Renin and ovarian vascularization in cows with follicular cysts after epidural administration of a GnRH analogue

The ovarian renin–angiotensin system may play an important role in follicular growth and maturation, as well as in the process of ovulation. The aim of this study was to investigate the effects of administration of a GnRH analogue to cows with ovarian follicular cysts on plasma renin concentrations and ovarian vascularization. This study was performed with 60 Friesian cows, which were diagnosed with follicular cysts, and randomly allocated into two groups: group A (treatment; n = 30) received 2 ml of lecirelin (Dalmarelin^® – Fatro), per head via sacro-coccygeal epidural, and group B (control; n = 30) received 2 ml saline solution (0.9% NaCl) per head by the same route. Blood samples were immediately collected prior to administration (T0) and then 24 h (T1), 48 h (T2) and 8 days (T3) after administration of the treatment, for both groups. Ovarian vascularization was evaluated utilizing Power Doppler on these same days in 10 animals from each group. The number of pixels detected by Power Doppler was used as an indicator of the degree of vascularization. Plasma renin concentrations remained relatively constant for the control (group B) animals, but increased as the sampling period progressed (NS) for the treated cows (group A). Similarly, there were no changes in ovarian vascularization (number of pixels) for the control cows, but vascularization increased throughout the sampling period in the treated animals. The number of pixels associated with cysts was significantly higher for treated compared to control cows at 24 h after treatment (P < 0.001). The epidural administration of a GnRH analogue was determined to be a highly effective therapy for follicular cysts (regression occurred in 82% of treated cows within 8 ± 2 days after treatment, but in none of the control cows), which also enhanced ovarian vascularization.     

Millimeter‐wave emissivity as a metric for the non‐contact diagnosis of human skin conditions

A half‐space electromagnetic model of human skin over the band 30–300 GHz was constructed and used to model radiometric emissivity. The model showed that the radiometric emissivity rose from 0.4 to 0.8 over this band, with emission being localized to a layer approximately one millimeter deep in the skin. Simulations of skin with differing water contents associated with psoriasis, eczema, malignancy, and thermal burn wounds indicated radiometry could be used as a non‐contact technique to detect and monitor these conditions. The skin emissivity of a sample of 30 healthy volunteers, measured using a 95 GHz radiometer, was found to range from 0.2 to 0.7, and the experimental measurement uncertainty was ±0.002. Men on average were found to have an emissivity 0.046 higher than those of women, a measurement consistent with men having thicker skin than women. The regions of outer wrist and dorsal forearm, where skin is thicker, had emissivities 0.06–0.08 higher than the inner wrist and volar forearms where skin is generally thinner. Recommendations are made to develop a more sophisticated model of the skin and to collect larger data sets to obtain a deeper understanding of the signatures of human skin in the millimeter wave band. Bioelectromagnetics. 38:559–569, 2017. © 2017 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.     

Histological evaluation of the effect of VEGF on auto-transplanted mouse ovaries

One of the most important factors affecting survival rate of ovarian follicles during transplantation period is proper vascular development. The objective of the study was to evaluate the effect of vascular endothelial growth factor (VEGF) on auto-transplanted ovarian tissue. Twenty-one-day-old female mice (n?=?30) transplanted as control group and 21-day-old female mice (n?=?40) were divided into 4 groups that were treated with 0.5, 1, 2 and 4?µg/mL of VEGF directly injected to auto-transplanted ovarian tissue. Twenty-one days after transplantation, mice were treated with 7.5 IU pregnant mare serum gonadotropin and human chorionic gonadotropin. Transplanted ovaries were removed and sections were prepared from transplanted tissues for staining. The most effective dosage of VEGF on transplanted tissue was determined over H&;E (hematoxylin and eosin) staining results. Slides were compared using TUNEL staining and CD31 assay for the most effective dosage. The percentages of preantral and antral follicles were not significantly different between transplanted group with 4?µg/mL VEGF and non-transplanted group. Lower apoptotic areas and higher CD31 expression were observed in transplanted ovaries treated with 4?µg/mL VEGF when compared to transplanted ovaries without VEGF treatment. VEGF positively affects the quality of ovarian tissue during transplantation. Survival rate of follicles and follicular development has improved with the effect of VEGF.     

Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse

Tightly regulated crosstalk between endothelial cells and pericytes is required for formation and maintenance of functional blood vessels. When the NG2 proteoglycan is absent from pericyte surfaces, vascularization of syngeneic tumors growing in the C57Bl/6 mouse brain is aberrant in several respects, resulting in retardation of tumor progression. In the NG2 null mouse brain, pericyte investment of the tumor vascular endothelium is reduced, causing deficiencies in both pericyte and endothelial cell maturation, as well as reduced basal lamina assembly. While part of this deficit may be due to the previously-identified role of NG2 in β1 integrin-dependent periyte/endothelial cell crosstalk, the ablation of NG2 also appears responsible for loss of collagen VI anchorage, in turn leading to reduced collagen IV deposition. Poor functionality of tumor vessels in NG2 null brain is reflected by reduced vessel patency and increased vessel leakiness, resulting in large increases in tumor hypoxia. These findings demonstrate the importance of NG2-dependent pericyte/endothelial cell interaction in the development and maturation of tumor blood vessels, identifying NG2 as a potential target for anti-angiogenic cancer therapy.     

Multiscale tissue engineering for liver reconstruction

The liver is a target of in vitro tissue engineering despite its capability to regenerate in vivo. The construction of liver tissues in vitro remains challenging. In this review, conventional 3D cultures of hepatocytes are first discussed. Recent advances in the 3D culturing of liver cells are then summarized in the context of in vitro liver tissue reconstruction at the micro- and macroscales. The application of microfluidics technology to liver tissue engineering has been introduced as a bottom-up approach performed at the microscale, whereas whole-organ bioengineering technology was introduced as a top-down approach performed at the macroscale. Mesoscale approaches are also discussed in considering the integration of micro- and macroscale approaches. Multiple parallel multiscale liver tissue engineering studies are ongoing; however, no tissue-engineered liver that is appropriate for clinical use has yet been realized. The integration of multiscale tissue engineering studies is essential for further understanding of liver reconstruction strategies.     

Assessing the ability of human endothelial cells derived from induced-pluripotent stem cells to form functional microvasculature in vivo

Forming functional blood vessel networks is a major clinical challenge in the fields of tissue engineering and therapeutic angiogenesis. Cell-based strategies to promote neovascularization have been widely explored, but cell sourcing remains a significant limitation. Induced-pluripotent stem cell-derived endothelial cells (iPSC-ECs) are a promising, potentially autologous, alternative cell source. However, it is unclear whether iPSC-ECs form the same robust microvasculature in vivo documented for other EC sources. In this study, we utilized a well-established in vivo model, in which ECs (iPSC-EC or human umbilical vein endothelial cells [HUVEC]) were coinjected with normal human lung fibroblasts (NHLFs) and a fibrin matrix into the dorsal flank of severe combined immunodeficiency mice to assess their ability to form functional microvasculature. Qualitatively, iPSC-ECs were capable of vessel formation and perfusion and demonstrated similar vessel morphologies to HUVECs. However, quantitatively, iPSC-ECs exhibited a two-fold reduction in vessel density and a three-fold reduction in the number of perfused vessels compared with HUVECs. Further analysis revealed the presence of collagen-IV and α-smooth muscle actin were significantly lower around iPSC-EC/NHLF vasculature than in HUVEC/NHLF implants, suggesting reduced vessel maturity. Collectively, these results demonstrate the need for increased iPSC-EC maturation for clinical translation to be realized.     

Role of oxygenation and vascularization in drug resistance

Oxygenation status and tumor vascularization seem to be important factors in determining therapeutic effectiveness and patient prognosis. An abundance of data on tumor oxygenation and vascularization is available and it clearly shows that most human solid tumors are heterogeneously oxygenated and vascularized. They contain hypoxic regions. Such regions and areas of reduced vascularization can affect the response to a variety of drugs. Direct measurements of pO₂ and the vascular density in various types of tumors have, upon correlation of the data to therapeutic outcome, shown that low pO₂ values and low vascular density are associated with a decreased response to therapy. Therefore, oxygenation status and the extent of tumor vascularization may well be important factors contributing to the difficulty of successful therapy in certain types of tumors. This revised version was published online in August 2006 with corrections to the Cover Date.     

Cell-based approaches to the engineering of vascularized bone tissue

This review summarizes recent efforts to create vascularized bone tissue in vitro and in vivo through the use of cell-based therapy approaches. The treatment of large and recalcitrant bone wounds is a serious clinical problem, and in the United States approximately 10% of all fractures are complicated by delayed union or non-union. Treatment approaches with the use of growth factor and gene delivery have shown some promise, but results are variable and clinical complications have arisen. Cell-based therapies offer the potential to recapitulate key components of the bone-healing cascade, which involves concomitant regeneration of vasculature and new bone tissue. For this reason, osteogenic and vasculogenic cell types have been combined in co-cultures to capitalize on the function of each cell type and to promote heterotypic interactions. Experiments in both two-dimensional and three-dimensional systems have provided insight into the mechanisms by which osteogenic and vasculogenic cells interact to form vascularized bone, and these approaches have been translated to ectopic and orthotopic models in small-animal studies. The knowledge generated by these studies will inform and facilitate the next generation of pre-clinical studies, which are needed to move cell-based orthopaedic repair strategies into the clinic. The science and application of cytotherapy for repair of large and ischemic bone defects is developing rapidly and promises to provide new treatment methods for these challenging clinical problems.