Culture of mouse embryonic stem cells with serum but without exogenous growth factors is sufficient to generate functional hepatocyte-like cells.

Mouse embryonic stem cells (mESC) have been used to study lineage specification in vitro, including towards a hepatocyte-like fate, and such investigations guided lineage differentiation protocols for human (h)ESC. We recently described a four-step protocol to induce hepatocyte-like cells from hESC which also induced hepatocyte-like cell differentiation of mouse induced pluripotent stem cells. As ESC also spontaneously generate hepatocyte-like cells, we here tested whether the growth factors and serum used in this protocol are required to commit mESC and hESC to hepatocyte-like cells.

Directed differentiation of murine-induced pluripotent stem cells to functional hepatocyte-like cells.

Background & Aims: Induced pluripotent stem (iPS) cells exert phenotypic and functional characteristics of embryonic stem cells even though the gene expression pattern is not completely identical. Therefore, it is important to develop procedures which are specifically oriented to induce iPS cell differentiation.

Methods: In this study, we describe the differentiation of mouse iPS cells to hepatocyte-like cells, following a directed differentiation procedure that mimics embryonic and fetal liver development.

Human embryonic and rat adult stem cells with primitive endoderm-like phenotype can be fated to definitive endoderm, and finally hepatocyte-like cells.

Stem cell-derived hepatocytes may be an alternative cell source to treat liver diseases or to be used for pharmacological purposes. We developed a protocol that mimics mammalian liver development, to differentiate cells with pluripotent characteristics to hepatocyte-like cells. The protocol supports the stepwise differentiation of human embryonic stem cells (ESC) to cells with characteristics of primitive streak (PS)/mesendoderm (ME)/definitive endoderm (DE), hepatoblasts, and finally cells with phenotypic and functional characteristics of hepatocytes.

Differentiation of rat multipotent adult progenitor cells to functional hepatocyte-like cells by mimicking embryonic liver development.

Differentiation of stem cells to hepatocytes has industrial applications, as well as the potential to develop new therapeutic strategies for liver disease. The protocol described here, sequentially using cytokines that are known to have a role in liver embryonic development, efficiently differentiates rat multipotent adult progenitor cells (rMAPCs) to hepatocyte-like cells by directing them through defined embryonic intermediates, namely, primitive streak/mesendoderm/definitive endoderm, hepatoblast and hepatocyte-like phenotype. After 20 days, the final differentiated multipotent adult progenitor cell progeny is a mixture of cells, comprising cells with the characteristics of hepatoblasts and a smaller cell fraction with the morphological and phenotypical features of mature hepatocytes, as well as other mesodermal cells and some persistent undifferentiated rMAPCs.

Isolation procedure and characterization of multipotent adult progenitor cells from rat bone marrow.

Multipotent adult progenitor cells (MAPCs) are adult stem cells derived from the bone marrow of mouse and rat and were described for the first time in 2002 (Jiang et al., Nature 418:41-49, 2002), and subsequently (Breyer et al., Exp Hematol 34:1596-1601, 2006; Jiang et al.

Cytomegalovirus-associated superior mesenteric vein thrombosis treated with systemic and in-situ thrombolysis.

A 56-year-old patient, first diagnosed with an acute cytomegalovirus infection, presented with progressive abdominal pain because of a superior mesenteric vein thrombosis for which he was treated with systemic thrombolysis and heparin in continuous infusion. As this therapy did not have the intended success after 5 days, an interventional radiological procedure was performed with local thrombolysis in the superior mesenteric artery resulting in recanalisation of the vein. Oral anticoagulation was initiated and continued for a period of 6 months.

Comparative transcriptome analysis of embryonic and adult stem cells with extended and limited differentiation capacity.

Background: Recently, several populations of postnatal stem cells, such as multipotent adult progenitor cells (MAPCs), have been described that have broader differentiation ability than classical adult stem cells. Here we compare the transcriptome of pluripotent embryonic stem cells (ESCs), MAPCs, and lineage-restricted mesenchymal stem cells (MSCs) to determine their relationship.

Results: Applying principal component analysis, non-negative matrix factorization and k-means clustering algorithms to the gene-expression data, we identified a unique gene-expression profile for MAPCs.

7. Transplantation of undifferentiated, bone marrow-derived stem cells.

Stem cell research has known an enormous development, and cellular transplantation holds great promise for regenerative medicine. However, some aspects, such as the mechanisms underlying stem cell plasticity (cell fusion vs true transdifferentiation) and the functional improvement after stem cell transplantation, are highly debated. Furthermore, the great variability in methodology used by several groups, sometimes leads to confusing, contradicting results.

Safety and efficacy of weekly docetaxel in frail and/or elderly patients with metastatic breast cancer: a phase II study.

This phase II study was designed to evaluate the safety and efficacy of weekly docetaxel (36 mg/m) for the treatment of metastatic breast cancer in 47 frail and/or elderly patients who were ineligible for the standard 3-weekly docetaxel (100 mg/m) regimen. Reasons for ineligibility to the latter were age > or = 70 years (10 patients), poor hematological reserves (15 patients), impaired liver function (eight patients), intolerance to previous taxanes administered 3-weekly without demonstrated resistance (five patients) or any combination of these reasons (nine patients). There was a median of two prior chemotherapy regimens and more than 60% had a WHO performance score at baseline of 2-3.