Induction Of Blood Vessel Formation Research Articles

Self-Assembled DNA Nanocages Promote Cell Migration and Differentiation of Human Umbilical Vein Endothelial Cells.

DNA nanocages have been explored for abilities to influence cellular behavior and functions. Recent times have seen the development of new emergent functionalities of DNA nanodevices as a class of biomaterials with an immense capacity to interface with biological systems and with vast potential in disease diagnosis and therapeutics. Being chemically robust and biocompatible in nature, DNA nanocages have been surface modified and structurally fine-tuned to find emerging applications in the field of stem-cell therapy and tissue regeneration. DNA nanocages can be used for therapeutic angiogenesis that involves the induction of blood vessel formation and can be used to treat ischemic diseases like stroke or heart failure. This work addresses the effect of DNA nanocages' structural topology on their capacity to stimulate endothelial cell angiogenesis. We tested a panel of four DNA nanocage geometries and checked their potential on the differentiation of human umbilical vein endothelial cells (HUVECs). While different DNA nanocage geometries showed successful induction of angiogenesis and cell migration in HUVECs, tetrahedral DNA cages showed the maximum uptake and angiogenesis potential, thus indicating that not only the composition of materials, but also the 3D arrangement of ligands might play role in stimulating angiogenesis.

Wound healing improvement in large animals using an indirect helium plasma treatment

BackgroundTo optimize wound healing, the use of low-temperature atmospheric pressure plasma (ionized gas) has been proposed as an innovative therapeutic method for treating extensive and chronic wound. The aim of this study was to evaluate the specific effects of an indirect helium plasma treatment in a sheep surgical wound model based on clinical, histopathological and molecular analyses. This study was part of a larger study aimed at assessing five different wound healing improvement methods. MethodsSix sheep were used in this study. Six square wounds were performed on the back of each sheep. Five of the lesions were used to analyze the effect of five different treatments, one of which was the plasma treatment. The sixth lesions was used as control. A 2-min plasma treatment was daily performed, using a radiofrequency helium plasma source for indirect treatments, until complete wound healing was obtained. Biopsies were performed at two and six weeks. The plasma effects were tested through clinical evaluation, histopathological and immunohistological evaluation, real time PCR analysis, bacteriological evaluation and intracellular ROS evaluation. ResultsWound closure time for the plasma-treated wounds was quicker than that of the control group. Plasma treatment drastically reduced the bacterial load in the wounds. A strong increase in intracellular ROS was observed. After six weeks, the inflammatory process was significantly reduced in the plasma-treated case with respect to the control. The plasma treatment was found to lead to an anticipated induction of blood vessel formation, as detected through mRNA expression of VEGF. The high Ki67-positivity at two weeks indicated a strong stimulation of cell proliferation induced by the plasma treatment. The expression of the hair keratine (hKER) at six weeks indicated that the plasma was promoting hair regrowth. The plasma treatment induced an increased rate of reformation of cutaneous adnexa at six weeks. ConclusionsThe obtained results suggest that the plasma action, at the used dose, induces an increase in cell proliferation, a reduction of inflammation, a reduction of the bacterial load, a stimulation of blood vessel formation, and an improvement in the formation of cutaneous adnexa with a positive consequence on hair regrowth.

Celecoxib Nanoparticles for Therapeutic Angiogenesis

Controllable induction of blood vessel formation (angiogenesis) presents an important therapeutic goal in ischemic diseases and is also beneficial in various normal physiological processes. In this study, we have shown that nanoparticles of celecoxib, a lipophilic nonsteroidal anti-inflammatory drug, effectively evoke therapeutic angiogenesis in animal models, in both normal and ischemic organs. Celecoxib is widely considered to inhibit angiogenesis, although a recent study suggests that it can instead promote blood vessel growth in cancer cell lines. The hydrophobic nature of this drug necessitates its administration in nanoparticulate form in order to elicit a perceivable pharmacological response. We developed a facile method for nanoparticle formation by solvent extraction from microemulsions in supercritical carbon dioxide. This method exploits a spontaneous formation of nanometric domains within the microemulsion system and their rapid conversion to nanoparticles by supercritical fluid. The resultant nanoparticles were administered subcutaneously to mice in a biocompatible hydrogel, and caused a 4-fold increase in blood vessel count in normally perfused skin compared with drug-free particles. They were at least as effective in inducing angiogenesis as nanoparticles of deferoxamine, a well-established neovascularization promoter. Next, we evaluated their effect on ischemic tissues in murine model of myocardial infarction. We found that celecoxib nanoparticles were able to induce a significant vascularization of ischemic myocardium and hamper the progression of heart failure, which points toward a new approach for treating ischemia.

Spatiotemporal proliferation of human stromal cells adjusts to nutrient availability and leads to stanniocalcin-1 expression in vitro and in vivo

Cells and tissues are intrinsically adapted to molecular gradients and use them to maintain or change their activity. The effect of such gradients is particularly important for cell populations that have an intrinsic capacity to differentiate into multiple cell lineages, such as bone marrow derived mesenchymal stromal cells (MSCs). Our results showed that nutrient gradients prompt the spatiotemporal organization of MSCs in 3D culture. Cells adapted to their 3D environment without significant cell death or cell differentiation. Kinetics data and whole-genome gene expression analysis suggest that a low proliferation activity phenotype predominates in stromal cells cultured in 3D, likely due to increasing nutrient limitation. These differences implied that despite similar surface areas available for cell attachment, higher cell concentrations in 3D reduced MSCs proliferation, while activating hypoxia related-pathways. To further understand the in vivo effects of both proliferation and cell concentrations, we increased cell concentrations in small (1.8 μl) implantable wells. We found that MSCs accumulation and conditioning by nutrient competition in small volumes leads to an ideal threshold of cell-concentration for the induction of blood vessel formation, possibly signaled by the hypoxia-related stanniocalcin-1 gene.

Suppression of growth and cancer‐induced angiogenesis of aggressive human breast cancer cells (MDA‐MB‐231) on the chorioallantoic membrane of developing chicken embryos by E‐peptide of pro‐IGF‐I

E-peptide of the pro-Insulin-like growth factor-I (pro-IGF-I) is produced from pre-pro-IGF-I by proteolytic cleavage in the post-translational processing. Previous in vitro studies conducted in our laboratory showed that Ea4-peptide of rainbow trout (rt) pro-IGF-I or Eb-peptide of human (h) pro-IGF-I exhibited activities including induction of morphological differentiation, inhibition of anchorage-independent cell growth and suppression of invasion of several well established human cancer cell lines such as MDA-MB-231, HT-29, SK-N-F1, and HepG-2 (Chen et al. [2002] Gen Comp Endocrinol 126:342-351; Kuo and Chen [2002] Exp Cell Res 280:75-89). Seeding of aggressive human breast cancer cells, MDA-MB-231, on the chorioallantoic membrane (CAM) of 5 days old chicken embryos resulted in rapid growth and invasion of the cells and induction of blood vessel formation around the MDA-MB-231 cell mass in the chicken embryos. The invasion of MDA-MB-231 cells in the chicken embryos was further confirmed by immunocytochemistry. The rapid growth and invasion of MDA-MB-231 cells and the induction of blood vessel formation by MDA-MB-231 cells on chicken CAM are inhibited by treatment with a single or multiple doses of rtEa4- or hEb-peptide. Furthermore, a dose-dependent inhibition of angiogenesis by rtEa4- or hEb-peptide was also demonstrated by the chicken CAM assay. Results of microarray analysis of human gene chips (containing 9,500 unique cDNA clones) and confirmation by comparative real-time RT-PCR analysis showed that a group of genes related to cancer cell activities are up- or down-regulated in MDA-MB-231 cells transfected with a rtEa4-peptide gene. Together these results confirm the anti-tumor activity of rtEa4- and hEb-peptides, and further suggest that these peptides could be developed as therapeutics for treating human cancers.