Mesenchymatous Cells Research Articles

Pathogenesis of hyperostosis: A key role for mesenchymatous cells?

The similarities between diffuse idiopathic skeletal hyperostosis (DISH) and some forms of ankylosing spondylitis suggest shared pathogenic mechanisms. Entheseal ossification progresses at the same rate in the two conditions, and spondyloarthritis was the first diagnosis considered in several families with genetically determined early-onset DISH. However, DISH may be a heterogeneous condition, as the presence of peripheral calcifications in some families suggests pathogenic similarities with several animal models combining entheseal ossification and peripheral calcifications, as well as with X-linked familial hypophosphatemia and dentin-matrix-protein mutations. In the far more common presentation of hyperostosis without calcifications, entheseal ossification may be related to abnormal osteoblastic differentiation of mesenchymatous stem cells normally found around the intervertebral disks, in the vertebral periosteum, and in the anterior and posterior longitudinal ligaments. The many factors suspected of promoting this abnormal differentiation include bone morphogenetic proteins (BMPs), retinoids, and various hormonal factors; in addition, adipokines such as leptin are the focus of growing interest based on the well-documented association between DISH and obesity. Confirmation of the role for mesenchymatous cells in DISH should encourage investigations of mesenchymatous cells as possible pathogenic contributors to the entheseal abnormalities seen in spondyloarthritis. These cells normally exert immunosuppressive effects, which may be subverted in spondyloarthritis, notably by a T-cell population that homes specifically to the entheses.

The steroidogenic factor-1 protein is not expressed in various forms of endometriosis but is strongly present in ovarian cortical or medullary mesenchymatous cells adjacent to endometriotic foci

Steroidogenic factor-1 (SF-1) protein expression was not observed in any form of endometriosis (peritoneal, ovarian, or deep infiltrating endometriosis), which suggests that SF-1 locally produced by endometrial or stromal cells may not play a major role in the development of endometriosis. However, the strong expression of SF-1 in cortical and medullary ovarian mesenchymatous cells may be capable of creating a favorable steroidogenic environment and the development of the disease.

Steroidogenic Factor-1 Expression in Ovarian Endometriosis

Steroidogenic factor-1 (SF-1), a major protein regulating the complex cascade of steroidogenis, has been postulated to play a role in ovarian endometriosis. However, the expression in situ of SF-1 in ovarian endometriosis is unknown. To shed light on its presence, the expression of SF-1 was studied by immunohistochemistry in 30 cases of ovarian endometriosis (proliferative, n=15; secretory phase, n=15) and in 10 cases of normal eutopic endometrium coming from the same patients. No SF-1 immunoreactivity was observed in glands or endometrial stroma from ovarian endometriosis or eutopic endometrium. In contrast, a strong immunoreactivity was observed in the adjacent ovarian cortical or medullary mesenchymatous cells in all the cases examined independently of the cycle's phases. Contrary to the earlier reported hypothesis, our data showed for the first time the absence of SF-1 expression in glands and endometrial stroma from ovarian endometriosis and eutopic endometrium. However, the strong expression of SF-1 observed in cortical and medullary ovarian mesenchymatous cells adjacent to endometriosis, suggests a potential role for these cells in locally induced steroidogenesis.

Inventaire des stratégies cellulaires en ingénierie tissulaire de reconstruction osseuse

The objective of bone tissue engineering is to reconstruct bone stock using matrix structures, osteoinductor factors and osteogenic cells. Different types of natural or synthetic biomaterials are available or under development. The objective of recent work is to optimize matrix materials, particularly with better cell adhesion to the surface and better osteoconduction. For osteoinductors, most research is currently focused on bone morphogenetic protein (BMP) and angiogenic factors such as vascular endothelial growth factor (VEGF). Concerning the nature of the cells to be implanted, there is a clear dissociation between fundamental and clinical studies. Many clinical studies have demonstrated the strong osteogenic potential of fresh harvested total bone marrow. There has been nevertheless little fundamental work on the use of total bone marrow as a source of cells for bone tissue engineering. Most of the fundamental work has been focused on the use of mesenchymatous stromal cells selected from bone marrow and cultivated ex vivo. This approach which was first developed more than fifteen years ago has shown that the adjunction of these cells can improve the osteoformative capacity of bone substitutes. This strategy has, however, had almost no clinical impact to date since only two studies involving four patients have been reported. The purpose of this article is to review current research concerning bone tissue engineering using total bone marrow and mesenchymatous stromal cells.

Embryology of the internal carotid artery dural crossing: apropos of a continuous series of 48 specimens

The aim of this study was to describe the embryologic and foetal development of the anterior paraclinoid region and more precisely the relationship of the internal carotid artery to the dura mater. This has been done by examining a collection of histological sections, representing a continuous series of 48 embryologic and foetal specimens, covering the period of the first 6 months of intra-uterine life. Neurological and vascular elements develop during the embryologic period; the internal carotid artery is recognizable in the various sections of its course and acquires a histological adult parietal constitution. The foetal period corresponds to the development of the meningeal structures. The superior, medial and lateral walls appear on the fifteenth week of amenorrhoea and do not change after that. The internal carotid artery enters subarachnoid space accompanied by a sleeve of mesenchymatous cells, which fixes it to the anterior clinoid process. The constitution of this sleeve, arising from the superior wall of the lateral sellar compartment, remained independent of the principle vascular part, which allows the formation of a plan of cleavage. The foetal relations of the dura mater and the internal carotid artery were seen to be different from those of adult subjects described in the literature, suggesting an existence of period of maturation postnatally.

Tumeurs hépatiques malignes primitives en dehors du carcinome hépatocellulaire

Malignant primary tumours other than hepatocellular carcinoma are rare. They represent 2% to 3% of the gastrointestinal tract tumours. Unlike hepatocellular carcinoma, they develop most of the time in a non cirrhotic liver. These tumours may derive from the hepatocyte, cholangiocyte, mesenchymatous cells, or endocrine cells. Despite the fact that clinical and imaging features may suggest the nature of the tumour, the final diagnosis is based on the histopathologic examination of a liver biopsy or a surgical fragment.

豚の巣状分節性腎異形成症の1例

The color of the renal lobe of one kidney in a slaughtered pig had faded, and its cortex and medulla were thin. In histological terms, primitive tubules surrounded by a loose mesenchymatous stroma and scattered immature glomeruli were found in the lesion. Immature mesenchymatous cells had proliferated in the stroma. These morphological features led to a diagnosis of porcine focal segmental renal dysplasia.

Expression of the c-ets 1 gene in the hypothalamus and pituitary during rat development

The Ets gene family codes for transcription factors containing a conserved DNA binding domain. The proto-oncogene c-ets1 is highly expressed in lymphoid organs and in developing mesodermal-originating structures. We studied c-ets1 gene expression in the developing rat hypothalamo-hypophyseal system, using in situ hybridization on paraformaldehyde-fixed frozen sections. At embryonic day 12 (E12) and E13, cells synthesizing c-ets1 mRNA are found in the neural tube where they form small, heavily labeled strand-like and punctate structures; positive mesenchymatous cells, corresponding to the surface capillary network, surround the brain and hypophysis. C-ets1 mRNA is synthesized from E14 in the neural pituitary and E15 in the adenohypophysis, during angiogenesis; no c-ets1 mRNA is detected in the avascular intermediate pituitary at any stage. Strand-like c-ets 1 mRNA labeling is intense from E14 to E21 in the diencephalon. This labeling is also detected during perinatal stages in the hypothalamic magnocellular nuclei, one of the most richly vascularized brain areas. In the rat hypothalamo-hypophyseal system, c-ets1 gene expression is maximal during fetal and perinatal stages and progressively decreases thereafter until adulthood. The spatio-temporal correlation observed between c-ets1 gene expression and blood vessel formation in the rat hypothalamus and pituitary suggests a role for c-ets 1 in angiogenesis in this system.

Abnormal Development of the Os Penis in Male Mice Treated Neonatally with Tamoxifen

The os penis of male C57BL/Tw mice given 5 daily injections of 100 micrograms tamoxifen (Tx) starting on the day of birth (day 0) was examined at ages of 5-60 days; the bones of males given Tx injections for 5 days starting at 0-10 days and of those given neonatal injections of 100 micrograms clomiphene or nafoxidine were examined at 60 days. In the control males given the vehicle alone, the proximal segment of the os penis, composed of a compact cell mass found at day 0, developed at 5 days into the membrane bone with bone marrow and hyaline cartilage; the distal segment, composed of mesenchymatous cells until 10 days, developed at 30 days into fibrocartilage characterized by a distribution of type I collagen. By contrast, in Tx mice, fibrocartilage in the distal segment, and hyaline cartilage characterized by a distribution of type II collagen, and bone marrow in the proximal segment disappeared by 30 days. The maximum area of the proximal and distal segments gradually increased with age in control mice, whereas the proximal segment area remained unchanged in Tx mice. In clomiphene and nafoxidine mice at 60 days, the proximal segment was composed of hyaline cartilage; however, the distal segment lacked fibrocartilage. Hyaline cartilage in the proximal segment and fibrocartilage in the distal segment disappeared in all 60-day-old mice given Tx starting within 5 days. Neonatal castration did not suppress the formation of bone marrow and fibrocartilage in the os penis, though the bone size was smaller than in the intact controls. Formation of spines on the glans penis skin was suppressed by Tx given within 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain tissue and neural graft reactivity to the implantation of in situ self-assembled collagen matrices

The extracellular matrices of living tissue provide scaffolding supports for cell migration and interaction during tissue remodelling and regeneration and therefore may also be relevant to processes of regeneration in the injured central nervous system. We implanted in artificially made cavities of the neostriatum or cortex of adult rats a fluid collagen gelling system into which fetal grafts from either the substantia nigra or cortex were introduced. The collagen polymerizes to form a fibrillar matrix (organogel) which restitutes a physical continuity to the neural tissue. The host tissue reaction consisted of the ingrowth of blood vessels, the migration of mesenchymatous cells, of reactive astrocytes and of microglia within the bioimplant which became the substrate of heterogeneous cell interactions. As a result, newly formed collagen and carbohydrate-rich materials were deposited upon the collagen matrix while the bioimplant underwent remodelling. After 2 months, the original matrix was replaced by a glial-mesenchymal matrix into which nerve fibers of the lesioned striatum regenerated. The neural transplants survived and differentiated according to the stability of collagen matrices. We conclude that a collagen gelling system can be used to introduce a scaffolding structure into open brain wounds, and suggest that instead of sealing off the lesion, the ensuing scarring process rather favors tissue repair by establishing a glial-mesenchymal matrix well-suited for inducing intrinsic and extrinsic (grafts) neural regeneration.

Influences of weather on reproduction

The Ets gene family codes for transcription factors containing a conserved DNA binding domain. The proto-oncogene c-ets1 is highly expressed in lymphoid organs and in developing mesodermal-originating structures. We studied c-ets1 gene expression in the developing rat hypothalamo-hypophyseal system, using in situ hybridization on paraformaldehyde-fixed frozen sections. At embryonic day 12 (E12) and E13, cells synthesizing c-ets1 mRNA are found in the neural tube where they form small, heavily labeled strand-like and punctate structures; positive mesenchymatous cells, corresponding to the surface capillary network, surround the brain and hypophysis. C-ets1 mRNA is synthesized from E14 in the neural pituitary and E15 in the adenohypophysis, during angiogenesis; no c-ets1 mRNA is detected in the avascular intermediate pituitary at any stage. Strand-like c-ets 1 mRNA labeling is intense from E14 to E21 in the diencephalon. This labeling is also detected during perinatal stages in the hypothalamic magnocellular nuclei, one of the most richly vascularized brain areas. In the rat hypothalamo-hypophyseal system, c-ets1 gene expression is maximal during fetal and perinatal stages and progressively decreases thereafter until adulthood. The spatio-temporal correlation observed between c-ets1 gene expression and blood vessel formation in the rat hypothalamus and pituitary suggests a role for c-ets 1 in angiogenesis in this system.

Cartilage and bone formation in arterial wall. 2. Ultrastructural patterns.

The ultrastructural aspects of cartilaginous and osseous foci developed in aorta of rabbits immunized against rat aorta homogenates was studied. Besides normal and modified smooth muscle cells, various types of transformed mediacytes were observed in and around these foci: some of them resembled connective and young mesenchymatous cells, others had the appearances of cartilaginous and osseous cells. The possible role of the modified (multipotential) smooth muscle cells in aortic chondro- and osteogenesis is considered in some cases. Following histogenetic pathway is suggested: s.m.c. leads to modified s.m.c. lead to young mesenchyme-like cells ("inducible osteogenic precursor cells") leads to "chondro-mediacytes", "osteomediacyte".

Nerve dependent macromolecular synthesis in the epidermis and blastema of the adult newt regenerate.

The present study is an analysis of neurotrophic control of DNA and protein synthesis in the separated epidermis and blastema of the early newt limb regenerate. Previous macromolecular studies employed the entire regenerate without discrimination between its two components. The results demonstrate that the specific activities of newly synthesized protein and DNA show a nerve dependence in both epidermis and blastema. There appears to be a postdenervation rise in synthesis followed by a decline to a plateau level in both components, similar to what is reported for the whole regenerate. After two days of denervation DNA synthesis in the mesenchymatous cells is more profoundly depressed, suggesting that the epidermis is less nerve dependent.

Morphogenesis and ultrastructure of the mouse embryonic salivary gland in tissue culture. Normal, and following exposure to trypsin.

The primordial submandibular glands of 12-day-old mouse embryos were studied in tissue culture before and after treatment with trypsin under the electron microscope. In vitro differentiation proceeded normally and reached a high level of differentiation. Following a soak in trypsin for 15 or 30 minutes, considerable changes were noted in the basal lamina and in the mesenchymatous cells. There often occurred bizarre bullous protrusions of the cytoplasm through the apparently weakened basal lamina and the mesenchymatous cells were converted into so-called "ropalocytes". Subsequently the cells regained their normal appearance and the basement lamina was covered by a thick layer of amorphous electron-opaque basement membrane like material. It is concluded that the basal lamina (the basement membrane under the light microscope) might be the keystone in the differentiation of an organ and its maintenance in the adult. The development of innervation has also been studied and it was shown that the developing submandibular galnd is endowed with large bundles of nerve axons surrounded by Schwann cells lying in the epithelial-mesenchymal region. Intra-epithelial nerves were conspicuous and occasional synaptic bars or rings could be seen contributing to thedifferentiation of the secretory cell.

Mise en évidence du rôle, dans la régénération des Amphibiens, d’une glycoprotéine sécrétée par la cape apicale: étude cytochimique et autoradiographique en microscopie électronique

ABSTRACT Evidence for the role of an apical cap glycoprotein in amphibian regeneration : cytochemical and autoradiographic electron-microscopic studies Early during limb regeneration in the newt, an ectodermal apical cap covering a mesodermal blastema is formed. High-resolution autoradiography of these tissues has been carried out after incorporation of [3H]fucose, which is a precursor of glycoproteins. Autoradiography shows that silver particles are located at first on epithelial cells, then on mesenchymatous cells. This observation is consistent with a hypothesis in which the apical cap would elaborate a glycoprotein acting on the blastema. Substructural autoradiography and cytochemistry also show the importance of cellular surfaces for both cells producing glycoprotein and those which are target cells.

Origin and differentiative capacities of cells in the blastema of the regenerating salamander limb.

Synopsis. The salamander limb regenerate develops from a mesenchymatous bud of cells called the blastema. This review briefly considers the local origin and major features of blastemal cells and then discusses their role in the histogenesis of the regenerate. The capacity of blastemal cells to form the various cell types of the regenerate is first considered in general terms, with the discussion focusing on three major alternatives: blastemal cells form (a) cartilage only, (b) connective tissues only, or (c) essentially all internal tissues of the regenerate. The differentiative properties of blastemal cells originating from known cell types are then considered in detail. Cartilage is of particular interest in this regard, because it has been utilized as a pure cell type. Results from the study of mixed tissues, including muscle and connective tissue of the fin, are also presented. Information gained from the study of known cell types participating in regeneration is discussed in terms of the mechanisms responsible for the stability of cellular differentiation and in terms of the flow of cells from stump tissues into the regenerate. A bud of mesenchymatous cells, the blas? tema, forms at the distal end of the stump early in the regeneration of a salamander's limb. As these blastemal cells proliferate, the blastema elongates along the long axis of the limb, and the limb parts distal to the plane of amputation are replaced by the differentiation of the cells in the blas? tema. A detailed knowledge of both the origin and the differentiative capacities of the cells in the blastema is of central im? portance to an understanding of the pro? cess of regeneration. This knowledge is also important for our understanding of cell differentiation, especially the mechan? isms responsible for the stability of the differentiated state. This article is a brief review of cellular participation in limb re? generation, and it includes a preliminary report of the participation of tail-fin con? nective tissue cells in limb regeneration. Cytological aspects of regeneration have been reviewed in some detail by Hay (1962) as well as by Schmidt (1968), and more gen? eral aspects of regeneration have been reThis paper was written during the author's tenure as a post-doctoral fellow of The Muscular Dystrophy Associations of America, Inc.

Disposition of nerve fibers in the regenerating limb of the adult newt, Triturus.

AbstractBundles of nerve fibers invade the early regenerating limb of the adult newt Triturus. These fibers are unmyelinated and are only partly enveloped by accompanying Schwann cells. Isolated fibers make intimate contact with mesenchymatous cells. The fine structure of such contact regions suggests possible functional nerve terminations.

Eccentric blastema formation in aneurogenic limbs of Ambystoma larvae following epidermal cap deviation

The influence of the epidermal cap on blastema cell aggregation was studied by utilizing eccentric epidermal caps on aneurogenic and sparsely innervated forelimbs of Ambystoma larvae. When the position of an epidermal cap was shifted from its usual location to an eccentric one, mesenchymatous cells aggregated under it to establish a correspondingly eccentric blastema. Since the epidermal cap's influence on blastema cell aggregation was independent of the presence of nerves, these experiments lend further support to the hypothesis that, under the conditions of the present experiments, the epidermal cap of the regenerating limb functions to control the aggregation of the blastema cells.

The fine structure of mesenchymatous cells in the regenerating forelimb of the adult newt Triturus

The mesenchymatous cells in the regenerating forelimb of the adult newt were examined with the electron microscope. Most of the cells have an obvious and voluminous rough-surfaced endoplasmic reticulum occurring as numerous elongated strands, as small and large vesicles, or as irregularly shaped dilations; in a small number of cells the reticulum is sparse. In general, the cells have large ovoid nuclei, occasional prominent nucleoli, and distinct double nuclear envelopes with pores. The outer membrane of the envelope makes frequent incursions into the cytoplasm to merge with elements of the endoplasmic reticulum. There are numerous lipid droplets of various sizes within the cytoplasm. The fine structure of the cells of the adult regenerate is compared with that of the larva, and the possible significance of the differences in terms of the developmental capacities of the cells is discussed.

The acetylcholine content of the normal forelimb regenerate of the adult newt, Triturus

The acetylcholine content of normal and regenerating tissues of the forelimb of the newt was assayed by means of the clam heart. The results show that during the formative phases, during growth, and during differentiation there is a substantial amount of acetylcholine present in the regenerate. Indeed, the results suggest that within a few days of amputation, before the time of first appearance of mesenchymatous cells, the amount of acetylcholine probably resembles that of normal tissue. The studies also show that during the time when the nerve exerts its greatest influence upon growth, the acetylcholine content rises to a level high above that of normal tissue. Then, as differentiation sets in, it drops and eventually reaches the level of normal tissue. The significance of these variations is discussed in terms of the role of the nerve in regeneration of the limb; and the content of acetylcholine in the regenerate and embryo is compared.