• 2015-10-06

    Reduction of Liver Fibrosis by Xenogeneic Human Umbilical Cord Blood and Adipose Tissue-derived Multipotent Stem Cells without Treatment of an Immunosuppressant

    요약 : 
    Therapy using stem cells for the liver fibrosis is a prospective alternative to overcome the insufficiency of transplantable liver donor. Here, we demonstrated xenogeneic human cell therapy for the treatment of rat liver
    fibrosis without the use of an immunosuppressant. Liver fibrosis was induced by dimethylnitrosamine for 5 weeks in six-week-old male Sprague-Dawley rats. Human umbilical cord blood- and adipose tissue-derived multipotent stem cells were injected intravenously by the tail vein after one week. Blood samples were collected and liver samples were stained with Masson’s trichrome in order to evaluate the amount of fibrosis. After the cell injection, the level of total protein, albumin, alanine transaminase and aspartic acid transaminase was recovered to the similar level of the normal rats. The liver weight per body weight increased after the cell injection. Collagen fiber, near the portal triad and marginal region, was reduced, significantly. Taken together, it is suggested that xenotransplantation of multipotent stem cells might be a candidate for the treatment of liver fibrosis without the use of an immunosuppresant

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    • 2015-10-06

    Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation.

    요약 : 
    Objective. To investigate the efficacy of human adipose tissue–derived mesenchymal stem cell (ADMSC) transplantation in systemic lupus erythematosus (SLE) and to determine the optimal transplantation
    window for stem cells either before or after disease onset.
    Methods. (NZB NZW)F1 mice with SLE were administered human AD-MSCs (5 105) intravenously every 2 weeks from age 6 weeks until age 60 weeks, while the control group received saline vehicle on the same schedule. Another experiment was carried out with a different initiation time point for serial transplantation (age 6 weeks or age 32 weeks).
    Results. Long-term serial administration (total of 28 times) of human AD-MSCs ameliorated SLE without any adverse effects. Compared with the control group, the human AD-MSC–treated group had a significantly
    higher survival rate with improvement of histologic and serologic abnormalities and immunologic function, and also had a decreased incidence of proteinuria. Anti–double-stranded DNA antibodies and blood urea nitrogen levels decreased significantly with transplantation of human AD-MSCs, and serum levels of granulocyte–macrophage colony-stimulating factor, interleukin-4 (IL-4), and IL-10 increased significantly. A significant
    increase in the proportion of CD4 FoxP3 cells and a marked restoration of capacity for cytokine production were observed in spleens from the human AD-MSC–treated group. In the second experiment, an early stage
    treatment group showed better results (higher survival rates and lower incidence of proteinuria) than an advanced stage treatment group.
    Conclusion. Serial human AD-MSC transplantation had beneficial effects in the treatment of SLE, without adverse effects. Transplantation of human ADMSCs before disease onset was preferable for amelioration of SLE and restoration of immune homeostasis.

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    • 2015-10-06

    Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans.

    요약 :
    Adipose tissue-derived mesenchymal stem cells (AdMSCs) represent an attractive and ethical cell source for stem cell therapy. With the recent demonstration of MSC homing properties, intravenous applications of MSCs
    to cell-damaged diseases have increased. In the present study, the toxicity and tumorigenicity of human AdMSCs (hAdMSCs) were investigated for clinical application. Culture-expanded hAdMSCs showed the typical
    appearance, immunophenotype, and differentiation capacity of MSCs, and were genetically stable at least 12 passages in culture. Cells suspended in physiological saline maintained their MSC properties in a cold storage
    condition for at least 3 days. To test the toxicity of hAdMSCs, different doses of hAdMSCs were injected intravenously into immunodeficient mice, and the mice were observed for 13 weeks. Even at the highest cell
    dose (2.5 · 108 cells/kg body weight), the SCID mice were viable and had no side effects. A tumorigenicity test was performed in Balb/c-nu nude mice for 26 weeks. Even at the highest cell dose (2 · 108 MSCs/kg), no
    evidence of tumor development was found. In a human clinical trial, 8 male patients who had suffered a spinal cord injury > 12 months previous were intravenously administered autologous hAdMSCs (4 · 108 cells) one
    time. None of the patients developed any serious adverse events related to hAdMSC transplantation during the 3-month follow-up. In conclusion, the systemic transplantation of hAdMSCs appears to be safe and does not
    induce tumor development

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    • 2015-04-07

    Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations.

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