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Paul A Dawson - One of the best experts on this subject based on the ideXlab platform.

Marco Montagnani - One of the best experts on this subject based on the ideXlab platform.

Matthias Stelzner - One of the best experts on this subject based on the ideXlab platform.

  • Treatment of Bile Acid Malabsorption Using Ileal Stem Cell Transplantation
    Journal of the American College of Surgeons, 2005
    Co-Authors: Jeffrey R. Avansino, David C. Chen, Vicki D. Hoagland, Jacob D. Woolman, W. Geoffrey Haigh, Matthias Stelzner
    Abstract:

    Background We hypothesized that ileal stem cell clusters transplanted into a segment of jejunum can be used to treat Bile Acid Malabsorption. Study design In adult Lewis rats, a 15-cm segment of jejunum was isolated with its blood circulation left intact and partially stripped of enterocytes using luminal high-velocity perfusions with 3mmol/L ethylenediamine tetra-acetic Acid solutions. Continuity was restored by anastomosing the proximal and distal gut. Ileal stem cell clusters were harvested from neonatal Lewis rats and transplanted into the stripped segments to generate a "neoileum." After 4weeks, recipients underwent resection of the native ileum, and the isolated neoileum was anastomosed in its place. After an additional 4weeks, a 48-hour stool collection was performed. The engrafted segment was harvested for taurocholate uptake studies, ileal Bile Acid transporter (IBAT) protein by immunohistomorphometry, and IBAT mRNA quantitation by reverse transcription polymerease chain reaction. Data were analyzed by ANOVA/ t -test. Rats undergoing ileectomy, jejunectomy, or sham operations served as controls. Results Total Bile Acid loss in the stool was markedly lower in rats with a neoileum compared with rats with an ileectomy (p Conclusions Ileal stem cell clusters were used to establish a new zone of Bile Acid uptake and IBAT expression in a jejunal segment. This neoileum eliminated loss of Bile Acids in the stool after ileectomy. This is the first time that transplantation of intestinal stem cell clusters has been shown to correct a clinical Malabsorption syndrome.

  • Treatment of Bile Acid Malabsorption using ileal stem cell transplantation
    Journal of Surgical Research, 2003
    Co-Authors: Jeffrey R. Avansino, Vicki D. Hoagland, Jacob D. Woolman, W. Geoffrey Haigh, Matthias Stelzner
    Abstract:

    Purpose: To determine if ileal stem cells transplanted into a segment of jejunum can be used to treat Bile Acid Malabsorption. Methods: In adult Lewis rats, a 15-cm segment of jejunum was isolated with its blood circulation left intact and partially stripped of enterocytes using luminal high-velocity perfusions with 3 mM EDTA solutions. Continuity was restored by anastomosing the proximal and distal gut. Ileal stem cell clusters were harvested from neo-natal Lewis rats and transplanted into these segments. After 4 weeks, rats underwent an ileectomy and the isolated segment was anastomosed in its place. After an additional 4 weeks, a 48 hour stool collection was performed. The engrafted segment was harvested for taurocholate uptake studies, ileal Bile Acid transporter (IBAT) protein (by immunohistomorphometry) and IBAT mRNA quantitation (by RT-PCR). Data was analyzed by ANOVA/t-test. Rats undergoing ileectomy, jejunectomy or sham operation served as controls. Results: Total Bile Acid loss in the stool was significantly lower in rats with a neo-ileum compared to rats with an ileectomy (p < 0.004; Fig. 1). Na+-dependent taurocholate uptake was significantly increased in the neo-ileum compared to the jejunum (p < 0.001). IBAT protein signal intensity was significantly higher in the neo-ileum compared to jejunum (p < 0.001). IBAT mRNA amounts were significantly higher (p < 0.004) than in the jejunum however comparable to the ileum. Conclusion: Ileal stem cells were used to establish a new zone of active Bile Acid uptake and IBAT expression in a jejunal segment. This neo-ileum eliminated loss of Bile Acids in the stool after ileectomy. This is the first time intestinal stem cell transplantation has been shown to correct a clinical Malabsorption syndrome. Download high-res image (132KB) Download full-size image

  • Systemic effects of acute terminal ileitis on uninflamed gut aggravate Bile Acid Malabsorption.
    The Journal of surgical research, 2001
    Co-Authors: Matthias Stelzner, Sivagurunathan Somasundaram, Temur Khakberdiev
    Abstract:

    Abstract Background. Some patients with terminal ileitis suffer from significant Bile Acid Malabsorption even if the inflammation is locally limited. We hypothesized that inflammation in the terminal ileum may lead to changes in mucosal absorption in more proximal intestinal segments and aggravate Bile Acid Malabsorption. Methods. Five hamsters underwent laparotomy and localized instillation of 2,4,6-trinitrobenzenesulfonic Acid (TNBS) in 10% ethanol into the last 4 cm of ileum to create terminal ileitis. A control group (n = 5) underwent instillation of saline. Animals were sacrificed after 24 h. Active and passive transport of radiolabeled Bile Acids was measured in the proximal and terminal ileum and glucose absorption in the jejunum using an everted sleeve technique. Myeloperoxidase (MPO) activity and histomorphology were examined by standard methods. Results. In animals with ileitis, active Bile Acid uptake decreased by 84% in the terminal ileum (t test, P Conclusion. These data suggest that limited acute ileitis impairs active Bile Acid uptake in the terminal ileum. It also diminishes active Bile Acid and glucose absorption in more proximal segments of the small intestine, likely by a systemic effect. This systemic effect may aggravate Bile Acid Malabsorption in patients with limited ileitis.

Gösta Eggertsen - One of the best experts on this subject based on the ideXlab platform.

Elisa Ravaioli - One of the best experts on this subject based on the ideXlab platform.