含IKVAV肽体内诱导血管生成的实验研究*

目的探讨含IKVAV肽体内自组装成凝胶材料诱导血管生成的可行性。方法实验组:配制1%的肽溶液,pH=9．0。对照组:配制16．67%的明胶,pH=7．4。各取1毫升,分别注射植入大鼠背部脊柱两侧皮下。观察植入后一周内鼠的全身反应及植入部位的皮肤变化。结果二周后取材,固定,常规HE染色及VEGF免疫组织化学染色。术后一周实验动物存活良好,无全身不良反应,植入部位皮肤无红肿、无坏死。实验组:植入点的1%的肽自组装成凝胶,HE染色显示,凝胶与周围组织间整合好,无炎性细胞浸润,周围有血管长入凝胶内部,血管腔内可发现红细胞,术后两周,VEGF免疫组织化学染色阳性。对照组:HE染色,明胶与组织的相容性好,在明胶内未发现血管;VEGF免疫组织化学染色阴性。结论含IKVAV肽体内可自组装成凝胶,并且可诱导新生血管在凝胶内生成。     

自噬与肿瘤血管生成的研究进展

自噬（autophagy）是一种特殊的细胞过程,可通过将自身受损的细胞器和大分子物质转运至溶酶体并降解,参与调控细胞存活、生长、分化和内环境稳态的维持,在生命过程的各个方面均起着非常重要的作用。研究结果发现,自噬在肿瘤发生、发展及转移过程中起着重要作用,其与血管内皮生长因子协同作用促进肿瘤的血管生成和细胞修复,且可能在...     

肿瘤血管生成和抗血管生成治疗的研究进展

肿瘤组织中的新生血管是保证肿瘤持续生长所必需的,也是肿瘤转移的重要途径之一.针对促进肿瘤血管生成和血管生成抑制物制定新策略,采用合适手段与方法,抑制肿瘤内血管新生,消除或减少肿瘤内原有血管,可达到治愈肿瘤的目的.     

血管生长素与血管生成

血管生长素 (ANG)属于RNase超家族 ,是唯一具有核糖核酸酶活性的血管生成因子。它可通过促进基膜的降解 ,促进内皮细胞增殖、迁移、粘附等作用来促进血管生成。ANG在多种肿瘤中表达增高。在糖尿病、外周动脉阻塞性疾病中其表达水平亦有升高     

血管生成及靶向治疗

血管是胚胎发育第一器官并形成人体最大网络系统。正常血管生成受到各种细胞因子的严格控制。异常的血管生成导致各种疾病,例如肿瘤、糖尿病、免疫病、先兆子痫、肢体缺血等。因此,血管生成已成为治疗这些疾病的药物靶点。2004年,第一个抗血管生成药物用于结肠癌的治疗,标志着抗血管生成疗法的成功。然而,随着血管生成药物的临床应用,新的问题也逐渐显露出来。这不仅给我们提出了新的挑战,而且展现出新的希望。     

套入式血管生成的研究进展

套入式血管生成是20多年前发现的一种新的血管生成方式。本文从其发现过程、连续性生成过程、影响因素及生成形式等几个方面对套入式血管生成方式的研究状况做一总结。     

血管生成抑制剂Canstatin研究概况

人血管能抑素Canstatin是近年发现的血管生成抑制剂,具有强大的抑制血管生成作用.本文综述了该药的发现命名、生物学效应、作用机制、应用前景.     

卵巢癌血管生成的多样性

新血管生成在个体发育、创伤愈合等过程中起着至关重要的作用,也是肿瘤生存、转移、复发的组织基础[1].研究表明,少数极恶性肿瘤存在血管生成(angiogenesis)、血管形成(vasculogenesis)和血管生成拟态(vasculogenic mimicry)等方式,多种血管新生方式与肿瘤的转移、复发等恶性生物行为密切相关.卵巢癌的死亡率在女性生殖道癌瘤中居首位,患者5年生存率长期徘徊在30%左右,最新研究证实,卵巢恶性肿瘤血管生成具有多样性,本文将就卵巢癌不同血管生成方式的研究进展及其与卵巢恶性生物学行为的关系进行综述.     

骨生物支架材料诱导的血管生成

背景：生物支架材料诱导建立的血管网络对于细胞存活和新骨形成是至关重要的。近年来,骨组织工程的学者们更多地关注了骨再生过程中不同支架材料对血管生成的影响。目的：阐述能促进血管生成骨生物支架材料的特点及其在促血管化过程中的作用。方法：由第一作者以“Osteogenesis、Biomaterials、bone defect、Angiogenesis、vascularization”为英文检索词,以“成骨分化、生物材料、骨缺损、血管生成、血管化”为中文检索词,检索 PubMed、知网数据库中 2016 至 2020 年已发表的相关文献,并进行筛选、归纳与总结,最终纳入 82篇相关文献进行综述。 结果与结论：支架材料植入后建立的早期血管网络能够提供足够的营养并运输代谢物质,如果局部血管网络形成缓慢造成血液供应缺乏,将导致成骨过程的延迟甚至无法形成新骨。研究人员通过改变支架材料理化性质、负载生长因子缓释系统、结合微量元素或模拟骨膜结构等方式对支架材料进行修饰,使其在诱导骨再生过程中能促进早期血管生成,有利于整个骨再生过程。但受限于当前制造技术及缺乏相关基础研究,目前生物支架材料更多在于对支架材料单一因素的改变进行研究。未来随着制造技术的提升及更多新型生物材料的研发,将制作出集多尺寸孔隙结构、微/纳米级多层级表面形貌为一体的生物支架材料,同时随着对体内骨再生过程中各生长因子分泌释放的精确性研究,以及对缓释、控释系统的精确把握,也将进一步提升生物支架材料的促血管生成作用。https://orcid.org/0000-0002-7058-2101 (李杜晨晖) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

肿瘤血管生成研究进展

血管生成是肿瘤生长和转移的重要原因,如能找到有效调节血管生成的途径,则有望控制肿瘤的生长和转移。本文综述了血管生成的分子生物学机制,以及几种有前途的抗血管生成药物的基础和临床研究进展。     

Tripterygium wilfordii Inhibiting Angiogenesis for Rheumatoid Arthritis Treatment

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a serious pre-vascular inflammatory phase, followed by significant increase in vessel growth. Inhibition of angiogenesis is a novel therapeutic strategy against RA. The Chinese herbal remedy Tripterygium wilfordii, Hook. f. (TwHf) has been reported to be therapeutically efficacious in the treatment of RA. Recent studies have revealed that treatment with TwHf extracts inhibit angiogenesis of RA, thereby elaborately attenuation RA symptom. This review mainly addresses the anti-angiogenesis effect of TwHf in treatment of RA.     

Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction

Stem cell therapy has been proved to be an effective approach to ameliorate the heart remodeling post myocardial infarction (MI). However, poor cell engraftment and survival in ischemic myocardium limits the successful use of cellular therapy for treating MI. Here, we sought to transplant adipose derived-mesenchymal stem cells (AD-MSCs) with a hydrogel (NapFF-NO), naphthalene covalently conjugated a short peptide, FFGGG, and β-galactose caged nitric oxide (NO) donor, which can release NO molecule in response to β-galactosidase. AD-MSCs, either from transgenic mice that constitutively express GFP and firefly luciferase (Fluc), or express Fluc under the control of VEGFR2 promoter, were co-transplanted with NapFF-NO hydrogel into murine MI models. Improved cell survival and enhanced cardiac function were confirmed by bioluminescence imaging (BLI) and echocardiogram respectively. Moreover, increasing VEGFR2-luc expression was also tracked in real-time in vivo, indicating NapFF-NO hydrogel stimulated VEGF secretion of AD-MSCs. To investigate the therapeutic mechanism of NapFF-NO hydrogel, cell migration assay, paracrine action of AD-MSCs, and histology analysis were carried out. Our results revealed that condition medium from AD-MSCs cultured with NapFF-NO hydrogel could promote endothelial cell migration. Additionally, AD-MSCs showed significant improvement secretion of angiogenic factors VEGF and SDF-1α in the presence of NapFF-NO hydrogel. Finally, postmortem analysis confirmed that transplanted AD-MSCs with NapFF-NO hydrogel could ameliorate heart function by promoting angiogenesis and attenuating ventricular remodeling. In conclusion, NapFF-NO hydrogel can obviously improve therapeutic efficacy of AD-MSCs for MI by increasing cell engraftment and angiogenic paracrine action.     

Angiogenesis and hypoxic factors in colorectal cancer

Colorectal cancer is a common cause of cancer death in the developed world. Angiogenesis is a key factor in the growth and dissemination of malignant disease, including colorectal cancer, with significant implications for its clinical management. Over the past few years, significant inroads have been made into understanding the mechanisms and processes of angiogenesis in various malignancies. It is postulated that, with a greater understanding of the angiogenic mechanisms that govern tumor growth, anti-angiogenic compounds may be introduced to combine with conventional means to combat the growth and spread of malignant disease. This review discusses the mechanisms involved in tumor angiogenesis, highlighting its influence in colorectal cancer.     

HESR1基因在血管新生中作用的初步研究

目的研究转录因子HESR1在血管新生中的作用。方法检测内皮细胞激活状态HESR1表达的影响,克隆HESR1基因,转染到HUVEC,绿色荧光和PCR观察HESR1在内皮细胞的表达,流式细胞仪检测它对血管内皮细胞增殖,boyden小室检测对细胞迁移的影响,建体外二维血管模型,观察HESR1对血管形成的影响。结果内皮细胞激活状态HESR1的表达下降,HESR1基因能抑制内皮细胞的增殖和迁移,减少血管新生。结论HESR1基因通过抑制内皮细胞的增殖和迁移,使内皮细胞从激活状态转入安静状态,减少血管的形成,维持血管的稳定状态。     

Spatially Guided Angiogenesis by Three-Dimensional Collagen Scaffolds Micropatterned with Vascular Endothelial Growth Factor

Abstract

Successful regeneration of large and highly functionalized tissue and organs depends on the ability to guide blood vessel formation with three-dimensional scaffolds. Angiogenic growth factors have the potential to stimulate blood vessels in scaffolds. However, simply incorporating angiogenic growth factors in a random fashion may lead to uncontrolled blood vessel generation, which ultimately results in poor blood vessel network function and uneven growth of engineered tissue. To control and guide the formation of a blood vessel network in porous scaffolds, we prepared collagen sponges with micropatterned vascular endothelial growth factor (VEGF). VEGF was micropatterned in three-dimensional collagen sponges using micropatterned collagen/VEGF ice lines, which were prepared by a dispersing machine. The VEGF-micropatterned collagen sponges were implanted subcutaneously in nude mice. Following 6 weeks of implantation, the VEGF-micropatterned collagen sponges induced the formation of micropatterned blood vessel networks. More blood vessels were observed in the regions in which VEGF was immobilized than those without VEGF. The micropattern of VEGF determined the micropattern of the regenerated blood vessel network. The spatial immobilization of VEGF in three-dimensional porous scaffolds may be useful to stimulate guided blood vessel formation in a variety of tissue-engineering applications.     

Promotion of Angiogenesis by Human Endometrial Lymphocytes

The human endometrium is a unique tissue that undergoes dramatic monthly remodeling during the menstrual cycle in preparation for an implanting conceptus. This remodeling involves sequential proliferation and differentiation of endometrial stromal and epithelial cells, coupled with extensive angiogenesis and infiltration of a specific specialized immune cell subset. Increasing evidence points to an essential role for these maternal leukocytes in stimulating the endometrial angiogenesis, and we propose that they also play a key role in the decidual vascular transformation. Aberrant endometrial angiogenesis, decidualisation and vascular transformation is thought to underlie many pathologies of pregnancy, from infertility to the development of preeclampsia and Intra Uterine Growth Restriction. In this chapter we review the cellular processes associated with each stage of endometrial and decidual transformation, detailing the role of the immune cell populations and the angiogenic and chemotactic factors secreted by them.     

Angiogenesis in salivary carcinomas with and without myoepithelial differentiation

To investigate whether salivary carcinomas with and without myoepithelial differentiation could present differences regarding degree of angiogenesis, we compared tumor vascularization between adenoid cystic (31 cases) and epithelial-myoepithelial carcinomas (14) versus mucoepidermoid (37) carcinoma. The expression of peroxiredoxin I was also studied to verify the potential relationship between cellular metabolism and microvascular density. Microvascular density for CD34 and CD105 were significantly lower in carcinomas with myoepithelial differentiation. However, no correlation was found between degree of angiogenesis and amounts of myoepithelial cells. High-grade peroxiredoxin I expression was found in 73.7% of mucoepidermoid carcinomas, whereas 85.1% of carcinomas with myoepithelial differentiation presented low-grade expression. In conclusion, carcinomas with myoepithelial differentiation, regardless of the amounts of myoepithelial cells, are associated to a significantly lower vascular density. The reasons for this lower angiogenic activity remain to be determined but could be related to metabolic characteristics of the cancer cells.     

Angiogenesis and lymphangiogenesis in sporadic hepatic angiomyolipoma

Angiogenesis and lymphangiogenesis are critical processes for tumor growth, invasion, and metastasis. The present study aimed to investigate the distribution and clinical significance of angiogenesis and lymphangiogenesis in hepatic angiomyolipoma (AML). We performed immunohistochemical staining for endothelial cell markers (CD34 and podoplanin) on 80 cases of sporadic hepatic AMLs. Microvessel density (MVD) and lymphatic vessel density (LVD) were determined in intratumoral and peritumoral regions and adjacent non-tumorous liver tissues. All hepatic AMLs showed positive staining for CD34 and podoplanin. Intratumoral and peritumoral MVDs and LVDs were significantly higher than those in adjacent liver tissues (P < 0.001). No statistical difference in both MVD and LVD was found between intratumoral and peritumoral areas. Large tumors (>5 cm) had a significantly increased MVD and LVD as compared with smaller tumors. A significant positive correlation was found between average LVDs and MVDs (r = 0.567, P < 0.001), and LVDs were a relatively lower event as compared with MVDs. Double immunostaining revealed that no neoplastic cells positive for HMB-45, an antibody reacting with melanosome-associated antigen, were concurrently immunoreactive for endothelial cell markers. In conclusion, intratumoral and peritumoral angiogenesis and lymphangiogenesis commonly occur in hepatic AMLs, thus representing potential therapeutic targets for this disease.     

Histological techniques for preservation of alginate bead structural integrity using glycolmethacrylate

Abstract

The applications of alginate as a drug delivery vehicle and 3D cell culture scaffold have become increasingly popular in the fields of biomaterials and tissue engineering. Although histological analysis of intact alginate scaffold and cells is a critical aspect of investigations, the existing methods of histological processing often lead to distortions in the scaffold shape, resulting in poor image quality and misrepresentation of the cellular environment. For this reason, the use of glycol methacrylate (GMA) has been explored as an embedding material of alginate scaffolds for histological analysis of embedded cells. The results of the present study demonstrated that soaking alginate scaffolds in a barium chloride solution prior to fixation in neutral buffered formalin (NBF) was a critical step for maintenance of the structure. By slowly infiltrating the hydrogel matrix with GMA using a commercially available embedding kit, the techniques developed in the present study allowed preservation of alginate bead structural integrity and successful staining of the embedded cells.