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To investigate functions of the homeodomain-containing transcription factor Nkx3.1 a null mutation was generated by targeted gene disruption introducing the bacterial LacZ gene as reporter into the locus. In addition to defects in duct morphogenesis of the prostate and bulbourethral gland displaying progressive epithelial hyperplasia and reduced ductal(More)
AIMS We explored the use of highly purified murine and human pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) to generate functional bioartificial cardiac tissue (BCT) and investigated the role of fibroblasts, ascorbic acid (AA), and mechanical stimuli on tissue formation, maturation, and functionality. METHODS AND RESULTS Murine and human(More)
Exploiting embryonic stem cell (ESC)-derived cardiomyocytes as a vital source for cell therapies and tissue engineering will depend on robust, large-scale production processes. Recently, we have reported stirring-controlled formation of embryoid bodies, enabling the generation of pure cardiomyocytes in 2-L scale. Expansion and differentiation of genetically(More)
To harness the potential of human pluripotent stem cells (hPSCs), an abundant supply of their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen was scaled up to stirred Erlenmeyer flasks and subsequently(More)
A practical synthesis of the Rho-Kinase inhibitor Y-27632 and two new fluoro derivatives was achieved in seven steps and with a good overall yield of 45% starting from commercially available (R)-1-phenylethylamine. Compared to Y-27632 the new fluoro derivatives showed reduced or no effect on hPSC vitality and expansion after dissociation in human(More)
BACKGROUND The limited effectiveness of cardiac cell therapy has generated concern regarding its clinical relevance. Experimental studies show that cell retention and engraftment are low after injection into ischemic myocardium, which may restrict therapy effectiveness significantly. Surgical aspects and mechanical loss are suspected to be the main culprits(More)
Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca2+-activated potassium channels (SKs 1-4).(More)
In vitro differentiation of human pluripotent stem cells (hPSCs) recapitulates early aspects of human embryogenesis, but the underlying processes are poorly understood and controlled. Here we show that modulating the bulk cell density (BCD: cell number per culture volume) deterministically alters anteroposterior patterning of primitive streak (PS)-like(More)
Overview: In driving hES cell technology towards widespread applications considerable effort has been focused on the improvement of culture conditions and on enabling efficient differentiation. We have established two technologies which will better enable researchers to achieve these aims. The use of feeder based protocols for the creation, expansion and(More)
Heart and vascular endothelial cells from human pluripotent stem cells are of interest for applications in cell therapy and cardiovascular disease. Differentiation protocols are now sufficiently refined that production of cardiomyocytes, endothelial-and smooth muscle cells is fairly efficient and reproducible. Genetically marked hESCs have been produced in(More)
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