Hepatocellular heme oxygenase-1: a potential mechanism of erythropoietin-mediated protection after liver ischemia-reperfusion injury.

Hepatic ischemia-reperfusion (IR) results in progressive injury; initiated by oxidative stress during ischemia and compounded by cytokine-mediated inflammation during reperfusion. Recovery requires strict regulation of these events. Recombinant human erythropoietin (rhEPO) is thought to mitigate hepatocellular IR injury by altering the nonparenchymal liver microenvironment.

Suppressor of cytokine signaling expression with increasing severity of murine hepatic ischemia-reperfusion injury.

Background/aims: Preservation of function requires tight regulation of the cellular events initiated when hepatic ischemia is followed by reperfusion (IR). One important mechanism modulating the cytokine-directed response to injury is Suppressors of Cytokine Signaling. SOCS1 and SOCS3 ensure appropriate intensity and duration of cytokine signaling through negative feedback on JAK-STAT signaling.

Comparison of polyester scaffolds for bioengineered intestinal mucosa.

Introduction: Biodegradable polyester scaffolds have proven useful for growing neointestinal tissue equivalents both in vitro and in vivo. These scaffolds allow cells to attach and grow in a 3-dimensional space while nutrient flow is maintained throughout the matrix. The purpose of this study was to evaluate different biopolymer constructs and to determine mucosal engraftment rates and mucosal morphology.

Orthotopic transplantation of intestinal mucosal organoids in rodents.

Background: Orthotopic transplantation of intestinal mucosal organoids that contain putative mucosal stem cells serves as an important step toward implementing intestinal gene therapy and treatment for malabsorption syndromes in animals and humans. We hypothesized that intestinal mucosal organoids can be transplanted along the axis of the small bowel giving rise to a neomucosa expressing proteins of its donor origin.

Methods: Epithelial organoids were harvested from neonatal mice or rat small intestine with the use of a combination of enzymatic digestion with dispase and collagenase, and gravity sedimentation.

Engraftment of mucosal stem cells into murine jejunum is dependent on optimal dose of cells.

Background: Transplantation of intestinal mucosal stem cells is an important step in the development of intestinal gene therapy and treatment of intestinal mucosal diseases. We hypothesized that engraftment rates increase proportionally with increasing doses of seeded stem cells and increasing jejunal débridment.

Materials And Methods: Intestinal mucosal organoids were harvested from neonatal mice carrying a green-fluorescent protein (GFP) transgene and transplanted into adult GFP(-) mice (n = 66).

Treatment of bile acid malabsorption using ileal stem cell transplantation.

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.

Identification of optimal harvest sites of ileal stem cells for treatment of bile acid malabsorption in a dog model.

Ileal mucosal stem cells expressing the sodium-dependent ileal bile acid transporter (IBAT) have been successfully transplanted into the jejunum of rodents in projects aimed at creating a "neoileum" to treat bile acid malabsorption. To find optimal harvest sites for a dog model of stem cell transplantation, the exact location of peak IBAT expression in the donor ileum needs to be known. We therefore mapped IBAT function, IBAT mRNA, and IBAT protein in the ileum of Beagle dogs (N=3).