment with HLSC-EVs. These results indicate that HLSC-EVs play a regenerative role in CKD possibly through the regulation of genes and miRNAs that are activated during the progression of the disease.

  • human Liver Stem Cell derived microvesicles inhibit hepatoma growth in scid mice by deLivering antitumor micrornas
    Stem Cells, 2012
    Co-Authors: Valentina Fonsato, Maria Chiara Deregibus, Federica Collino, Maria Beatriz Herrera, Claudia Cavallari, Barbara Cisterna, Stefania Bruno, Renato Romagnoli, Mauro Salizzoni, Ciro Tetta
    Abstract:

    Microvesicles (MVs) play a pivotal role in Cell-to-Cell communication. Recent studies demonstrated that MVs may transfer genetic information between Cells. Here, we show that MVs derived from human adult Liver Stem Cells (HLSC) may reprogram in vitro HepG2 hepatoma and primary hepatoCellular carcinoma Cells by inhibiting their growth and survival. In vivo intratumor administration of MVs induced regression of ectopic tumors developed in SCID mice. We suggest that the mechanism of action is related to the deLivery of microRNAs (miRNAs) from HLSC-derived MVs (MV-HLSC) to tumor Cells on the basis of the following evidence: (a) the rapid, CD29-mediated internalization of MV-HLSC in HepG2 and the inhibition of tumor Cell growth after MV uptake; (b) the transfer by MV-HLSC of miRNAs with potential antitumor activity that was downregulated in HepG2 Cells with respect to normal hepatocytes; (c) the abrogation of the MV-HLSC antitumor effect after MV pretreatment with RNase or generation of MVs depleted of miRNAs; (d) the relevance of selected miRNAs was proven by transfecting HepG2 with miRNA mimics. The antitumor effect of MV-HLSC was also observed in tumors other than Liver such as lymphoblastoma and glioblastoma. These results suggest that the deLivery of selected miRNAs by MVs derived from Stem Cells may inhibit tumor growth and stimulate apoptosis. Stem Cells2012;30:1985–1998

  • human Liver Stem Cell derived microvesicles accelerate hepatic regeneration in hepatectomized rats
    Journal of Cellular and Molecular Medicine, 2009
    Co-Authors: Mb Herrera, Maria Chiara Deregibus, Ciro Tetta, Valentina Fonsato, S Gatti, Andrea Sordi, Daniela Cantarella, Raffaele A Calogero, Benedetta Bussolati, Giovanni Camussi
    Abstract:

    Several studies indicate that adult Stem Cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident Cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human Liver Stem Cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an α4-integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of Cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of Liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the Liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.

Maria Chiara Deregibus - One of the best experts on this subject based on the ideXlab platform.

  • human Liver Stem Cell derived extraCellular vesicles prevent aristolochic acid induced kidney fibrosis
    Frontiers in Immunology, 2018
    Co-Authors: Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
    Abstract:

    With limited therapeutic intervention in preventing the progression to end stage renal disease, chronic kidney disease (CKD) remains a global healthcare burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury and interstitial fibrosis. Human Liver Stem Cell derived extraCellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA induced mouse model of CKD. NSG mice were injected with HLSC-EVs three days after administering AA on a weekly basis for four weeks. Mice injected with AA significantly lost weight over the four week period. Deterioration in kidney function was also observed. Histology was performed to evaluate tubular necrosis, interstitial fibrosis, as well as infiltration of inflammatory Cells/fibroblasts. Kidneys were also subjected to genetic array analyses to evaluate regulation of microRNAs and fibrotic genes. The effect of HLSC-EVs was also tested in vitro to assess fibrotic gene regulation in fibroblasts co-cultured with AA treated tubular epithelial Cells. Histological analyses showed that treatment with HLSC-EVs significantly reduced tubular necrosis, interstitial fibrosis, infiltration of CD45 Cells and fibroblasts which were all elevated during AA induced injury. At a molecular level, HLSC-EVs significantly inhibited the upregulation of the fibrotic genes α-Sma, Tgfb1 and Col1a1 in vivo and in vitro. Fibrosis gene array analyses revealed an upregulation of 35 fibrotic genes in AA injured mice. Treatment with HLSC-EVs downregulated 14 fibrotic genes in total, out of which 5 were upregulated in mice injured with AA. Analyses of the total mouse miRnome identified several microRNAs involved in the regulation of fibrotic pathways which were found to be modulated post treatment with HLSC-EVs. These results indicate that HLSC-EVs play a regenerative role in CKD possibly through the regulation of genes and microRNAs that are activated during the progression of the disease.

  • Data_Sheet_1_Human Liver Stem Cell-Derived ExtraCellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis.docx
    2018
    Co-Authors: Sharad Kholia, Maria Beatriz Herrera Sanchez, Massimo Cedrino, Elli Papadimitriou, Marta Tapparo, Maria Chiara Deregibus, Maria Felice Brizzi, Ciro Tetta, Giovanni Camussi
    Abstract:

    With limited therapeutic intervention in preventing the progression to end-stage renal disease, chronic kidney disease (CKD) remains a global health-care burden. Aristolochic acid (AA) induced nephropathy is a model of CKD characterised by inflammation, tubular injury, and interstitial fibrosis. Human Liver Stem Cell-derived extraCellular vesicles (HLSC-EVs) have been reported to exhibit therapeutic properties in various disease models including acute kidney injury. In the present study, we aimed to investigate the effects of HLSC-EVs on tubular regeneration and interstitial fibrosis in an AA-induced mouse model of CKD. NSG mice were injected with HLSC-EVs 3 days after administering AA on a weekly basis for 4 weeks. Mice injected with AA significantly lost weight over the 4-week period. Deterioration in kidney function was also observed. Histology was performed to evaluate tubular necrosis, interstitial fibrosis, as well as infiltration of inflammatory Cells/fibroblasts. Kidneys were also subjected to gene array analyses to evaluate regulation of microRNAs (miRNAs) and pro-fibrotic genes. The effect of HLSC-EVs was also tested in vitro to assess pro-fibrotic gene regulation in fibroblasts cocultured with AA pretreated tubular epithelial Cells. Histological analyses showed that treatment with HLSC-EVs significantly reduced tubular necrosis, interstitial fibrosis, infiltration of CD45 Cells and fibroblasts, which were all elevated during AA induced injury. At a molecular level, HLSC-EVs significantly inhibited the upregulation of the pro-fibrotic genes α-Sma, Tgfb1, and Col1a1 in vivo and in vitro. Fibrosis gene array analyses revealed an upregulation of 35 pro-fibrotic genes in AA injured mice. Treatment with HLSC-EVs downregulated 14 pro-fibrotic genes in total, out of which, 5 were upregulated in mice injured with AA. Analyses of the total mouse miRnome identified several miRNAs involved in the regulation of fibrotic pathways, which were found to be modulated post-treatment with HLSC-EVs. These results indicate that HLSC-EVs play a regenerative role in CKD possibly through the regulation of genes and miRNAs that are activated during the progression of the disease.

  • human Liver Stem Cell derived microvesicles inhibit hepatoma growth in scid mice by deLivering antitumor micrornas
    Stem Cells, 2012
    Co-Authors: Valentina Fonsato, Maria Chiara Deregibus, Federica Collino, Maria Beatriz Herrera, Claudia Cavallari, Barbara Cisterna, Stefania Bruno, Renato Romagnoli, Mauro Salizzoni, Ciro Tetta
    Abstract:

    Microvesicles (MVs) play a pivotal role in Cell-to-Cell communication. Recent studies demonstrated that MVs may transfer genetic information between Cells. Here, we show that MVs derived from human adult Liver Stem Cells (HLSC) may reprogram in vitro HepG2 hepatoma and primary hepatoCellular carcinoma Cells by inhibiting their growth and survival. In vivo intratumor administration of MVs induced regression of ectopic tumors developed in SCID mice. We suggest that the mechanism of action is related to the deLivery of microRNAs (miRNAs) from HLSC-derived MVs (MV-HLSC) to tumor Cells on the basis of the following evidence: (a) the rapid, CD29-mediated internalization of MV-HLSC in HepG2 and the inhibition of tumor Cell growth after MV uptake; (b) the transfer by MV-HLSC of miRNAs with potential antitumor activity that was downregulated in HepG2 Cells with respect to normal hepatocytes; (c) the abrogation of the MV-HLSC antitumor effect after MV pretreatment with RNase or generation of MVs depleted of miRNAs; (d) the relevance of selected miRNAs was proven by transfecting HepG2 with miRNA mimics. The antitumor effect of MV-HLSC was also observed in tumors other than Liver such as lymphoblastoma and glioblastoma. These results suggest that the deLivery of selected miRNAs by MVs derived from Stem Cells may inhibit tumor growth and stimulate apoptosis. Stem Cells2012;30:1985–1998

  • human Liver Stem Cell derived microvesicles accelerate hepatic regeneration in hepatectomized rats
    Journal of Cellular and Molecular Medicine, 2009
    Co-Authors: Mb Herrera, Maria Chiara Deregibus, Ciro Tetta, Valentina Fonsato, S Gatti, Andrea Sordi, Daniela Cantarella, Raffaele A Calogero, Benedetta Bussolati, Giovanni Camussi
    Abstract:

    Several studies indicate that adult Stem Cells may improve the recovery from acute tissue injury. It has been suggested that they may contribute to tissue regeneration by the release of paracrine factors promoting proliferation of tissue resident Cells. However, the factors involved remain unknown. In the present study we found that microvesicles (MVs) derived from human Liver Stem Cells (HLSC) induced in vitro proliferation and apoptosis resistance of human and rat hepatocytes. These effects required internalization of MVs in the hepatocytes by an α4-integrin-dependent mechanism. However, MVs pre-treated with RNase, even if internalized, were unable to induce hepatocyte proliferation and apoptosis resistance, suggesting an RNA-dependent effect. Microarray analysis and quantitative RT-PCR demonstrated that MVs were shuttling a specific subset of Cellular mRNA, such as mRNA associated in the control of transcription, translation, proliferation and apoptosis. When administered in vivo, MVs accelerated the morphological and functional recovery of Liver in a model of 70% hepatectomy in rats. This effect was associated with increase in hepatocyte proliferation and was abolished by RNase pre-treatment of MVs. Using human AGO2, as a reporter gene present in MVs, we found the expression of human AGO2 mRNA and protein in the Liver of hepatectomized rats treated with MVs. These data suggested a translation of the MV shuttled mRNA into hepatocytes of treated rats. In conclusion, these results suggest that MVs derived from HLSC may activate a proliferative program in remnant hepatocytes after hepatectomy by a horizontal transfer of specific mRNA subsets.

Bernd J. Helms - One of the best experts on this subject based on the ideXlab platform.

  • long term adult feline Liver organoid cultures for disease modeling of hepatic steatosis
    Stem cell reports, 2017
    Co-Authors: Hedwig S. Kruitwagen, Monique E Van Wolferen, Loes A. Oosterhoff, Ingrid G.w.h. Vernooij, Ingrid M. Schrall, Farah Bannink, Camille Roesch, Lisa Van Uden, Martijn R. Molenaar, Bernd J. Helms
    Abstract:

    Hepatic steatosis is a highly prevalent Liver disease, yet research is hampered by the lack of tractable Cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of Liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline Liver organoid culture with adult Liver Stem Cell characteristics and differentiation potential toward hepatocyte-like Cells. Next, organoids from mouse, human, dog, and cat Liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline Liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline Liver organoids. In conclusion, feline Liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research.

  • Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis
    Elsevier, 2017
    Co-Authors: Hedwig S. Kruitwagen, Monique E Van Wolferen, Loes A. Oosterhoff, Ingrid G.w.h. Vernooij, Ingrid M. Schrall, Farah Bannink, Camille Roesch, Lisa Van Uden, Martijn R. Molenaar, Bernd J. Helms
    Abstract:

    Summary: Hepatic steatosis is a highly prevalent Liver disease, yet research is hampered by the lack of tractable Cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of Liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline Liver organoid culture with adult Liver Stem Cell characteristics and differentiation potential toward hepatocyte-like Cells. Next, organoids from mouse, human, dog, and cat Liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline Liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline Liver organoids. In conclusion, feline Liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research. : In this study Kruitwagen and colleagues establish and characterize a feline Liver organoid culture, which has adult Stem Cell properties and can be differentiated toward hepatocyte-like Cells. They propose Liver organoids as a tool to model hepatic steatosis and show that feline Liver organoids accumulate more lipids than human organoids when provided with excess fatty acids. Keywords: feline Liver organoids, adult Liver Stem Cells, hepatic steatosis, disease modeling, feline hepatic lipidosis, species difference