Dietary arginine supplementation affects microvascular development in the small intestine of early-weaned pigs.

This study was conducted to evaluate the effects of dietary arginine levels on microvascular development of the small intestine in early-weaned pigs. Twenty-four crossbred pigs (5.0 +/- 0.3 kg body weight) were individually housed and randomly allotted to 1 of 3 diets supplemented with 0, 0.7, and 1.2% L-arginine (8 pigs per group). Pigs consumed the diets ad libitum for 10 d. We collected blood samples on d 3, 6, and 10. On d 10, 6 pigs from each group were randomly selected and killed for tissue sample collection. Compared with control pigs, dietary supplementation with 0.7% L-arginine increased (P < 0.05) jejunal concentrations of nitrite and nitrate (stable oxidation products of nitric oxide), intestinal villus height, as well as plasma proline and arginine concentrations on d 6 and 10. Dietary supplementation with 0.7% L-arginine also increased (P < 0.05) immunoreactive expression of CD34 in duodenal submucosa, ileal mucosa and submucosa, and expression of vascular endothelial growth factor (VEGF) in duodenal submucosa, jejunal mucosa and submucosa, and ileal mucosa compared with the control and 1.2% L-arginine supplementation. Dietary supplementation with 1.2% L-arginine increased (P < 0.05) the concentration of jejunal endothelin-1 compared with the control pigs. Immunoexpression of VEGF in duodenal mucosa and plasma lysine concentrations on d 6 and 10 were lower (P < 0.05) in pigs supplemented with 1.2% L-arginine than in unsupplemented pigs. Collectively, these findings indicate that the effects of L-arginine on microvascular development are beneficial at lower levels but have adverse effects at higher intakes. Dietary supplementation with 0.7% L-arginine may be a useful method to improve microvascular development in the small intestine of early-weaned pigs.

Endoglin (CD105) up-regulation in pulmonary microvasculature of ventilated preterm infants.

RATIONALE: Preterm infants exposed to mechanical ventilation and oxygen are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development. Studies have described disruption of microvascular development in BPD, characterized by primitive angioarchitectural patterns reminiscent of the canalicular/saccular stages of lung development. The molecular regulation of this BPD-associated dysangiogenesis remains undetermined. OBJECTIVES: Endoglin (CD105), a hypoxia-inducible transforming growth factor-beta coreceptor, has been implicated as an important regulator of angiogenesis in various neoplastic and nonneoplastic conditions. The aim of this study was to investigate the expression of endoglin and other angiogenesis-related factors in ventilated preterm human lungs. METHODS: We have studied endoglin protein and mRNA expression in postmortem lungs of short-term and long-term ventilated preterm infants. Control subjects were age-matched infants who had lived for less than 1 hour. MEASUREMENTS AND MAIN RESULTS: Lungs of short-term ventilated preterm infants showed significant upregulation of endoglin mRNA and protein levels, immunolocalized to the microvasculature. Similar but more variable endoglin upregulation was noted in lungs of long-term ventilated infants with BPD. The mRNA levels of vascular endothelial growth factor, angiopoietin-1, and their respective receptors were significantly lower in ventilated lungs than in age-matched nonventilated control lungs. CONCLUSIONS: BPD is associated with a shift from traditional angiogenic growth factors (vascular endothelial growth factor, angiopoietin-1) to alternative regulators such as endoglin, which may contribute to BPD-associated microvascular dysangiogenesis.

Impact of size at birth on the microvasculature: the Avon Longitudinal Study of Parents and Children.

BACKGROUND: The impact of early life factors on the microvasculature is relatively unknown. OBJECTIVES: We hypothesized that small birth size may be associated with structural variations in the retinal vasculature in children. METHODS: The Avon Longitudinal Study of Parents and Children followed a cohort of children born in 1991-1992 from birth. The current study included the first 263 children who were systematically screened in the year-12 follow-up. Complete data were available for 166 children with a gestation of > or = 37 weeks. Retinal circulatory measures were evaluated, including retinal microvascular tortuosity and bifurcation optimality deviance, an indicator of abnormal endothelial function. RESULTS: Optimality deviance and retinal tortuosity were higher among those with lower birth weight. Linear regression modeling was used to assess the association of retinal microvascular measures with birth weight. The standardized beta coefficient between optimality deviance and birth weight was -.182 adjusted for gender and age in weeks; additional adjustment for systolic blood pressure and heart rate had little impact on the beta coefficient. A similar association was observed for retinal tortuosity. CONCLUSION: The findings of this study suggest that early life factors may have an important impact on retinal vascular structure, possibly through an adverse effect on endothelial function.

Microvessel-like structures from outgrowth endothelial cells from human peripheral blood in 2-dimensional and 3-dimensional co-cultures with osteoblastic lineage cells.

Tissue regeneration involves complex processes in the interaction between different cell types that control the process of neo-vascularization. In bone, osteoblasts and bone marrow stem cells provide cue elements for the proliferation of endothelial cells, differentiation of endothelial precursors, and the maturation of a vascular network. In this study, we investigated outgrowth endothelial cells (OECs), a potential source of autologous endothelial cells derived from human peripheral blood, in direct 2-dimensional (2-D) and 3-D co-culture systems with cells relevant for the regeneration of bone tissue, such as osteoblasts. In the co-cultures, OECs were evaluated in terms of their stability as an endothelial population at the single cell level using flow cytometry and their ability to establish a pre-vascular network at the light-microscopical and ultra-structural level. In co-cultures with the osteoblast cell line MG63 and with human primary osteoblasts (pOBs), OECs, in contrast to human umbilical vein endothelial cells, formed highly organized microvessel-like structures. These microvessel-like structures included the formation of a vascular lumen with tight junctional complexes at intercellular contacts of endothelial cells. In the co-culture, the formation of this vascular network was achieved in the standard growth medium for OECs. Furthermore, using a rotating culture vessel system, 3-D co-cultures consisting of OECs and pOBs were generated. Based on these observations, we conclude that OECs could provide a valuable source of autologous endothelial cells for the generation of complex tissue-engineered tissues.

Microvessel scaffold with circular microchannels by photoresist melting.

In this research, a new process that integrates the photoresist melting and soft lithography techniques to fabricate microvessel scaffolds with circular microchannels is proposed. The commercial software COMSOL Multiphysics (formerly known as FEMLAB) is the sought after procedure to optimize the structure of the microvessel scaffold. The photolithographic technique is applied to fabricate the negative photoresist THB-120N (JSR Inc.) based microstructure that is followed by melting to the final replica mold with its structure having convex semicircle cross-section. The replica mold is hence used to replicate PDMS to the top and bottom plates of a microvessel scaffold. These two half plates are bonded after having surface treatment by inductive coupled plasma (ICP) to form the complete scaffold with circular microchannels. Finally, the bovine endothelial cells (BEC) are cultured into the scaffold. Encouraging results by semi-dynamic seeding have been observed in this context, depicting the survival of the cells in the scaffold for up to 4 weeks.

Poly(butyl methacrylate-co-methacrylic acid) tissue engineering scaffold with pro-angiogenic potential in vivo.

A poly(butyl methacrylate-co-methacrylic acid) (BMA-MAA) scaffold was fabricated by an in situ polymerization solvent casting/particulate leaching technique. It displayed high porosity (85-90%), pore interconnectivity, and a pore size range of 100-650 microm. Compression testing of the scaffolds demonstrated a dependence of the compressive stiffness on several fabrication variables including the ratio of monomer to salt used during the polymerization, the degree of salt fusion, and the choice of alternative comonomers to BMA. Subcutaneous implantation of BMA-MAA scaffolds in mice revealed an increased level of histological angiogenesis in tissue invading the pores of the scaffold compared to a BMA control, consistent with the prediction that methacrylic acid (MAA) containing copolymer beads are angiogenic in a wound healing context. At postoperative day 21, the capillary density in the BMA-MAA scaffolds was 56 +/- 13/mm(2) as compared to 32 +/- 8/mm(2) for the BMA scaffolds. With further investigation, it is expected that this biomaterial capable of eliciting an angiogenic response will have widespread application in tissue engineering.

Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor.

Lymphatic vessels develop from specialized venous endothelial cells. Using knockout mice, we found that fasting-induced adipose factor (Fiaf) is required for functional partitioning of postnatal intestinal lymphatic and blood vessels. In wild-type animals, levels of intestinal Fiaf expression rise during the first postnatal day and peak at day 2, which coincides with the onset of the lymphatico-venous partitioning abnormality in Fiaf-/- mutants on a mixed 129/SvJ:C57BL/6 genetic background. Fiaf deficiency is not associated with disruption of the blood vasculature or with lymphatic endothelial recruitment of smooth muscle cells. We identified Prox1, a critical regulator of lymphangiogenesis, as a downstream target for Fiaf signaling in the intestinal lymphatic endothelium. This organ-specific lymphovascular abnormality can be rescued by allowing embryonic Fiaf-/- intestinal isografts to develop in Fiaf+/+ recipients.

Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses.

The bone morphogenetic protein (BMP) family of proteins participates in regulation of angiogenesis in physiologic and pathologic conditions. To investigate the molecular mechanisms that contribute to BMP-dependent angiogenic signaling, we performed gene expression profiling of BMP6-treated mouse endothelial cells. We detected 77 mRNAs that were differentially regulated after BMP6 stimulation. Of these, cyclooxygenase 2 (Cox2) was among the most highly up-regulated by BMP stimulation, suggesting a role for Cox2 as a downstream regulator of BMP-induced angiogenesis. Up-regulation of Cox2 by BMP6 was detected at both mRNA and protein levels in endothelial cells, and BMP6 increased production of prostaglandins in a Cox2-dependent fashion. BMP6 up-regulated Cox2 at the transcriptional level through upstream SMAD-binding sites in the Cox2 promoter. Pharmacologic inhibition of Cox2, but not Cox1, blocked BMP6-induced endothelial cell proliferation, migration, and network assembly. BMP6-dependent microvessel outgrowth was markedly attenuated in aortic rings from Cox2-/- mice or after pharmacologic inhibition of Cox2 in aortas from wild-type mice. These results support a necessary role for Cox2 in mediating proangiogenic activities of BMP6. These data indicate that Cox2 may serve as a unifying component downstream from disparate pathways to modulate angiogenic responses in diseases in which neovascularization plays an underlying pathophysiologic role.

Inhibition of pro-angiogenic factors by a lipid-rich shark extract.

This study aimed to determine whether a shark muscle oil-olive oil mixture influences activators of human angiogenesis. The mixture completely abolished the stimulation induced by vascular endothelial growth factor (VEGF), fibroblast growth factor-2, transforming growth factor-beta, and platelet-derived growth factor. This suggests that it may compete with these growth factors for their binding sites on the endothelial cell surface either by binding to the growth factor or by blocking the actual receptor. The possibility of the oil binding to the VEGF receptor was studied through the use of soluble forms of the receptors (VEGF-R1 and VEGF-R2). It was found that the shark oil-olive oil inhibited the formation of the complexes of VEGF with both of the receptors. This could have been because the oil bound to either the VEGF or the receptor or both. To determine which is possible, the shark oil-olive oil was mixed with the receptors. The molecular size of the receptors increased, and these larger forms of the receptor had reduced capacity for complexing with VEGF. Therefore, one mode of potential anti-angiogenic action of the shark muscle oil-olive oil is the inhibition of the activity of a number of stimulatory molecules, including VEGF. This study demonstrates that the blend of shark and olive oils antagonizes VEGF activity by binding to at least two receptors for the factor, thereby inhibiting the activation by the growth factor.

Transient expression of endothelins in the amoeboid microglial cells in the developing rat brain.

Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1 (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in large numbers at birth, but were progressively reduced with age and were undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression in AMC was reduced but the incidence of apoptotic cells was not increased when compared with the control suggesting that this was due to its downregulation that may help regulate the constriction of blood vessels bearing ET-A receptor. AMC were endowed ET-B receptor indicating that ET released by the cells may also act via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1 mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however, remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed to its upregulated expression in vitro may be due to the complexity of the brain tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and OGD treatments may be due to different signaling pathways independently regulating the two isoforms. The present novel finding has added microglia as a new cellular source of ET that may take part in multiple functions including regulating vascular constriction and chemokines release.

JSR photolithography based microvessel scaffold fabrication and cell seeding.

A simple and inexpensive lithograph approach, in which the PMMA polymer was selected to be the substrate, the negative photoresist JSR was employed to form the microchannel structure, was adopted to fabricate the microvessel scaffold. In addition, a soft PDMS based microvessel scaffold was built by using a mold that was made up of the negative photoresist JSR. With O(2) plasma treatment, the PDMS based microvessel scaffold became more hydrophilic such that the cell culture could be easier to conduct. During cell culture, it was found that the fabricated scaffold enabled the bovine endothelial cells (BEC) to statically grow. However, the overall exchange of nutrient and oxygen was inefficient. Dynamic seeding by a novel apparatus was further conducted to have better circulation of culture medium. The bovine endothelial cells could successfully be cultivated in the microvessel scaffold by dynamic seeding.

Structure optimization of microvascular scaffolds.

In this research, a systematic method for the design of a usable microvascular network based on the commercial software FEMLAB is proposed. The design principle comes out to be that the usable network should made up of multi branches with no more than two vertical nodes in individual branch. A special mask was designed to process the microvessel network for experimental verification of velocity uniformity. Accordingly, a simple lithograph approach, in which the PMMA polymer was selected as the substrate, the negative photoresist JSR was employed to form the microchannel structure, was implemented to fabricate the network. Experimental results verified the uniformity of the velocity profile in the microvessel network.

Growth of pulmonary microvasculature in ventilated preterm infants.

RATIONALE: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. OBJECTIVE: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. METHODS: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. MEASUREMENTS: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. MAIN RESULTS: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. CONCLUSIONS: The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.

Emergence of a glomus-like body in the human yolk sac: a microanatomical analysis of its structure.

Since the last decade the Yolk sac (YS) has been a topic of increasing interest due to the growing use of high-resolution sonography in early determination of pregnancy. Human YS shape and diameter are indicators of viability of pregnancy during the early embryonic period. Nevertheless, the major interest concerns the vital function it plays in early embryo growth and development. Two compartments are recognized in this organ: the yolk sac proper and the vitelline stalk. In this study we report the identification and partial characterization of a glomus-like body in the wall of the secondary YS in humans. A detailed structural description is also presented on the time course of formation of this new structure, at precisely sequential stages between 4-8 wk post-conception. The significance of this new compartment on the YS function is analyzed. Light and scanning electron microscopy were used to investigate the microstructure of the YS and the vitelline stalk during the first 8 wk of development. Ten YSs were collected from embryos (aged between 24-50 days) obtained from emergency salpingectomies due to tubal ectopic pregnancy. From 5 wk onward a new structure was observed in the YS located near the apex of the pear-shaped yolk vesicle and closed to the connecting stalk. We designate this differentiation as glomus-like body. This structure is 1-1.5 mm long and merged from a pocket-like structure of the extraembryonic splanchnic mesoderm of the YS wall. It likely represents an area of convergence of the vascular network of the YS wall. Our findings underline the remarkable complexity of the human secondary yolk sac during early development. The detailed description of the microanatomy of this vital organ is of theoretical and practical interest in order to unravel the mechanisms used by the yolk sac to transport nutrients to the embryo.

Growth factors and their receptors: fundamental molecules for human placental development.

In this review we present data concerning the localization of some important growth factors and their receptors in the human placenta. We focus our attention on molecules playing a fundamental role in angiogenesis and morphologic processes as beta-FGF, EGF and TGF-beta. The distribution of these growth factors and their receptors in the placental villi during gestation suggests that these molecules play a pivotal role in growth and differentiation of the villous tree.

TEM-8 and tubule formation in endothelial cells, its potential role of its vW/TM domains.

BACKGROUND AND AIMS: Tumour endothelial marker-8 (TEM-8) has been found to be selectively up regulated in tumour-associated endothelial cells, it is implicated in tumour specific angiogenesis, but its mechanism in angiogenesis is not defined. METHODS: A ribozyme transgene (TEM-8) was cloned into a suitable mammalian expression vector (pc DNA 3.1-GFP-NT) and transfected into HECV cells. Various domains of TEM-8 were designed and cloned into pEF6/V5-His TOPO TA vector and transfected into Chinese Hamster ovarian cells (CHO), which do not form tubules and do not express TEM-8 in general (CHO(vW), CHO(TM), CHO(vW/TM), CHO(AE), CHO(AC), CHO(IC), and CHO(FL) domains, respectively). The effect of TEM-8 knocked out HECV cells was tested (by angiogenesis and migration assays), and the effect of each cleavage domain of TEM-8 was tested by microtubule formation assay. RESULTS: TEM-8 stable transfectants (HECV(DeltaTEM8a)) manifested a complete loss of TEM-8 gene expression at mRNA and protein levels. In contrast, control GFP plasmid (HECV(pControl)) and wild-type HECV cells (HECV(WT)) had similar levels of TEM-8 expression. TEM-8 transfected cell (HECV(DeltaTEM8a)) significantly decreased the micro-vessels formation compared with controls (HECV(pControl)) (mean+/-SE, 20.3+/-4.03 microm; p=0.0086 vs. control 39.5+/-10.1 microm), and migration (38.52+/-2.17; p<0.05 vs. control 80.23+/-3.19), and micro-vessel formation of HECV(DeltaTEM8a) cell was also reduced compared with wild-type (HECV(WT)) (mean+/-SE, 20.3+/-4.03 microm; p=0.0078 vs. wild-type 42.5+/-9.1 microm) and migration (38.52+/-2.17microm; p<0.05 vs. wild-type 82.4+/-4.45 microm). vW together with transmembrane domains of TEM-8 (CHO(vW/TM)) and full-length CHO(FL) showed formation of tubule-like structure in CHO cells, whereas the other domains showed no effect. CONCLUSION: Targeting the TEM-8 gene by way of a hammerhead ribozyme knocks out TEM-8 cells, and is an effective way to reduce the micro-vessel formation or migration potential in tumour-associated endothelial cell through its vW domain. These results suggest that the vW domain together with the transmembrane domain of TEM-8 may play an important biological role in TEM-8 related tubule formation.

A deterministic model of growth factor-induced angiogenesis.

Understanding the formation and structure of a capillary network is critical for any reparative strategy since the capillary network dictates tissue survival, hemodynamics, and mass transport. Vascular assembly and patterning has largely been studied using a reductionist approach where a particular endothelial cell molecular pathway or cellular mechanism is investigated as a relatively closed system. This trend of research has yielded a staggering wealth of genes, proteins, and cells that play critical roles in angiogenesis and some have resulted in successful targeted angiogenic therapies. However, these genes, proteins, and cells do not exist in discrete closed systems, rather they are intimately coupled across spatial and temporal dimensions. Designing experiments to study a single or group of perturbations is fraught with confounding complications. An integrative tool is required that incorporates gene, protein, and cell information and appropriately describes the complex systems behavior of vascular assembly and patterning. In this paper, we propose a new deterministic mathematical formulation to model growth factor-induced angiogenesis. Conductivity of the extracellular matrix for the movement/extension of capillary sprouts is a new concept introduced to account for the heterogeneity and anisotropy of the extracellular matrix. The replacement of traditional endothelial cell density by the capillary indicator function enhances the capabilities of capturing the capillary network sharply in a fine scale (i.e., tracking the dynamics of the tip in uni-cellular scale). Major mechanisms including cell proliferation, sprout branching, and anastomosis are incorporated directly into this continuous mathematical model and model parameters are perturbed to determine the strength of their effect on angiogenesis. The model is fully deterministic and generates the overall dendritic structure of the capillary network morphologically similar to those observed in vivo. The simulations "capture" significant vascular patterning, such as vascular loops and backward growth. Moreover, the simulations provide a deeper understanding of the influence of extracellular matrix on angiogenesis and vascular patterning. An advantage of this model is that the complex physical, chemical and biological processes in angiogenesis can be described and consequently analyzed by a mathematical system with self-contained information.

The roles of tissue engineering and vascularisation in the development of micro-vascular networks: a review.

The construction of tissue-engineered devices for medical applications is now possible in vitro using cell culture and bioreactors. Although methods of incorporating them back into the host are available, current constructs depend purely on diffusion which limits their potential. The absence of a vascular network capable of distributing oxygen and other nutrients within the tissue-engineered device is a major limiting factor in creating vascularised artificial tissues. Though bio-hybrid prostheses such as vascular bypass grafts and skin substitutes have already been developed and are being used clinically, the absence of a capillary bed linking the two systems remains the missing link. In this review, the different approaches currently being or that have been applied to vascularise tissues are identified and discussed.

[Morphometric characteristics of microcirculatory bed of olfactory bulbs in the desympathized albino rat]. / Morfometricheskie kharakteristiki mikrotsirkuliarnogo rusla oboniatel'noi lukovitsy desimpatizirovannoi beloi krysy.

To detect the effect of postnatal chemical desympathization on morphometric characteristics of the vessels of olfactory bulbs in albino rat early postnatal ontogenesis, the study was performed using the histochemical method for demonstration of alkaline phosphatase activity, which is a marker of vascular endothelium, and vessel diameter and relative density were measured during the first three months of life. Desympathization was induced in rats by daily intraperitoneal injection of 60-70 mg/kg of guanethidine during postnatal days 1 to 30. The vessel diameter was found to increase after day 30 simultaneously with the changes of the vascular wall of vessels (irregular contour and non-uniform vasodilatation, non-uniform decrease in alkaline phosphatase activity). Relative density of the vessels was reduced one month after desympathization. After two months this parameter remained depressed in the peripheral zone of the olfactory bulbs, while in the central zone it was not different from that one in control group.

Microvascular development: learning from pancreatic islets.

Microvascular development is determined by the interplay between tissue cells and microvascular endothelial cells. Because the pancreatic islet is an organ composed mainly of endothelial and endocrine cells, it represents a good model tissue for studying microvascular development in the context of a tissue. In this review, we will describe the special morphology of islet capillaries and its role in the physiologic function of islets: secretion of insulin in response to blood glucose levels. We will speculate on how islet-secreted VEGF-A generates a permeable endothelium that allows insulin to pass quickly into the blood stream. In addition, we speculate on how endothelial cells might form a capillary lumen within the islets. At the end, we look at the islet microvasculature from a medical point of view, thus describing its critical role during type I diabetes and islet transplantation.