VEGF and its role in the early development of the long bone epiphysis

In long bones of murine species, undisturbed development of the epiphysis depends on the generation of vascularized cartilage canals shortly after birth. Despite its importance, it is still under discussion how this event is exactly regulated. It was suggested previously that, following increased hypoxia in the epiphyseal core, angiogenic factors are expressed and hence stimulate the ingrowth of the vascularized canals. In the present study, we tested this model and examined the spatio‐temporal distribution of two angiogenic molecules during early development in mice. In addition, we investigated the onset of cartilage hypertrophy and mineralization. Our results provide evidence that the vascular endothelial growth factor is expressed in the epiphyseal resting cartilage prior to the moment of canal formation and is continuously expressed until the establishment of a large secondary ossification centre. Interestingly, we found no expression of secretoneurin before the establishment of the canals although this factor attracts blood vessels under hypoxic conditions. Epiphyseal development further involves maturation of the resting chondrocytes into hypertrophic ones, associated with the mineralization of the cartilage matrix and eventual death of the latter cells. Our results suggest that vascular endothelial growth factor is the critical molecule for the generation of the epiphyseal vascular network in mice long bones. Secretoneurin, however, does not appear to be a player in this event. Hypertrophic chondrocytes undergo cell death by a mechanism interpreted as chondroptosis.     

Axial vascularization of a large volume calcium phosphate ceramic bone substitute in the sheep AV loop model

Vascularization still remains an obstacle to engineering of bone tissue with clinically relevant dimensions. Our aim was to induce axial vascularization in a large volume of a clinically approved biphasic calcium phosphate ceramic by transferring the arteriovenous (AV) loop approach to a large animal model. HA/β‐TCP granula were mixed with fibrin gel for a total volume of 16 cm³, followed by incorporation into an isolation chamber together with an AV loop. The chambers were implanted into the groins of merino sheep and the development of vascularization was monitored by sequential non‐invasive magnetic resonance imaging (MRI). The chambers were explanted after 6 and 12 weeks, the pedicle was perfused with contrast agent and specimens were subjected to micro‐computed tomography (µ‐CT) scan and histological analysis. Sequential MRI demonstrated a significantly increased perfusion in the HA/β‐TCP matrices over time. Micro‐CT scans and histology confirmed successful axial vascularization of HA/β‐TCP constructs. This study demonstrates, for the first time, successful axial vascularization of a clinically approved bone substitute with a significant volume in a large animal model by means of a microsurgically created AV loop, thus paving the way for the first microsurgical transplantation of a tissue‐engineered, axially vascularized bone with clinically relevant dimensions. Copyright © 2009 John Wiley & Sons, Ltd.     

First-trimester placental vascular development in multiparous women differs from that in nulliparous women

Objective: Multiparas differ from nulliparas by delivering larger babies with larger placentas and by having a lower risk of developing placental syndromes. We postulate that these differences result from a different initial course of placental vascular development.

Study design: We measured placental flow index (FI), vascularization index (VI) and placental volume by 3D power Doppler and obtained blood samples at 8, 10 and 12 weeks pregnancy in 34 healthy nulliparous and 16 multiparous women with an uneventful pregnancy.

Results: Between 8 and 12 weeks multiparas differed from nulliparas in a more rapid initial rise in FI, a higher angiopoietin-2 (ang2) level at eight weeks and no decline in the VEGF/sVEGF-R ratio. Nevertheless, at 12 weeks the FI and placental volume were indistinguishable between both study groups.

Conclusions: These results combining serially measured placental vascularization, placental volume and circulating angiogenetic factors show initial differences in placental development, that howeve, did not maintain till the end of first trimester. The results support the concept that early placental vascular development differs between nulliparas and multiparas. Nevertheless, it is unclear whether these differences contribute to the development later on in pregnancy of intergroup differences in birthweight and incidence of placental syndromes.     

Vascularization of the gastrointestinal tract of the bottlenose dolphin (Tursiops truncatus,Montagu 1821)

Odontocetes primarily rely on fish, cephalopods, and crustaceans as their main source of nutrition. In the digestive system, their polygastric complex exhibits similarities to that of their closest terrestrial relatives such as cows, sheep, and giraffes, while the entero-colic tract shares similarities with terrestrial carnivores. The morphology, caliber, and structure of the odontocete intestine are relatively constant, and, since there is no caecum, a distinction between the small and large intestine and their respective subdivisions is difficult. To address this issue, we used the intestinal vascularization pattern, specifically the course and branching of the celiac artery (CA) and the cranial and caudal mesenteric arteries (CrMA and CdMA). A series of pictures and dissections of 10 bottlenose dolphins (Tursiops truncatus) were analyzed. Additionally, we performed a cast by injecting colored polyurethane foam in both arteries and veins to measure the caliber of the arteries and clarify their monopodial or dichotomous branching. Our results showed the presence of multiple duodenal arteries (DAs) detaching from the CA. The CrMA gave origin to multiple jejunal arteries, an ileocolic artery (ICA), and, in six cases, a CdMA. In four specimens, the CdMA directly originated from the abdominal aorta. The ICA gave rise to the mesenteric ileal branches (MIB) and mesenteric anti-ileal branches and the right colic arteries (RCA) and the middle colic arteries. From the CdMA originated the left colic and cranial rectal arteries (LCA and CrRA). The measurements revealed a mixed monopodial and dichotomous branching scheme. The analysis of the arteries and their branching gave us an instrument, based on comparative anatomy, to distinguish between the different intestinal compartments. We used the midpoint of anastomoses between MIB and RCA to indicate the border between the small and the large intestine, and the midpoint of anastomoses between LCA and CrRA, to tell the colon from the rectum. This pattern suggested an elongation of the duodenum and a shortening of the colic tract that is still present in this species. These findings might be related to the crucial need to possess a long duodenal tract to digest prey ingested whole without chewing. A short aboral part is also functional to avoid gas-producing colic fermentation. The rare origin of the CdMA on the CrMA might instead be a consequence of the cranial thrust of the abdominopelvic organs related to the loss of the pelvic girdle that occurred during the evolution of cetaceans.     

Embryological study of the glottic site and clinical implications

The development of the glottic site, in particular of its ventral area, was studied to better understand the spreading pathways of T1, T2 cancer.

Serial sections of larynges from human embryos, fetuses and adults were observed.

A dorsal, a ventral and an intermediate compartment were found on the basis of their maturation schedule. A commissure muscle which develops in the anterior one third of the glottic site and wraps the connection system of vocal ligaments was recognized. The inferior paraglottic space, the compartment structures and the localization of superficial and deep blood vessels and of glands in the ventral compartment and the components of Broyles ligament were studied during ontogenesis.

The compartments identified here have clinical and oncological relevance. Their detailed knowledge offers a prerequisite for planning and performing compartment conservative surgery in T1, T2 cancer, based on their spreading pathways.     

Vascularization of free Periosteal and 100 Micron Thick Osteoperiosteal Grafts in Muscle Tissue Environment

The vascularization of free periosteal and 100 micron thick osteoperiosteal grafts was studied in growing rabbits. Sixteen rabbits with 32 periosteal and 32 osteoperiosteal grafts were operated upon and microangiographed 1–21 days postoperatively. the vascularization of free periosteal grafts started 1 day postoperatively and that of osteoperiosteal grafts 3 days postoperatively. the first capillaries seemed to enter through the cambium layer in periosteal grafts and through the cortex in osteoperiosteal grafts.     

Radiological anatomy of the vascularization of cranial dural arteriovenous malformations

Summary Knowledge of the radiological anatomy of the cranial durai vascularization allows a flexible and appropriate approach to the pretherapeutic investigation of cranial durai arteriovenous malformations. The variability of the origin of these arteries requires that several possible sources of vascular supply be investigated — internal carotid, internal maxillary, ascending pharyngeal, occipital and vertebral — and that each of their meningeal branches be known in detail. Finally, familiarity with the radiological anatomy of these vessels allows one to identify on routine angiography those vessels that may be a source of risk when performing techniques of endovascular therapy (pedicles supplying the cranial nerves, internal carotid and vertebral anastomoses).Each foramen at the base and vault of the cranium contains an artery to the dura mater. Accordingly, very precise topographical study, in particular of the cavernous region, can be made.

---

Bases radio-anatomiques de la vascularisation des malformations artério-veineuses durales crâniennes

Résumé Les bases radio-anatomiques de la vascularisation durale crânienne permettent de conduire de façon flexible et adaptée à chaque cas l'étude pré-thérapeutique des MAVD crâniennes. La variabilité d'origine de ces artères impose l'exploration de plusieurs sources possibles: carotidienne interne, maxillaire interne, pharyngienne ascendante, occipitale, vertébrale, et la connaissance précise de chacune de leurs branches méningées. La visualisation en routine angiographique des vaisseaux dangereux pour les techniques thérapeutiques endovasculaires (pédicules nourriciers des nerfs crâniens, anastomoses carotidienne interne, vertébrale).Chaque orifice de la base et de la voûte du crâne contient une artère à destinée durale; on peut ainsi arriver à une étude topographique extrêmement précise, en particulier dans la région caverneuse.

     

内皮克隆形成细胞的研究进展

内皮克隆形成细胞(endothelial colony-forming cells,ECFCs)是一种有别于经典内皮祖细胞的具有强大血管新 生功能的晚期内皮祖细胞。ECFCs在心、肺、脑的缺血修复中具有强大的血管生成潜能,在缺血肢体及损伤骨组织 的修复中能明显诱导血管相关因子的表达并促进血管新生。ECFCs具有强大的肿瘤归巢效应,与肿瘤的发生发展及 预后关系密切,可为血管再生研究、肿瘤治疗、组织再生工程等领域提供新的方向。     

沉默CCL19对结直肠癌增殖、迁移、侵袭和促血管形成的影响

目的研究趋化因子CCL19在结直肠肿瘤中的作用。方法采用Real—TimePCR和Westernblotting技术筛选高表达CCL19的细胞株SW620细胞作为研究对象,并用siRNA沉默SW620中的CCL19基因。分别采用细胞增殖实验、Transwell迁移、侵袭实验和小管形成实验来检测SW620细胞的增殖、迁移、侵袭和促血管形成能力的变化。结果Westernblotting和Real—TimePCR证实SW620中CCL19相对其他细胞株高表达。经siRNA-CCL19干扰后,SW620细胞在48～120h内细胞增殖能力显著上升（P〈0．05）,细胞迁移、侵袭能力亦明显上升（P〈0．05）,促血管形成能力明显增强。结论SW620是相对高表达CCL19的细胞株,沉默CCL19基因后可以明显促进SW620细胞在体外的增殖、迁移、侵袭和促血管形成能力,因此认为CCL19在结直肠癌发展中起着抑制作用,并有应用于抗癌药物研究的前景。