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Marhaen Hardjo - One of the best experts on this subject based on the ideXlab platform.

  • suppression of carbon tetrachloride induced liver fibrosis by transplantation of a clonal Mesenchymal Stem Cell line derived from rat bone marrow
    Cell Transplantation, 2009
    Co-Authors: Marhaen Hardjo, Takuro Masaka, Masahiro Miyazaki, Masakiyo Sakaguchi, Sukaeni Ibrahim, Ken Kataoka, Nam Ho Huh
    Abstract:

    Transplantation of hepatocytes or bone marrow-derived Cells has been shown to ameliorate liver fibrosis in animal models, but no direct comparison of relative efficiency has been made. The aim of this study was to compare the efficiency of a bone marrow-derived clonal Mesenchymal Stem Cell line established by us (rBM25/S3) with that of its adipogenic or hepatogenic differentiation derivative for suppression of rat liver fibrosis. After induction of differentiation of rBM25/S3 Cells into adipogenic or hepatogenic Cells in culture, we intrasplenically transplanted the three types of Cells into rats (3 x 10(7) Cells/rat) before and 4 weeks after initiation of carbon tetrachloride treatment (1 ml/kg body weight twice a week for 8 weeks) to induce liver fibrosis. Undifferentiated rBM25/S3 Cells were the most effective for suppression of liver fibrosis, followed by the adipogenic Cells and hepatogenic Cells. Expression levels of MMP-2 and MMP-9 were also highest in undifferentiated rBM25/S3 Cells. These results indicate that bone marrow-derived clonal Mesenchymal Stem Cell lines are useful for further mechanistic studies on Cell-mediated suppression of liver fibrosis and that such Cell lines will provide information on an appropriate Cell source for transplantation therapy for cirrhosis.

  • suppression of carbon tetrachloride induced liver fibrosis by transplantation of a clonal Mesenchymal Stem Cell line derived from rat bone marrow
    Cell Transplantation, 2009
    Co-Authors: Marhaen Hardjo, Takuro Masaka, Masahiro Miyazaki, Masakiyo Sakaguchi, Sukaeni Ibrahim, Ken Kataoka
    Abstract:

    : Transplantation of hepatocytes or bone marrow-derived Cells has been shown to ameliorate liver fibrosis in animal models, but no direct comparison of relative efficiency has been made. The aim of this study was to compare the efficiency of a bone marrow-derived clonal Mesenchymal Stem Cell line established by us (rBM25/S3) with that of its adipogenic or hepatogenic differentiation derivative for suppression of rat liver fibrosis. After induction of differentiation of rBM25/S3 Cells into adipogenic or hepatogenic Cells in culture, we intrasplenically transplanted the three types of Cells into rats (3 x 10(7) Cells/rat) before and 4 weeks after initiation of carbon tetrachloride treatment (1 ml/kg body weight twice a week for 8 weeks) to induce liver fibrosis. Undifferentiated rBM25/S3 Cells were the most effective for suppression of liver fibrosis, followed by the adipogenic Cells and hepatogenic Cells. Expression levels of MMP-2 and MMP-9 were also highest in undifferentiated rBM25/S3 Cells. These results indicate that bone marrow-derived clonal Mesenchymal Stem Cell lines are useful for further mechanistic studies on Cell-mediated suppression of liver fibrosis and that such Cell lines will provide information on an appropriate Cell source for transplantation therapy for cirrhosis.

Thomas V Johnson - One of the best experts on this subject based on the ideXlab platform.

  • identification of retinal ganglion Cell neuroprotection conferred by platelet derived growth factor through analysis of the Mesenchymal Stem Cell secretome
    Brain, 2014
    Co-Authors: Thomas V Johnson, Nicholas W Dekorver, Victoria A Levasseur, Andrew Osborne, Alessia Tassoni, Barbara Lorber, Janosch P Heller, Rafael Villasmil
    Abstract:

    The development of neuroprotective strategies to attenuate retinal ganglion Cell death could lead to novel therapies for chronic optic neuropathies such as glaucoma. Intravitreal transplantation of Mesenchymal Stem Cells slows retinal ganglion Cell death in models of optic nerve injury, but the mechanism of action remains unclear. Here we characterized the neuroprotective effects of Mesenchymal Stem Cells and Mesenchymal Stem Cell-derived factors in organotypic retinal explant culture and an in vivo model of ocular hypertensive glaucoma. Co-culture of rat and human bone marrow-derived Mesenchymal Stem Cells with retinal explants increased retinal ganglion Cell survival, after 7 days ex vivo, by ∼2-fold and was associated with reduced apoptosis and increased nerve fibre layer and inner plexiform layer thicknesses. These effects were not demonstrated by co-culture with human or mouse fibroblasts. Conditioned media from Mesenchymal Stem Cells conferred neuroprotection, suggesting that the neuroprotection is mediated, at least partly, by secreted factors. We compared the concentrations of 29 factors in human Mesenchymal Stem Cell and fibroblast conditioned media, and identified 11 enriched in the Mesenchymal Stem Cell secretome. Treatment of retinal explants with a cocktail of these factors conferred retinal ganglion Cell neuroprotection, with factors from the platelet-derived growth factor family being the most potent. Blockade of platelet-derived growth factor signalling with neutralizing antibody or with small molecule inhibitors of platelet-derived growth factor receptor kinase or downstream phosphatidylinositol 3 kinase eliminated retinal ganglion Cell neuroprotection conferred by Mesenchymal Stem Cell co-culture. Intravitreal injection of platelet-derived growth factor -AA or -AB led to profound optic nerve neuroprotection in vivo following experimental induction of elevated intraocular pressure. These data demonstrate that Mesenchymal Stem Cells secrete a number of neuroprotective proteins and suggest that platelet-derived growth factor secretion in particular may play an important role in Mesenchymal Stem Cell-mediated retinal ganglion Cell neuroprotection. Furthermore, platelet-derived growth factor may represent an independent target for achieving retinal ganglion Cell neuroprotection.

  • neuroprotective effects of intravitreal Mesenchymal Stem Cell transplantation in experimental glaucoma
    Investigative Ophthalmology & Visual Science, 2010
    Co-Authors: Thomas V Johnson, Natalie D Bull, David Hunt, Nephtali Marina, Stanislav I Tomarev, Keith R Martin
    Abstract:

    Purpose. Retrograde neurotrophic factor transport blockade has been implicated in the pathophysiology of glaucoma. Stem Cell transplantation appears to ameliorate some neurodegenerative conditions in the brain and spinal cord, in part by neurotrophic factor secretion. The present study was conducted to determine whether local or syStemic bone marrow-derived Mesenchymal Stem Cell (MSC) transplantation can confer neuroprotection in a rat model of laser-induced ocular hypertensive glaucoma.

Soo Young Choe - One of the best experts on this subject based on the ideXlab platform.

Jingping Sun - One of the best experts on this subject based on the ideXlab platform.

Richard O C Oreffo - One of the best experts on this subject based on the ideXlab platform.

  • nanoscale surfaces for the long term maintenance of Mesenchymal Stem Cell phenotype and multipotency
    Nature Materials, 2011
    Co-Authors: Rebecca J Mcmurray, Nikolaj Gadegaard, Monica P Tsimbouri, Karl Urgess, Laura E Mcnamara, Rahul S Tare, Kate Murawski, Emmajayne Kingham, Richard O C Oreffo
    Abstract:

    There is currently an unmet need for the supply of autologous, patient-specific Stem Cells for regenerative therapies in the clinic. Mesenchymal Stem Cell differentiation can be driven by the material/Cell interface suggesting a unique strategy to manipulate Stem Cells in the absence of complex soluble chemistries or Cellular reprogramming. However, so far the derivation and identification of surfaces that allow retention of multipotency of this key regenerative Cell type have remained elusive. Adult Stem Cells spontaneously differentiate in culture, resulting in a rapid diminution of the multipotent Cell population and their regenerative capacity. Here we identify a nanostructured surface that retains Stem-Cell phenotype and maintains Stem-Cell growth over eight weeks. Furthermore, the study implicates a role for small RNAs in repressing key Cell signalling and metabolomic pathways, demonstrating the potential of surfaces as non-invasive tools with which to address the Stem Cell niche.