Intussusceptive angiogenesis and its counterpart intussusceptive lymphangiogenesis.

Intussusceptive angiogenesis (IA) is currently considered an important alternative and complementary form of sprouting angiogenesis (SA). Conversely, intussusceptive lymphangiogenesis (IL) is in an initial phase of study. We compare their morphofunctional characteristics, since many can be shared by both processes. To that end, the following aspects are considered: A) The concept of IA and IL as the mechanism by which blood and lymphatic vessels split, expand and remodel through transluminal pillar formations (hallmarks of intussusception). B) Terminology and historical background, with particular reference to the group of Burri, including Djonov and Patan, who initiated and developed the vessel intussusceptive concept in blood vessels. C) Incidence in normal (e.g. in the sinuses of developing lymph nodes) and pathologic conditions, above all in vessel diseases, such as dilated veins in hemorrhoidal disease, intravascular papillary endothelial hyperplasia (IPEH), sinusoidal hemangioma, lobular capillary hemangioma, lymphangiomas/lymphatic malformations and vascular transformation of lymph nodes. D) Differences and complementarity between vessel sprouting and intussusception. E) Characteristics of the cover (endothelial cells) and core (connective tissue components) of pillars and requirements for pillar identification. F) Structures involved in pillar formation, including endothelial contacts of opposite vessel walls, interendothelial bridges, merged adjacent capillaries, vessel loops and spilt pillars. G) Structures resulting from pillars with intussusceptive microvascular growth, arborization, remodeling and segmentation (compartmentalization). H) Influence of intussusception in the morphogenesis of vessel tumors/ pseudotumors; and I) Hemodynamic and molecular control of vessel intussusception, including VEGF, PDGF BB, Hypoxia, Notch, Endoglobin and Nitric oxide.

Increase of germ cell nuclear factor expression in globozoospermic Gopc-/- knockout mice.

BACKGROUND: Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC) is a Golgi protein that plays a role in vesicular transport and intracellular protein trafficking and degradation. Mice deficient in GOPC protein have globozoospermia and are infertile. The germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily which is expressed in male germ cells, from spermatocytes and spermatids, both in the nucleus and the acrosomal region. It is not known if its expression could be altered in Gopc-/- mice with defective acrosomes. OBJECTIVES: The aim of the present work was to analyze the distribution of GCNF protein in spermatids of Gopc-/- knockout mice. MATERIALS AND METHODS: We have analyzed the expression and distribution during spermatogenesis of GCNF and its deregulation in Gopc-/- mutant mice by RT-qPCR, Western blot, immunohistochemistry and immunogold. RESULTS: Germ cell nuclear factor was localized in the nucleus of all the cell types in the seminiferous tubules. Despite being a nuclear protein, it was also located in the acrosome and in the manchette of elongating spermatids. We have found that in the absence of GOPC, the expression of GCNF was increased in the nucleus of spermatocytes, mainly in leptotene, and in the nucleus and the manchette during the spermatid elongation. DISCUSSION AND CONCLUSION: Gopc-/- mice have defective acrosome and manchette. The manchette is involved in the transport of proteins through the cytoplasm and the nucleus. Considering that the GCNF protein is normally transported to the acrosome and the nucleus, it can be thought that transport deficiencies in Gopc-/- mice are responsible for the increased expression of this protein.

Morphofunctional basis of the different types of angiogenesis and formation of postnatal angiogenesis-related secondary structures.

We review the morpho-functional basis of the different types of angiogenesis and report our observations, including the formation of angiogenesis-related secondary structures. First of all, we consider the following issues: a) conceptual differences between angiogenesis and vasculogenesis, b) incidence of angiogenesis in pre- and postnatal life, c) regions of vascular tree with angiogenic capacity, d) cells (endothelial cells, pericytes, CD34+ adventitial stromal cells of the microvasculature and inflammatory cells) and extracellular matrix components involved in angiogenesis, e) events associated with angiogenesis, f) different types of angiogenesis, including sprouting and intussusceptive angiogenesis, and other angiogenic or vascularization forms arising from endothelial precursor cells (postnatal vasculogenesis), vasculogenesis mimicry, vessel co-option and piecemeal angiogenesis. Subsequently, we consider the specific morpho-functional characteristics of each type of angiogenesis. In sprouting angiogenesis, we grouped the events in three phases: a) activation phase, which includes vasodilation and increased permeability, EC, pericyte and CD34+ adventitial stromal cell activation, and recruitment and activation of inflammatory cells, b) sprouting phase, encompassing EC migration (concept and characteristics of endothelial tip cells, tip cell selection, lateral inhibition, localized filopodia formation, basal lamina degradation and extracellular changes facilitating EC migration), EC proliferation (concept of endothelial stalk cells), pericyte mobilization, proliferation, recruitment and changes in CD34+ adventitial stromal cells and inflammatory cells, tubulogenesis, formation of a new basal lamina, and vascular anastomosis with capillary loop formation, and c) vascular remodelling and stabilization phase (concept of phalanx cells). Subsequently, the concept, incidence, events and mechanisms are considered in the other forms of angiogenesis. Finally, we contribute the formation of postnatal angiogenesis-related secondary structures: a) intravascular structures through piecemeal angiogenesis, including intravascular papillae in vessel tumours and pseudotumours (intravascular papillary endothelial hyperplasia, vascular transformation of the sinus in lymph nodes, papillary intralymphatic angioendothelioma or Dabska tumour, retiform hemangioendothelioma, hemangiosarcoma and lymphangiosarcoma), vascular septa in hemorrhoidal veins and intravascular projections in some tumours; b) arterial intimal thickening; c) intravascular tumours and pseudotumours (e.g. intravenous pyogenic granulomas and intravascular myopericytoma); d) vascular glomeruloid proliferations; and e) pseudopalisading necrosis in glioblastoma multiform.

Telocyte Behaviour During Inflammation, Repair and Tumour Stroma Formation.

In this chapter, we outline the role of human CD34+ stromal cells/telocytes (CD34+ SC/TCs) as progenitor cells during repair. The in vivo activation phenomena of CD34+ SC/TCs in this process include increased size; separation from the neighbouring structures (mainly of the vascular walls); association with inflammatory cells, predominantly macrophages; development of the organelles of synthesis (rough endoplasmic reticulum and Golgi apparatus); cell proliferation with presence of mitosis and high proliferative index (transit-amplifying cells); and fibroblastic and myofibroblastic differentiation. A procedure to study these tissue-resident cells, comparison of their behaviour in vivo and in vitro and different behaviour depending on location, time, type of injury (including tumour stroma) and greater or lesser proximity to the injury are also considered.

Intravascular papillary endothelial hyperplasia (IPEH). Evidence supporting a piecemeal mode of angiogenesis from vein endothelium, with vein wall neovascularization and papillary formation.

Intravascular papillary endothelial hyperplasia (IPEH) is a reactive process of questioned pathogenesis (primary proliferation of endothelial cells/ECs versus organizing thrombi). The aim of this study is to assess the organization of morphologic patterns, with precise location of neovascularization and papillary distribution in IPEH to clarify the role of the vein wall (mainly vein intimal ECs) in lesion development and papillary formation. We studied 12 cases of IPEH in skin and subcutaneous veins by serial histological sections and immunohistochemical procedures. In four well-structured cases (the remaining cases showed overlapping events), we found four principal histological patterns organized by zone: 1) invaginated vein wall zone with microvascular networks. The intraparietal microvessels presented CD34+ and CD31+ ECs arising from ECs of the vein intima, and αSMA+ pericyte-like cells originating from modified SMCs of the media layer. 2) Papillary zone, generally with myriad papillae, formed by ECs of intraparietal microvessel networks encircling vein wall components (parietal papillae). 3) Organizing thrombotic zone from microvascular networks of invaginated vein wall zone. 4) Unorganized thrombotic zone partially covered by ECs, also originating from vein intimal endothelium and arranged in a monolayer or encircling thrombotic fibrin (thrombotic papillae). In conclusion, the capacity of vein intimal ECs and those originating from them (in newly-formed microvessels in the vein itself and covering the unorganized thrombi) to encircle vein wall components or fibrin, and to form papillae (ECs form the cover and encircled components the core) supports a piecemeal mode of angiogenesis as a pathogenic basis of IPEH. This mechanism encompasses the two histogenetic hypotheses outlined above.

Changes in Testicular Interstitial Connective Tissue of Hamsters (Mesocricetus auratus) During Ageing and After Exposure to Short Photoperiod.

The testicular interstitium of Syrian hamster (Mesocricetus auratus) was studied during ageing and in testicular regression after exposure to a short photoperiod, in relation to the interstitial cells and their connective tissue. This tissue was assessed histochemically using Masson's trichrome technique and the expression of Heat Shock Protein 47 (HSP-47) and collagen IV (α5) was assessed in Leydig cells. Finally, an ultrastructural analysis of some cells of the testicular interstitium was made. Leydig cells were positive for HSP-47 and collagen IV (α5). Ageing did not change the parameters studied while the short photoperiod altered the synthetic activity of Leydig cells. The positivity index of these cells for HSP-47 was significantly higher in the regressed testis, but was lower for collagen IV (α5). During ageing no change were observed. Ultrastructural Leydig cells showed a discontinuous basal lamina that did not change during ageing. The basal lamina was not identified in Leydig cells regressed by exposure to a short photoperiod. In conclusion; the intertubular connective tissue suffers little change with age. By contrast, in the testis regressed after exposure to a short photoperiod the studied parameters related to the intertubular connective tissue were altered. These changes are probably related with the low synthetic activity of regressed Leydig cell.

Cellular changes in the hamster testicular interstitium with ageing and after exposure to short photoperiod.

The aim of this study was to evaluate the cellular changes that occur in the hamster testicular interstitium in two very different physiological situations involving testicular involution: ageing and exposure to a short photoperiod. The animals were divided into an 'age group' with three subgroups - young, adult and old animals - and a 'regressed group' with animals subjected to a short photoperiod. The testicular interstitium was characterised by light and electron microscopy. Interstitial cells were studied histochemically with regard to their proliferation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling (TUNEL+) and testosterone synthetic activity. We identified two types of Leydig cell: Type A cells showed a normal morphology, while Type B cells appeared necrotic. With ageing, pericyte proliferation decreased but there was no variation in the index of TUNEL-positive Leydig cells. In the regressed group, pericyte proliferation was greater and TUNEL-positive cells were not observed in the interstitium. The testicular interstitium suffered few ultrastructural changes during ageing and necrotic Leydig cells were observed. In contrast, an ultrastructural involution of Leydig cells with no necrosis was observed in the regressed group. In conclusion, the testicular interstitium of Mesocricetus auratus showed different cellular changes in the two groups (age and regressed), probably due to the irreversible nature of ageing and the reversible character of changes induced by short photoperiod.

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod.

During the non-breeding season some animals exhibit testicular atrophy, decreased testicular weight and reduced seminiferous tubule diameter accompanied by depletion of the seminiferous epithelium. Some cellular factors involved in this depletion are changes in germ cell proliferation and apoptosis. In the Syrian hamster this depletion has been studied histologically and in terms of the involvement of proliferation and apoptosis in the seminiferous epithelium of fully regressed testes. The objectives of this study included the histomorphometrical characterization of the testis and the determination of the proliferative and apoptotic activity of germ cells in the seminiferous epithelium during testicular regression owing to short photoperiod. The study was performed using conventional light microscopy (hematoxylin and eosin), proliferating cell nuclear antigen and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling staining, image analysis software, and transmission electron microscopy in three established regression groups: mild regression (MR), strong regression (SR), and total regression (TR). Morphometrically a gradual decrease in total tubular area and in the testicular, tubular, and epithelial volumes was observed during testicular regression. Interstitial and luminal volumes decreased from the MR group onwards. The tubular length decreased from MR to SR. As regards spermatogonial proliferation, only an initial decrease in proliferative activity was observed, whereas apoptotic germ cell activity increased throughout regression. The number of germ cells studied decreased throughout the process of testicular regression. In conclusion, testicular regression in Syrian hamster comprises two histomorphometrical phases, the first involving a decrease in seminiferous tubular diameter and volume and the second involving shortening of the seminiferous tubule and a decrease in interstitial volume. At the cellular level, there is an initial decrease in proliferation and increase in apoptosis involving all germ cells. At the end of regression, the proliferative and apoptotic activities of the spermatogonia recover the values observed prior to regression in preparation for recrudescence.

Human resident CD34+ stromal cells/telocytes have progenitor capacity and are a source of αSMA+ cells during repair.

We studied the progenitor capacity of human resident CD34+ stromal cells/telocytes (SC/TCs) in the enteric wall affected by inflammatory/repair processes (appendicitis, diverticulitis of large bowel and Crohn's disease of the terminal ileum) at different stages of evolution (inflammatory, proliferative and remodelling). In these conditions, CD34+ SC/TCs are activated, showing changes, which include the following overlapping events: 1) separation from adjacent structures (e.g., from vascular walls) and location in oedematous spaces, 2) morphological modifications (in cell shape and size) with presence of transitional cell forms between quiescent and activated CD34+ SC/TCs, 3) rapid proliferation and 4) loss of CD34 expression and gain of αSMA expression. These events mainly occur in the inflammatory and proliferative stages. During the loss of CD34 expression, the following findings are observed: a) irregular cell labelling intensity for anti-CD34, b) co-localization of CD34 and actin, c) concurrent irregular labelling intensity for αSMA and d) αSMA expression in all stromal cells, with total loss of CD34 expression. While CD34 expression was conserved, a high proliferative capacity (Ki-67 expression) was observed and vice versa. In the segments of the ileum affected by Crohn's disease, the stromal cells around fissures were αSMA+ and, in the transitional zones with normal enteric wall, activated CD34+ SC/TCs were observed. In conclusion, human resident CD34+ SC/TCs in the enteric wall have progenitor capacity and are activated with or without differentiation into αSMA+ stromal cells during inflammatory/repair processes.

CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology.

We review the morphofunctional characteristics of CD34+ stromal fibroblastic/fibrocytic cells (CD34+ SFCs) and report our observations. We consider the following aspects of CD34+ SFCs: A) The confusing terms applied to this cell type, often combining the prefix CD34 with numerous names, including fibroblasts, fibrocytes, dendrocytes, keratocytes, telocytes and stromal, dendritic, adventitial, supraadventitial, perivascular, paravascular and delimiting cells; B) Changes in their immunophenotype, e.g., loss of CD34 expression and gain of other markers, such as those defining mesenchymal and derivate cells (myofibroblasts, osteoblasts, chondroblasts, adipocytes); C) Morphology (elongated or triangular cell body and thin, moniliform, bipolar or multipolar cytoplasmic processes), immunohistochemistry (co-expression of and changes in molecular expression) and structure (characteristics of nucleus and cytoplasmic organelles, and points of contact and junctions in quiescent and activated stages by light and electron microscopy); D) Location and distribution in the vessels (adventitia or external layer), in the tissues (connective, adipose, blood, muscle and nervous) and in the organs and systems (skin, oral cavity and oropharynx, respiratory, digestive, urinary, male, female, endocrine and lymphoid systems, serosal and synovial membranes, heart, eye and meninges); E) Origin from the mesoderm and cranial neural crest in the embryo, and from stem cells (themselves or other cells) and/or peripheral blood pluripotent stem cells (circulating progenitor cells) in post-natal life; F) Functions, such as synthesis of different molecules, progenitor of mesenchymal cells, immunomodulation, parenchymal regulation (growth, maturation and differentiation of adjacent cells), induction of angiogenesis, scaffolding support of other cells and phagocytic properties. Since CD34+ SFCs are the main reservoir of tissue mesenchymal cells (great mesenchymal potential, probably higher than that proposed for pericytes and other stromal cells), we dedicate a broad section to explain their in vivo behaviour during proliferation and differentiation in different physiologic and pathologic conditions, in addition to their characteristics in the human tissues of origin (adult stem cell niches); G) Involvement in pathological processes, e.g., repair (regeneration and repair through granulation tissue), fibrosis, tumour stroma formation and possible CD34+ SFC-derived tumours (e.g., solitary fibrous tumour, dermatofibrosarcoma protuberans, giant cell fibroblastoma, nuchal-type fibroma, mammary and extramammary myofibroblastoma, spindle and pleomorphic cell lipoma, and elastofibroma) and H) Clinical and therapeutic implications.

Lectin histochemistry as a tool to identify apoptotic cells in the seminiferous epithelium of Syrian hamster (Mesocricetus auratus) subjected to short photoperiod.

Lectins have been widely used to study the pattern of cellular glycoconjugates in numerous species. In the process of cellular apoptosis, it has been observed that changes occur in the membrane sugar sequences of these apoptotic cells. The aim of our work was to identify which lectins, out of an extensive battery of the same (PNA, SBA, HPA, LTA, Con-A, UEA-I, WGA, DBA, MAA, GNA, AAA, SNA), show affinity for germinal cells in apoptosis, at what stage of cell death they do so and in which germinal cell types they can be detected. For this, we studied testis sections during testicular regression in Syrian hamster (Mesocricetus auratus) subjected to short photoperiod. Several lectins showed an affinity for the glycoconjugate residues of germ cells in apoptosis: Gal ß1,3-GalNAcα1, α-d-mannose, N-acetylgalactosamine and l-fucose. Furthermore, lectin specificity was observed for some specific germinal cells and in certain stages of apoptosis. It was also observed that one of these lectins (PNA) showed affinity for Sertoli cells undergoing apoptosis. Therefore, we conclude that the use of lectin histochemistry could be a very useful tool for studying apoptosis in the seminiferous epithelium because of the specificity shown towards germinal cells in pathological or experimentally induced epithelial depletion models.

Ultrastructure of myopericytoma: a continuum of transitional phenotypes of myopericytes.

The authors report the ultrastructural characteristics of myopericytoma, a recently described variant of perivascular (pericytic) tumors, mainly with regard to their myopericytic cells and vessels. Myopericytes range between pericytes and vascular smooth muscle cells (SMCs) in a morphologic continuum. The principal findings of the intermediate phenotypes are (1) elongated or annular morphology with processes of varying length and thickness (usually long and thin); (2) a continuous, irregularly thickened and zonally duplicated basement membrane; (3) heterocellular "peg and socket" junctions with neighboring endothelial cells, and scarce specialized junctions between myopericytes; (4) numerous micropinocytotic vesicles, whether continuous or forming focal rows; (5) abundant thin microfilaments, grouped in bundles with dense bodies and adhesion plaques; (6) poorly developed synthetic system (RER and Golgi); (7) pseudointracellular bodies formed by invagination of basement and plasma membranes, with numerous endocytic vesicles; and (8) zones of cytoplasmic rarefaction near micropinocytotic vesicles and intracellular organelles. The ultrastructure of myopericytes therefore makes it possible to distinguish them from pericytes, SMCs, and fibroblast/myofibroblasts, which is useful for myopericytoma diagnosis. The main pattern of the vessels, with perivascular concentric and multilayered growth of myopericytes (a thick wall in contrast to a small lumen) and lack of elastic material, also supports an intermediate form between pericytic and muscular microvasculature. The presence of myopericytes more similar to SMCs and of hemangiopericytoma-like vessels concurs with transitional forms with angioleyomyoma and true hemangiopericytoma, histogenetically representing a morphologic continuum for the perivascular tumors.

Peg-and-socket junctions between smooth muscle cells and endothelial cells in femoral veins are stimulated to angiogenesis by prostaglandin E2 and glycerols.

The administration of prostaglandin (PG) E2, triacetylglycerol and glycerol induce the formation of numerous vascular buds arising from the femoral vein, as previously demonstrated by our group. In the present study, a great number of peg-and-socket junctions (PSJs) between smooth muscle cells (SMCs) (providing the pegs) and ECs (forming the sockets) were demonstrated. At the first stage, days 1 to 3, PSJs connect subendothelial penetrating processes from activated SMCs with activated ECs of the intima. Subsequently, during angiogenesis (days 4 to 6), SMCs, showing transitional aspects with pericytes, also form PSJs with intimal ECs, but also new PSJs between SMCs and sprouting ECs in the media layer were now observed. Immunohistochemically, α-smooth muscle actin (α-SMA) and H-caldesmon are positive in the cytoplasm of the SMCs, showing a higher expression in pegs. Desmin, however, although it is also positive in the cytoplasm of the SMCs, is negative in the pegs. The expression of CD34 in ECs reveals abundant positive folding that appears to correspond to the sockets. The peculiar expression of caldesmon, whose isoforms may contribute to the regulation of cell motility, and to vasculogenesis and angiogenesis, may have a role in the different mechanisms by which PSJs act in the vein wall.

Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche.

We review the morphofunctional characteristics of pericytes and report our observations. After a brief historical background, we consider the following aspects of pericytes: A) Origin in embryonic vasculogenesis (mesenchymal stem cells, neurocrest and other possible sources) and in embryonic and postnatal life angiogenesis (pre-existing pericytes, fibroblast/ myofibroblasts and circulating progenitor cells). B) Location in pericytic microvasculature and in the other blood vessels (including transitional cell forms and absence in lymphatic vessels), incidence (differences depending on species, topographical location, and type and stage of vessels) and distribution (specific polarities) in blood vessels. C) Morphology (cell body, and longitudinal and circumferential cytoplasmic processes), structure (nucleus, cytoplasmic organelles and distribution of microtubules, intermediate filaments and microfilaments) and surface (caveolae system). D) Basement membrane disposition, formation, components and functions. E) Contacts with endothelial cells (ECs) (peg and socket arrangements, adherent junctions and gap junctions) and with basal membrane (adhesion plaques). F) Molecular expression (pericyte marker identification). G) Functions, such as vessel stabilization, regulation of vascular tone and maintenance of local and tissue homeostasis (contractile capacity and vessel permeability regulation), matrix protein synthesis, macrophage-like properties, immunological defense, intervention in coagulation, participation in mechanisms that regulate the quiescent and angiogenic stages of blood vessels (including the behaviour of pericytes during sprouting angiogenesis and intussuceptive vascular growth, as well as pericyte interactions with endothelium and other cells, and with extracellular matrix) and plasticity, as progenitor cells with great mesenchymal potential, originating other pericytes, fibroblast/myofibroblasts, preadipocytes, chondroblasts, osteoblasts, odontoblasts, vascular smooth muscle and myointimal cells. This mesenchymal capacity is seen in a broad section on the perivascular mesenchymal cell niche hypothesis and in the concept of pericyte and EC "marriage and divorce". H) Peculiar pericyte types, such as hepatic stellate cells (Ito cells), bone marrow reticular cells and mesangial cells. I) Involvement in pathological processes, such as repair through granulation tissue, pericyte-derived tumors, tumor angiogenesis and tumoral cell metastasis, diabetic microangiopathy, fibrosis, atherosclerosis and calcific vasculopathy, lymphedema distichiasis, chronic venous insufficiency, pulmonary hypertension, Alzheimer disease and multiple sclerosis. J) Clinical and therapeutic implications (de-stabilization of vessels or formation of a stable vasculature).

Cell contribution of vasa-vasorum to early arterial intimal thickening formation.

In occluded femoral artery segments, intimal thickening occurred and abundant neovascularization from the surrounding microcirculation developed. Under these conditions, the contribution of vasa-vasorum as a source of supplementary population of cells during the early intimal thickening formation was studied. Using a technique that specifically labels venules, predominantly postcapillary venules, a marker-Monastral Blue B-was used as a tracer to follow the pericyte, endothelial cell and monocyte/macrophage lineages. In the first two days of the experiment, the marker was restricted to the wall of the periarterial microcirculation, being incorporated by endothelial cells, pericytes and some monocytes/macrophages crossing the venule walls. Later, the marker continues to be observed in some of the following cells: endothelial cells and pericytes of the newly-formed vessels, fibroblast-like cells, transitional cells between pericytes and fibroblast-like cells, macrophages migrating into the interstitium, myointimal cells and neoendothelial cells of the arterial lumen. These findings provide evidence that, during arterial intimal thickening formation in occluded arterial segments, the periarterial microvascularization contributes, in addition to recruited macrophages, newly-formed endothelial cells and a supplementary population of fibroblast-like cells and myointimal cells.

Adult stem and transit-amplifying cell location.

Adult stem cells (ASC)--able to self renew and to intervene in maintaining the structural and functional integrity of their original tissue--can express greater plasticity than traditionally attributed to them, adopting functional phenotypes and expression profiles of cells from other tissues. Therefore, they could be useful to regenerative medicine and tissue engineering. Transit-amplifying cells (TAC) are committed progenitors among the ASC and their terminally differentiated daughter cells. The ASC reside in a specialized physical location named niche, which constitutes a three-dimensional microenviroment where ASC and TAC are protected and controlled in their self-renewing capacity and differentiation. The niche can be located near or far from the recruitment point, requiring a short or long-distance cellular migration, respectively. This paper briefly reviews the current status of research about ASC plasticity, transdifferentiation, fusion and functional adaptation mechanisms. Subsequently, ASC and TAC occurrence, characteristics and location have been considered in the skin, cornea, respiratory tract, teeth, gastrointestinal tract, liver, pancreas, salivary glands, kidney, breast, prostate, endometrium, mesenchyma, bone marrow, skeletal and cardiac muscle, nervous system and pituitary gland. Moreover, the role of cancer ASC has also been revised.

Planimetric and histological study of the aortae in atherosclerotic chickens treated with nifedipine, verapamil and diltiazem.

Calcium appears to be involved in many of the cellular events which are thought to be important in atherogenesis. Calcium channel blockers have been shown to reduce arterial lipid accumulation in animals without altering serum cholesterol. Avian models of atherosclerosis offer economic and technical advantages over mammalian models. In this study, we examine the effects of nifedipine, verapamil and diltiazem at clinical and higher doses, on the extent of atherosclerosis of egg-fed chickens. In order to assess the extent of atherosclerosis quantitatively, the aortic lesions of the thoracic and abdominal aorta, aortic arch and supraaortic regions were measured by planimetry. Atherosclerotic lesions were evaluated histologically. Statistically significant reductions in the lipid deposition of the aorta were found in all the treated groups. The extent and distribution of atherosclerotic lesions were decreased in a significant way by verapamil, nifedipine and diltiazem. The higher the dosage used, the higher the regression of the atherosclerotic lesions. At clinical dosage, nifedipine showed the highest decrease of the lesions. In addition, the chicken atherosclerosis model has proved itself useful and very suitable for in vivo drug intervention studies.

Arterial wall neovascularization induced by glycerol.

An intense and significant neovascularization, with numerous capillaries growing into the media layer of the rat femoral artery, was demonstrated when glycerol was administered into the interstitium between the femoral vein and the femoral artery. The maximum microvascularization was observed at days 7 and 9 after glycerol administration. Afterwards, involution of the majority of the newly-formed microvessels in the arterial wall occurred. Other substances containing glycerol in their molecules, such as triacetyl-glycerol and tributyril-glycerol, failed to produce significant neovascularization in the media layer of the femoral artery. Neovascularization of the arterial wall was preceded by a considerable decrease in the number of the smooth muscle cells, which experienced apoptosis and necrobiosis, disappearing in extense areas of the arterial segment affected by glycerol. Coinciding with neovascularization and microvascular involution, repopulation of the media layer by smooth muscle cells was observed.

Galactosides and sialylgalactosides in O-linked oligosaccharides of the primordial germ cells in Xenopus embryos.

The primordial germ cells (PGCs) are covered by surface glycoconjugates; some of them, like galactose residues recognized by peanut agglutinin (PNA), have been reported to be implicated in the PGC migration process. The aim of this work was the characterization of galactosides and sialylgalactosides in N- and O-linked oligosaccharides of Xenopus PGCs. Galactose(Gal)- and sialic acid(Neu5Ac)-binding lectin cytochemistry, in combination with chemical and enzymatic deglycosylation methods, were used. PGCs were slightly labeled with PNA, RCA-I and BSI-B4, which suggests the presence of the sequences Gal(beta1,4)GlcNAc and Gal(alpha1,3)Gal. Moreover, there was no labeling when beta-elimination pre-treatment was performed, suggesting that galactosides were in O-linked oligosaccharides. The strong staining with DSA was probably due to GlcNAc. Furthermore, sialylgalactosides with the sequence Neu5Ac(alpha2,3)Gal(beta1,4)GlcNAc in O-linked oligosaccharides have been shown by means of MAA, PNA and RCA-I.

Glycan composition of follicle (Sertoli) cells of the amphibian Pleurodeles waltl. A lectin histochemical study.

The glycan composition of the N- and O-linked oligosaccharides of the follicle (Sertoli) cells of the urodele amphibian Pleurodeles waltl testis were identified by lectin histochemistry, performed alone or in combination with enzymatic and chemical deglycosylation methods. The follicle cells were shown to contain: (1) Fuc, Galbeta(1,4)GlcNAc, GalNAc and Neu5Acalpha(2,3)Galbeta(1,4)GlcNAc in both N- and O-linked oligosaccharides; (2) Man in N-linked glycans; and (3) Galbeta(1,3)GalNAc in O-linked sugar chains. The follicle cells at the pre- and postmeiotic stages showed some differences in the UEA-1-positive Fuc characterisation, suggesting differences in the glycan composition. In addition, the sequence Neu5Acalpha(2,6)Gal/GalNAc was shown in the follicle cells only after spermiation, in the sperm-empty lobules of the developing glandular tissue. These results suggest that the follicle cells modify their glycoprotein content, probably for the performance of new roles, as the spermatogenetic cells develop. Thus the follicle cells surrounding male germ cells at different spermatogenetic stages would contain different glycoproteins involved in specific roles during male germ cell proliferation and maturation.