Biomedical subjects
Publications and source records attributed to D Kluth.
Tracheal agenesis is a rare congenital malformation. Up to now no surgical concept exists for a definitive correction. In this paper we describe our experiences with an own case and discuss the purpose and justification of temporary surgical measures.
Developmental disorders in the period of the differentiation of the primitive foregut leads to atresia of the esophagus with tracheoesophageal fistula. Most authors think that this differentiation is caused by lateral foregut folds, which fuse in midline, thus forming the tracheoesophageal septum. In order to gain information about this period of development, we studied the foregut region of chick embryos by scanning electron microscopy (SEM) and light microscopy. In our study no signs of lateral folds or fusing foregut wall components, which were forming a tracheoesophageal septum, were found. Our study suggests that the development of the esophagus and trachea is the result of a simple reduction of the size of the primitive foregut. The consequence for the understanding of the embryology of the foregut malformations is discussed.
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Interference with respiration, caused by stenosis of the trachea after an operation for oesophageal atresia, is described. The narrowing of the tracheal lumen through blood vessels is particularly mentioned. Tracheal stenoses through the truncus brachiocephalicus, which cause serious symptoms following operation on oesophageal atresia, have a particular part to play. The causes of this are discussed, the clinical picture and steps in diagnosis are laid out. One case of atypical oesophageal atresia with an extremely hypoplastic left lung showed, after union of the oesophagus segments, the classic picture of serious tracheal compression through the truncus brachiocephalicus. This was caused by displacement of the mediastinum, pushing the heart backwards and to the left. It was cured by fixing the aortic arch to the sternum at the level of origin of the truncus. More than 1 1/2 years after the operation, the child is still symptom-free.
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The origin of liver cells from distinct bone marrow stem cells, eg, hematopoietic stem cells or multipotent adult progenitor cells has been recently described using in vitro studies. Cell culture experiments revealed the key role of growth factors and the organ-specific environment for the induction of liver-specific genes. We investigated the in vitro potential of rat mesenchymal stem cells to differentiate into hepatocytic cells in cocultures with isolated rat liver cells. Rat mesenchymal stem cells (MSCs) propagated in culture, and transduced with green fluorescent protein (GFP) were cloned. Cells from selected clones were either cultured under liver-stimulating conditions, using serum free medium supplemented with HGF, EGF, SCF, and FGF-4 alone on fibronectin-coated surfaces, or cocultured with freshly isolated rat liver cells. Cocultured cells were harvested after two weeks and sorted into GFP-positive (GFP+) and GFP-negative (GFP-) cells. RT-PCR for liver specific markers CK-18 and albumin were performed on the different cell populations. After 2 weeks, the specified culture conditions led to the expression of albumin and CK-18 RNA in GFP-positive sorted MSCs from the cocultures, whereas MSCs cultured without liver cells did not express the studied genes. The results indicate, that when cocultured with liver cells MSCs from the bone marrow have the potential to differentiate toward hepatocytic cells in vitro. We conclude that MSC may possess an enhanced capacity to differentiate into functional liver cells. Additionally, environmental factors seem to be crucial for specific and directed differentiation.
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For the development of innovative cell-based liver directed therapies, e.g. liver tissue engineering, the use of stem cells might be very attractive to overcome the limitation of donor liver tissue. Liver specific differentiation of embryonic, fetal or adult stem cells is currently under investigation. Different types of fetal liver (stem) cells during development were identified, and their advantageous growth potential and bipotential differentiation capacity were shown. However, ethical and legal issues have to be addressed before using fetal cells. Use of adult stem cells is clinically established, e.g. transplantation of hematopoietic stem cells. Other bone marrow derived liver stem cells might be mesenchymal stem cells (MSC). However, the transdifferentiation potential is still in question due to the observation of cellular fusion in several in vivo experiments. In vitro experiments revealed a crucial role of the environment (e.g. growth factors and extracellular matrix) for specific differentiation of stem cells. Co-cultured liver cells also seemed to be important for hepatic gene expression of MSC. For successful liver cell transplantation, a novel approach of tissue engineering by orthotopic transplantation of gel-immobilized cells could be promising, providing optimal environment for the injected cells. Moreover, an orthotopic tissue engineering approach using bipotential stem cells could lead to a repopulation of the recipients liver with healthy liver and biliary cells, thus providing both hepatic functions and biliary excretion. Future studies have to investigate, which stem cell and environmental conditions would be most suitable for the use of stem cells for liver regeneration or tissue engineering approaches.
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