Osseous metaplasia in an ulcerating tubular adenoma of the colon: a case report

<p>Abstract</p> <p>Introduction</p> <p>Heterotopic bone is rarely found in the gastrointestinal tract. Here we report a rare case of metaplastic ossification within a benign ulcerating adenoma and review the literature concerning the aetiology.</p> <p>Case presentation</p> <p>A 63-year-old woman, who presented with a history of melaena, was found at colonoscopy to have a pedunculated ulcerating polyp. Histological examination demonstrated multiple areas of osseous metaplasia within the polyp stroma.</p> <p>Conclusion</p> <p>Heterotopic ossification in colonic adenomas is a particularly rare phenomenon, with the majority of cases occurring within malignant lesions. The suggested mechanisms for its aetiology still remain unclear.</p

Therapeutic Cell Repopulation of the Liver: From Fetal Rat Cells to Synthetic Human Tissues

Progenitor cells isolated from the fetal liver can provide a unique cell source to generate new healthy tissue mass. Almost 20 years ago, it was demonstrated that rat fetal liver cells repopulate the normal host liver environment via a mechanism akin to cell competition. Activin A, which is produced by hepatocytes, was identified as an important player during cell competition. Because of reduced activin receptor expression, highly proliferative fetal liver stem/progenitor cells are resistant to activin A and therefore exhibit a growth advantage compared to hepatocytes. As a result, transplanted fetal liver cells are capable of repopulating normal livers. Important for cell-based therapies, hepatic stem/progenitor cells containing repopulation potential can be separated from fetal hematopoietic cells using the cell surface marker δ-like 1 (Dlk-1). In livers with advanced fibrosis, fetal epithelial stem/progenitor cells differentiate into functional hepatic cells and out-compete injured endogenous hepatocytes, which cause anti-fibrotic effects. Although fetal liver cells efficiently repopulate the liver, they will likely not be used for human cell transplantation. Thus, utilizing the underlying mechanism of repopulation and developed methods to produce similar growth-advantaged cells in vitro, e.g., human induced pluripotent stem cells (iPSCs), this approach has great potential for developing novel cell-based therapies in patients with liver disease. The present review gives a brief overview of the classic cell transplantation models and various cell sources studied as donor cell candidates. The advantages of fetal liver-derived stem/progenitor cells are discussed, as well as the mechanism of liver repopulation. Moreover, this article reviews the potential of in vitro developed synthetic human fetal livers from iPSCs and their therapeutic benefits

Influence of chronic renal failure on protein synthesis and albumin metabolism in rat liver

Abstract. Previously we reported that chronic renal failure in rats leads to preferential disaggregation of liver membrane-bound polysomes associated with a decrease in albumin synthesis. To determine whether reduced albumin synthesis results from reduced cellular levels of albumin messenger RNA (mRNA) or some other molecular mechanism, we have employed mRNA-DNA hybridization in conjunction with cell-free protein synthesis to determine albumin mRNA sequence content and biological activity in subcellular fractions from control and uremic rat liver. Using high specific activity albumin [3H]-complementary DNA prepared from purified-albumin mRNA, we found that total liver polysomes and albumin mRNA sequence content are increased in uremic animals. The extra polysomes are located within the membrane-bound subcellular fraction. These polysomes, however, have reduced ability to synthesize albumin in the cell-free system, and mRNA isolated from membranebound polysomes ofuremic liver showed reduced albumin synthesis. Evaluation of albumin mRNA size by hybridization analysis revealed a reduced content of intact albumin mRNA molecules per microgram of RNA in the A preliminary report of this work has been previously published in abstract form in 1981, Hepatology

Massive Liver Replacement by Transplanted Hepatocytes in the Absence of Exogenous Growth Stimuli in Rats Treated with Retrorsine

A strategy for hepatocyte transplantation was recently developed whereby massive replacement of the recipient liver is achieved after a combined treatment with retrorsine, a pyrrolizidine alkaloid, and partial hepatectomy. We now investigated whether liver repopulation could occur in this animal model in the absence of any exogenous growth stimuli (eg, partial hepatectomy) for the transplanted cells. Dipeptidyl-peptidase type IV-deficient (DPPIV(−)) rats were used as recipients. Rats were given two injections of retrorsine (30 mg/kg each, 2 weeks apart), followed by transplantation of 2 × 10(6) hepatocytes isolated from a normal, syngeneic, DPPIV(+) donor. At 2 weeks after transplantation, clusters of DPPIV(+) hepatocytes occupied 3.3 ± 0.9% of host liver, increasing to 38.2 ± 6.3% at 2 months, and to 65.9 ± 8.8% at 5 months. By 1 year, >95% of the original hepatocytes were replaced by donor-derived cells. Serum parameters related both to hepatocyte function and integrity (including glucose, bilirubin, total proteins, cholinesterase, alanine aminotransferase, and alkaline phosphatase) were in the normal range in retrorsine-treated and repopulated animals. These results provide further insights toward developing strategies for effective liver repopulation by transplanted hepatocytes with reduced toxicity for the host and potential clinical applicability