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Embryonic stem (ES) cells are capable of generating all cell types and tissues of the body. As such they represent an attractive source for therapeutic approaches. However, transplanted cells may be rejected by the immune system. One way to address this problem is to generate patient-specific ES cells. This, however, requires the transformation of the genetic program of somatic cells back to that of an early embryonic state. The field of stem cell research and reprogramming is rapidly evolving. This article aims at providing background information to understand some of the most exciting recent developments. Subsequently, the different existing strategies of converting somatic cells into ES-like cells are reviewed and evaluated.

Hematopoietic organs such as bone marrow contain various stem and progenitor cells with a differentiation capability exceeding hematopoiesis, a process also referred to as plasticity. Stem cells in bone marrow are hematopoietic stem cells, mesenchymal stem cells, and multipotent progenitor cells. Several examples for the development of stem cells of hematopoietic organs into nonhematopoietic tissue open novel ways in regenerative medicine. Animal experiments showed generation of neuronal tissue, cardiomyocytes and functional hepatocytes in injured tissue from bone marrow stem cells. Interpreting these results one has to keep in mind that besides transdifferentiation also cell fusion or heterogeneous stem cell populations might contribute to tissue regeneration. First clinical studies on therapy with bone marrow stem cells in myocardial infarction or liver embolization showed promising results.

Central to the successful surgically treatment numerous liver diseases is the ability of the organ to regenerate. The understanding of the process of self-renewal has both changed and progressed over the last few decades. For many years, the assumption was that the liver regenerates primarily through the division of mature liver cells. However, over the last few years there has been increasing evidence of the participation of stem cells. Intrahepatic stem cells, so-called oval cells, are activated under conditions of severe or chronic liver disease and originate from the canals of Hering. In addition, extrahepatic stem cells may migrate from the bone marrow into the liver when the regenerative capacity of the liver itself is depleted. It is not yet fully clear how the different stem cell populations interact with both each other and the mature liver cell population to achieve homeostatic cell and differentiation equilibrium in the diseased and/or regenerating organ. In any case, the outstanding growth potential of liver stem cells may become a clinically viable option in the field of cell transplantation.

Signal transfer between neurons and between neurons and muscle cells is mediated by the secretion of neurotransmitters. The axon of the presynaptic cell contains synaptic vesicles, the storage organelles for neurotransmitters. Arrival of an action potential causes calcium-influx into the axon and leads to fusion of synaptic vesicles with the presynaptic plasma membrane. Recently, the events between calcium-influx and membrane fusion were elucidated on a molecular level. The family of SNARE-proteins was identified as the key players in neurosecretion. They are located on synaptic vesicles (VAMP) or on the presynaptic plasma membrane (syntaxin, SNAP-25). Intimate protein-protein interactions between the SNARE-proteins are responsible for the attachment and merger of vesicle and the plasma membrane. Fusion is triggered by calcium-binding to synaptotagmin, another protein recently identified on synaptic vesicles. The molecular mechanism of the action of clostridial neurotoxins was also elucidated. Botulinum-as well as Tetanus toxins are proteases which cleave neuronal SNARE-proteins. This explains the long known inhibition of neurosecretion caused by these toxins. The proteolytic action of Tetanus- and Botulinum toxin occurs in different types of neurons, resulting in a stimulatory or inhibitory effect on muscle cells. This selective degradation of SNAREs explains the opposing clinical signs of tetanus (cramps) and botulismus (paralysis).

By December 1988 reports on 525 ARC- (AIDS-Related Complex) and AIDS-patients with neurological or neuropsychological signs treated with Zidovudine (AZT = 3'-Azido-2,3'Dideoxythymidine) had been published in literature. In 204 (38.8%) cases of HIV infection a temporary improvement in the neurological deficits was reported. Peripheral and central neurological side-effects were observed in 124 (23.6%) patients.

Defective hormone receptors are cultivated in cell cultures and subsequently reconstituted by, in-vitro cell fusion technique.

The development of cell polymorphy in human corneal endothelium was investigated by vital staining. Endothelial cell coalescence, cell loss and amitotic nucleus division are possible causes of endothelial cell polymorphy. These possible causes are differentiated by various temporary stages, the number of nuclei in polymorphous cells, their relation to the number of adjacent cells and their different sizes.

The secondary hard palate is formed by fusion of the right and left palatal shelves. During this process the cells of the medial edge epithelium (MEE) undergo autolysis. The present study, carried out on golden hamsters demonstrates that the glycogen content and the activities of phosphorylase, lactate-dehydrogenase (LDH), and succinic dehydrogenase (SDH) increase in the MEE-cells when the palatal shelves contact. These histochemical characteristics persist during the phase of degeneration of MEE. Thus, the increased glycogen content of the degenerating cells cannot be explained by a decrease of activity of these enzymes.

The cytogenesis of giant osteoclasts in Paget's disease of bone was studied by means of electron microscopy. 26 iliac crest biopsies were made and divided for light and electron microscopic investigation. A special procedure was used for electron microscopic preparation of bone without previous decalcification. Paget osteoclasts are characterized by their high content of nuclei. Several nuclei may show paracrystalline inclusions pointing to a possible virus infection of these cells. Giant osteoclasts have an increased mobility and a high resorptive activity, manifest by the dissection of bone fragments from endosteal bone surfaces. Cell membrane interdigitations between mononuclear cells and osteoclasts occur as a morphologic concomitant of cell fusion. Frequent occurence of such cell membrane contacts seem to indicate an increased tendency to cell fusion among the mononuclear precursors of Paget-osteoclasts. Precursor cells are located in the pericapillary region, and morphologically resemble pericytes. The assumption of an increased rate of cell fusion amoungst the precursor cells of osteoclasts might explain the development of giant osteoclasts in this disease. Further studies of the paracrystalline nuclear inclusions of Paget-osteoclasts are necessary to determine whether this process can be considered to be a cytopathogenic effect of virus infection.

During treatment of keratinizing squamous cell carcinomas with bleomycin tumor cells are devitalized by keratinization, while simple necrosis plays a minor role. Connected with this process is a marked resorptive granulomatous inflammation with numerous macrophages which is followed by a fibrous organization. In the border region of the keratinized tumor areas many multinucleated giant cells appear. The nature of these giant cells was the subject of controversy. Enzyme histochemical, electronmicroscopic, and ultrahistochemical investigations in three cases of advanced squamous cell carcinoma of the oral cavity prove that the giant cells which are formed during bleomycin treatment are not multinucleated tumor cells, but multinucleated macrophages. The enzymatic pattern is similar to macrophages with a high content of acid phosphatase and aminopeptidase. The ultrastructure of the giant cells is characterized by lysosomes with acid phosphatase activity, pinocytotic vesicles, and cytoplasmic projections on the cell surface with signs of macroendocytosis. The tumor cells show an epithelial differentiation with desmosomes, tonofibrils, and keratohyaline granula. The giant cells are formed by fusion of mononucleated (monocytogenic) macrophages. The fusions seem to be related to the functional status of the cells. It is possible, that the macrophages and the giant cells have an additional immunologic function. This is suggested by the frequent association of giant cells with lymphocytes. The importance of these facts for the evaluation of the action of bleomycin and the consequences for its therapeutic use are discussed. A combination with methods causing a dedifferentiation of the tumor or suppression of the immunologic defense seems to be problematic.

Following the presentation of some theories of cancer etiology the significance of the cell membrane in neoplastic transformation is stressed. Alterations of the cell surface are blamed responsible for the abnormal proliferative behaviour and metastasis of cancer cells. In addition, the disturbance of membrane-bound receptor structures might result in defects of "endocrine" control mechanisms leading to the typical uncontrolled growth of tumor cells. In this context, the membrane-bound adenylate-cyclase system deserves special interest, since hormone impulses stimulate this enzyme via specific receptors to produce cyclic AMP. This nucleotide transmits hormonal signals within the cell. Our own studies on lymphoma and leukemic cells are mentioned because they demonstrate alterations of the cAMP producing system in malignant cells. Finally, the phenomenon of cell fusion is discussed. Recently great attention has been paid to this technique, since hybridization experiments enable us to get new insight into the process of neoplastic transformation.

Until now numerous studies on central giant cell granuloma of jawbones have not been able to reveal the histogenesis of this tumourlike lesion. The aim of the present investigation in two surgically proven cases was to study this question by means of histochemical and electron-microscopic methods. Rather similar histochemical properties were shown in giant cells and pericytes of capillary sproute penetrating the granuloma. Cell fusion occurred between both cell types as was observed by electron microscopy. The process of cell fusion is defined by characteristic interdigitations of cell membranes. Therefore pericytes are believed to be the stem cells of multinucleated giant cells in giant cell granuloma. The abundance of giant cells usually occurring in the granuloma might be explained by plenty of capillary sprouts made up by clusters of pericytes. The factors inducing the pericytic cell fusion process are still unknown. The question arises whether cytogenesis of giant cells in giant cell granuloma might be similar in other giant cell lesions or even in the development of multinucleated osteoclasts.

Mouse monoclonal antibodies have been produced by fusion of x 63 Ag 8 . 653 myeloma cells with spleen cells of mice immunized with single cell suspensions of human mammary carcinoma tissue. These antibodies revealed strong differences in binding to cells from malignant and non malignant mammary tissues. The monoclonal antibodies do not react with usual determinants which are present on normal human blood lymphocytes or in human serum.