Differentiation and transdifferentiation of adrenal chromaffin cells of the guinea-pig. I. Transplants to the anterior chamber of the eye.
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Xenopus embryonic epidermis changes its cellular composition during development: the appearance of ciliated epidermal cells before hatching is a remarkable characteristic. In this study, the functional change of ciliated cells to mucus-secreting cells was examined with immunocytochemistry using anti-tubulin and anti-chondroitin 6-sulfate (C6S). Before hatching, most epidermal cells were labeled with anti-C6S in a granular fashion. Immunoelectron microscopy revealed that the anti-C6S-positive structure was the mucus granule. Ciliated epidermal cells lacked anti-C6S staining, but were strongly labeled with anti-tubulin. After hatching, most ciliated cells in the surface of the embryo disappeared. During their disappearance, some ciliated cells exhibited anti-C6S-positive granular labeling. This strongly suggests that the disappearance of ciliated cells is a functional conversion to mucus-secreting cells instead of shedding through cell death.
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By means of hybridization with DNA complementary to delta-crystallin mRNA (delta-mRNA) sequences (delta-cDNA), the levels of delta-mRNA in three different culture systems of 8-day-old chick embryonic neural retina were determined. After 30 days of culturing in vitro, the level of delta-mRNA in cells cultured under conditions of spreading cultures (SpC) was 50 times higher than in the cells maintained in aggregate cultures (AgC) throughout. When the cells pre-cultivated in SpC for an initial 10 days were transferred into AgC, the delta-mRNA level in 30-day cultures was 40 times higher than that in 3-day SpC. The level of delta-mRNA in neural retina in situ was negligible, but it became detectable in 10-day SpC. The initial appearance of detectable delta-mRNA in 10-day SpC coincides with the timing of 'transdetermination' of neural retina cells into lens cells.
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Liver injury induces activation of hepatic stellate cells (HSCs) comprising expression of receptors, proliferation, and extracellular matrix synthesis triggered by a network of cytokines provided by damaged hepatocytes, activated Kupffer cells and HSCs. While 6 days after bile duct ligation in rats TGF-beta inhibited DNA synthesis in HSCs, it was enhanced after 14 days, indicating a switch from suppression to DNA synthesis stimulation during fibrogenesis. To delineate mechanisms modulating TGF-beta function, we analyzed crosstalk with signaling pathways initiated by cytokines in damaged liver. Lipopolysaccharide and tumor necrosis factor-alpha enhanced proliferation inhibition of TGF-beta, whereas interleukin-6, oncostatin M, interleukin-1alpha, and interleukin-1beta did not. Hepatocyte growth factor (HGF) counteracted TGF-beta dependent inhibition of DNA synthesis in quiescent HSCs. Since expression of c-met is induced during activation of HSCs and HGF is overrepresented in damaged liver, crosstalk of HGF and TGF-beta contributes to loss of TGF-beta dependent inhibition of DNA synthesis in HSCs.
Recent findings indicate that adult BM contains cells that can differentiate into mature, nonhematopoietic cells of multiple tissues including cells of the kidney, lung, liver, skin and GI tract and fibers of heart and skeletal muscle. Recently the number of these observations has substantially increased, but there is a lack of information on the mechanistic issues in stem cell plasticity. In three different models for skin, liver and skeletal muscle plasticity, we have shown that following transplantation of the marrow cells from green fluorescent protein (GFP) transgenic mice, high levels of conversion of marrow cells can be identified. Injury to the tissue was the single most important factor for this phenomenon since the incidence of marrow to other tissue conversions significantly increased after tissue injury was implemented. Our studies also demonstrate the effect of radiation on the extent of marrow conversion.
We report the identification and isolation of limbal fibroblast-like cells from adult corneo-limbal tissue possessing self-renewing capacity and multilineage differentiation potential. The cells form cell aggregates or clusters, which express molecular markers, specific for ectoderm, mesoderm and endoderm lineages in vitro. Further, these cells mature into a myriad of cell types including neurons, corneal cells, osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes and pancreatic islet cells. Despite originating from a non-embryonic source, they express ESC and other stem cell markers important for maintaining an undifferentiated state. This multipotential capability, relatively easy isolation and high rate of ex vivo proliferation capacity make these cells a promising therapeutic tool.
Recent advances in pancreatic islet transplantation emphasize the potential of this approach for the long-term control of blood glucose levels in diabetic patients. However, tissue-replacement therapy will become widely available as a treatment for diabetes only when new sources of islets and insulin-producing cells are found. Here, we review recent evidence that documents the potential of mature liver as a source of tissue for generating a functional endocrine pancreas, by ectopic expression of pancreatic transcription and differentiation factors. When key events in the transconversion process have been identified, using the liver as a source of pancreatic tissue might provide a valuable approach for replacing impaired beta cell function in diabetics.
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