Organogenesis最新文献

Angiogenesis is a physiological procedure during which the new blood vessels develop from the pre-existing vessels. Uncontrolled angiogenesis is related to various diseases including cancers. Clinical inhibition of undesired angiogenesis is still under investigation. We utilized nicotinic acid, a family member of the B-vitamin niacin (vitamin B3) that has been used in the prevention and treatment of atherosclerosis or other lipid-metabolic disorders, to treat human umbilical vein endothelial cells (HUVECs) and chick chorioallantoic membrane (CAM), and investigated its influence on angiogenesis in vitro and in vivo. We found that nicotinic acid could obviously inhibit HUVEC proliferation induced by vascular endothelial growth factor. Both the in vitro and in vivo assays showed that nicotinic acid could significantly inhibit the process of angiogenesis. To further investigate the mechanism underlying the effect of nicotinic acid on angiogenesis, we found that it might function via regulating the cytoskeleton arrangements, especially the rearranging the structures of F-actin and paxillin. In summary, we discovered that nicotinic acid could obviously inhibit the process of angiogenesis by changing the angiogenesis factor expression levels and inducing the cytoskeleton rearrangement of endothelial cells.

Somatic cell nuclear transfer is a technique to create an embryo using an enucleated oocyte and a donor nucleus. Nucleus of somatic cells must be reprogrammed in order to participate in normal development within an enucleated egg. Reprogramming refers to the erasing and remodeling of cellular epigenetic marks to a lower differentiation state. Somatic nuclei must be reprogrammed by factors in the oocyte cytoplasm to a rather totipotent state since the reconstructed embryo must initiate embryo development from the one cell stage to term. In embryos reconstructed by nuclear transfer, the donor genetic material must respond to the cytoplasmic environment of the cytoplast and recapitulate this normal developmental process. Enucleation is critically important for cloning efficiency because may affect the ultrastructure of the remaining cytoplast, thus resulting in a decline or destruction of its cellular compartments. Nonetheless, the effects of in vitro culturing are yet to be fully understood. In vitro oocyte maturation can affect the abundance of specific transcripts and are likely to deplete the developmental competence. The epigenetic modifications established during cellular differentiation are a major factor determining this low efficiency as they act as epigenetic barriers restricting reprogramming of somatic nuclei. In this review we discuss some factors that could impact cell differentiation in embryo generated by nuclear transfer.

Turner's syndrome (TS) is depicted as a total or partial absence of X chromosome, and occurs in approximately 1/2200 of live born females. Generally, mosaic patients are diagnosed following karyotype analysis due to recurrent pregnancy loss, repeated in vitro fertilization (IVF) failure, and a history of malformed babies. The purpose of this case report is to show that even a selection of normal karyotype embryos can result in abnormalities for those with mosaic TS. A 32-year old patient who underwent IVF after ICSI-PGD, and was diagnosed with 45X/46XX karyotype. At the 12-week scan, one of the fetuses had an upper limb hemimelia in one arm, and feticide was applied to that fetus. The patient delivered a healthy, 2980 g female baby at the thirty-eighth week. In mosaic TS pregnancies (even those obtained by ICSI-PGD), fetal anomaly risk is high. Therefore, careful prenatal scanning is needed for these pregnancies.

Patch grafts are widely used in various kind of vascular surgeries such as detect repair or dilation of vascular stenosis. Expanded polytetrafluoroethylene (ePTFE) patches are flexible and handle well, but have shown problems with calcification as they are non-bioabsorbable and therefore permanently remain in the body. It is important to develop an alternative biocompatible patch. Silk fibroin (SF) was developed as a biocompatible material, but it lacks of the elasticity required for surgery as a patch. Polyurethane (PU) is also a well-known elastomer so this study focused on the SF and the PU blend materials with a weight ratio of 5:5 (SF/PU). To evaluate the SF/PU patch, the patches were implanted into the abdominal aortas of rats, using the ePTFE patch in the control group. Because it was more flexible the SF/PU patch was easier to implant than the ePTFE patch. At 1 week after implantation, the SF/PU patch had been infiltrated with cells and collagen fiber. The ePTFE control patch did not accumulate collagen fiber until 3 months and calcification occurred at 4 weeks. The SF/PU patch did not present any signs of calcification for 3 months. This study addressed the problems associated with using SF in isolation and showed that the SF/PU patch can be considered as a useful alternative to the ePTFE to overcome the problem of calcification.

EphB and their ligands ephrin-B are an important family of protein tyrosine kinase receptors involved in thymocyte-thymic epithelial cell interactions known to be key for the maturation of both thymic cell components. In the present study, we have analyzed the maturation of cortical thymic epithelium in EphB-deficient thymuses evaluating the relative relevance of EphB2 and EphB3 in the process. Results support a relationship between the epithelial hypocellularity of mutant thymuses and altered development of thymocytes, lower proportions of cycling thymic epithelial cells and increased epithelial cell apoptosis. Together, these factors induce delayed development of mutant cortical TECs, defined by the expression of different cell markers, i.e. Ly51, CD205, MHCII, CD40 and β5t. Furthermore, although both EphB2 and EphB3 are necessary for cortical thymic epithelial maturation, the relevance of EphB3 is greater since EphB3-/- thymic cortex exhibits a more severe phenotype than that of EphB2-deficient thymuses.

Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a collagen scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair. The collagen scaffold modified with anti-EGFR antibody prevented the inhibition of NSC neuronal differentiation by myelin. After transplantation into completely transected SCI animals, the scaffold-linked antibodies induced production of nascent neurons from endogenous and transplanted NSCs, which rebuilt the neuronal relay by forming connections with each other or host neurons to transmit electrophysiological signals and promote functional recovery. Thus, a scaffold-based strategy for rebuilding the neuronal differentiation microenvironment could be useful for SCI repair.

Endometriosis is defined by the presence of endometrial ectopia. Multiple hypotheses have been postulated to explain the etiology of endometriosis to understand various clinical evidences. The etiology of endometriosis is still unclear.The primary question to understanding the etiology of endometrial ectopia (endometriosis) is determining the origin of eutopic (normally cited) endometrium.According to the new theory, primordial germ cells migrate from hypoblast (yolk sac close to the allantois) to the gonadal ridges. The gonadal ridges which composed of primordial germ cells derive to the: eutopic endometrium, ovary, ovarian ligament and ligamentum teres uteri.There are 2 principal processes in uterine organogenesis: the intersection of gonadal ridges with mesonephral ducts to form the uterine folds with an endometrial cavity and the fusion of the both uterine folds together to form the unicavital (normal) uterus. In the uterine folds there are closer cell-to-cell communications, polypotential germ cells differentiate and grow into myometrium and endometrial layers.Some of the polypotential germ cells fail to reach the ridges and stay in the peritoneal cavity, where they may be transforming into external endometrial heterotopies.The main insight in the etiology of endometriosis is polypotential germ cells origin, which may explain its potency, pathogenesis and expansion.

Supernumerary teeth are common clinical dental anomalies. Although various studies have provided abundant information regarding genes and signaling pathways involved in tooth morphogenesis, which include Wnt, FGF, BMP, and Shh, the molecular mechanism of tooth formation, especially for supernumerary teeth, is still unclear. In the population, some cases of supernumerary teeth are sporadic, while others are syndrome-related with familial hereditary. The prompt and accurate diagnosis of syndrome related supernumerary teeth is quite important for some distinctive disorders. Mice are the most commonly used model system for investigating supernumerary teeth. The upregulation of Wnt and Shh signaling in the dental epithelium results in the formation of multiple supernumerary teeth in mice. Understanding the molecular mechanism of supernumerary teeth is also a component of understanding tooth formation in general and provides clinical guidance for early diagnosis and treatment in the future.

Organ-like microenviroment and 3-dimensional (3D) cell culture conformations have been suggested as promising approaches to mimic in a micro-scale a whole organ cellular functions and interactions present in vivo. We have used this approach to examine biologic features of hepatocellular carcinoma (HCC) cells. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo. We show that the addition of non-parenchymal cells such as fibroblast and endothelial cells is required for spheroid formation as well as the maintenance of the tissue-like structure. Furthermore, HCC cells cultured as spheroids with non-parenchymal cells express more neo-angiogenesis-related markers (VEGFR2, VEGF, HIF-α), tumor-related inflammatory factors (CXCR4, CXCL12, TNF-α) and molecules-related to induced epithelial-mesenchymal transition (TGFβ, Vimentin, MMP9) compared with organoids containing only HCC cells. These results demonstrate the importance of non-parenchymal cells in the cellular composition of HCC organoids. The novelty of the multicellular-based organotypic culture system strongly supports the integration of this approach in a high throughput approach to identified patient-specific HCC malignancy and accurate anti-tumor therapy screening after surgery.