scholarly journals Chemically induced hypoxia by dimethyloxalylglycine (DMOG)-loaded nanoporous silica nanoparticles supports endothelial tube formation by sustained VEGF release from adipose tissue-derived stem cells

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Sarah Zippusch ◽  
Karen F W Besecke ◽  
Florian Helms ◽  
Melanie Klingenberg ◽  
Anne Lyons ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Silica Nanoparticles ◽  
Umbilical Vein ◽  
Mesoporous Silica Nanoparticles ◽  
Tube Formation ◽  
Tube Length ◽  
Nanoporous Silica ◽  
Promising Tool ◽  
Endothelial Tube Formation

Abstract Inadequate vascularization leading to insufficient oxygen and nutrient supply in deeper layers of bioartificial tissues remains a limitation in current tissue engineering approaches to which pre-vascularization offers a promising solution. Hypoxia triggering pre-vascularization by enhanced vascular endothelial growth factor (VEGF) expression can be induced chemically by dimethyloxalylglycine (DMOG). Nanoporous silica nanoparticles (NPSNPs, or mesoporous silica nanoparticles, MSNs) enable sustained delivery of molecules and potentially release DMOG allowing a durable capillarization of a construct. Here we evaluated the effects of soluble DMOG and DMOG-loaded NPSNPs on VEGF secretion of adipose tissue-derived stem cells (ASC) and on tube formation by human umbilical vein endothelial cells (HUVEC)-ASC co-cultures. Repeated doses of 100 µM and 500 µM soluble DMOG on ASC resulted in 3- to 7-fold increased VEGF levels on day 9 (P < 0.0001). Same doses of DMOG-NPSNPs enhanced VEGF secretion 7.7-fold (P < 0.0001) which could be maintained until day 12 with 500 µM DMOG-NPSNPs. In fibrin-based tube formation assays, 100 µM DMOG-NPSNPs had inhibitory effects whereas 50 µM significantly increased tube length, area and number of junctions transiently for 4 days. Thus, DMOG-NPSNPs supported endothelial tube formation by upregulated VEGF secretion from ASC and thus display a promising tool for pre-vascularization of tissue-engineered constructs. Further studies will evaluate their effect in hydrogels under perfusion.

scholarly journals Different Angiogenic Potentials of Mesenchymal Stem Cells Derived from Umbilical Artery, Umbilical Vein, and Wharton’s Jelly

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Lu Xu ◽  
Jianjun Zhou ◽  
Jingyu Liu ◽  
Yong Liu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Wharton’S Jelly ◽  
Tube Length ◽  
Branch Points ◽  
Differentiation Potential ◽  
Wharton's Jelly ◽  
Allogeneic Cell Therapy ◽  
Perivascular Stem Cells

Human mesenchymal stem cells derived from the umbilical cord (UC) are a favorable source for allogeneic cell therapy. Here, we successfully isolated the stem cells derived from three different compartments of the human UC, including perivascular stem cells derived from umbilical arteries (UCA-PSCs), perivascular stem cells derived from umbilical vein (UCV-PSCs), and mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs). These cells had the similar phenotype and differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. However, UCA-PSCs and UCV-PSCs had more CD146+ cells than WJ-MSCs (P<0.05). Tube formation assay in vitro showed the largest number of tube-like structures and branch points in UCA-PSCs among the three stem cells. Additionally, the total tube length in UCA-PSCs and UCV-PSCs was significantly longer than in WJ-MSCs (P<0.01). Microarray, qRT-PCR, and Western blot analysis showed that UCA-PSCs had the highest expression of the Notch ligand Jagged1 (JAG1), which is crucial for blood vessel maturation. Knockdown of Jagged1 significantly impaired the angiogenesis in UCA-PSCs. In summary, UCA-PSCs are promising cell populations for clinical use in ischemic diseases.

scholarly journals miRNA-24 Down-Regulates Endothelial Nitric Oxide Synthase Expression and Inhibits Endothelial Cell Tube Formation

2020 ◽  
Author(s):  
Xuelan Luo ◽  
Wei Chen ◽  
Yuwang Qin ◽  
Na Gan ◽  
Dongning Lvy ◽  
...  
Keyword(s):  
Umbilical Vein ◽  
Cell Number ◽  
Tube Formation ◽  
High Expression ◽  
Luciferase Reporter ◽  
Tube Length ◽  
Control Group ◽  
Reporter System ◽  
Enos Expression ◽  
High Expression Group

Abstract Background: This study is to investigate the effects of miR-24 on expression of eNOS and Sp1, the proliferation, migration, and tube formation abilities of human umbilical vein endothelial cells (HUVECs). Results: After transfection with miR-24 overexpression plasmid or anti-miR-24, miR-24 was successfully over-expressed or inhibited. Compared with the control group, the HUVEC proliferation and cell number in the miR-24 high expression group was significantly decreased. Moreover, for the miR-24 high expression group, the cell motility was slower, and the migrating cells were significantly decreased by 61.20%, with very few capillaries in the Matrigel assay. Furthermore, the mRNA and protein expression levels of eNOS were decreased by 44.44% and 47.00 %, respectively. Meanwhile, the mRNA and protein levels of Sp1 were significantly decreased by 34.88% and 68.00%, respectively. In the miR-24 interference group, the above indexes were decreased compared with control group, while significantly increased compared with the miR-24 high expression group, especially concerning the number of branches and the tube length. Moreover, the Sp-1 and eNOS mRNAs were found to be the direct targets of miR-24 by a luciferase reporter system.Conclusion: Over-expression of miR-24 significantly suppresses cell proliferation, migration, and tube formation ability of HUVECs, via regulating eNOS expression. The transcription factor Sp1, a target of miR-24, might contribute to the eNOS expression regulation and the inhibiting effects on HUVECs.

scholarly journals Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Izuagie Attairu Ikhapoh ◽  
Christopher J. Pelham ◽  
Devendra K. Agrawal
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Tube Formation ◽  
Ang Ii ◽  
Induced Differentiation ◽  
Endothelial Tube Formation ◽  
Marker Expression

Coronary artery stenting or angioplasty procedures frequently result in long-term endothelial dysfunction or loss and complications including arterial thrombosis and myocardial infarction. Stem cell-based therapies have been proposed to support endothelial regeneration. Mesenchymal stem cells (MSCs) differentiate into endothelial cells (ECs) in the presence of VEGF-Ain vitro. Application of VEGF-A and MSC-derived ECs at the interventional site is a complex clinical challenge. In this study, we examined the effect of atherogenic cytokines (IL-6, TNFα, and Ang II) on EC differentiation and function. MSCs (CD44+, CD73+, CD90+, CD14−, and CD45−) were isolated from the bone marrow of Yucatan microswine. Naïve MSCs cultured in differentiation media containing VEGF-A (50 ng/mL) demonstrated increased expression of EC-specific markers (vWF, PECAM-1, and VE-cadherin), VEGFR-2 and Sox18, and enhanced endothelial tube formation. IL-6 or TNFαcaused a dose-dependent attenuation of EC marker expression in VEGF-A-stimulated MSCs. In contrast, Ang II enhanced EC marker expression in VEGF-A-stimulated MSCs. Addition of Ang II to VEGF-A and IL-6 or TNFαwas sufficient to rescue the EC phenotype. Thus, Ang II promotes but IL-6 and TNFαinhibit VEGF-A-induced differentiation of MSCs into ECs. These findings have important clinical implications for therapies intended to increase cardiac vascularity and reendothelialize coronary arteries following intervention.

scholarly journals Multi-Parametric Profiling of Endothelial Cell Networks Reveals Functional Role of Glutamate Receptors in Angiogenesis

2019 ◽  
Author(s):  
Heba Z. Sailem ◽  
Ayman Al Haj Zen
Keyword(s):  
Glutamate Receptors ◽  
High Throughput Screening ◽  
Network Formation ◽  
Meta Analysis ◽  
Network Connectivity ◽  
Tube Formation ◽  
Tube Length ◽  
Endothelial Tube Formation ◽  
Branching Points ◽  
Similar Phenotype

AbstractAngiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer’s disease. High throughput screening of endothelial tube formation provides a robust approach for identifying drugs that impact microvascular network formation and morphology. However, the analysis of resulting imaging datasets has been limited to a few phenotypic features such as the total tube length or the number of branching points. Here we developed a high content analysis framework for detailed quantification of various aspects of network morphology including network complexity, symmetry and topology. By applying our approach to a high content screen of 1,280 drugs, we found that many drugs that result in a similar phenotype share the same mechanism of action or common downstream signalling pathways. Our multiparametric analysis revealed a group of drugs, that target glutamate receptors, results in enhanced branching and network connectivity. Using an integrative meta-analysis approach, we validated the link between these receptors and angiogenesis. We further found that the expression of these genes correlates with the prognosis of Alzheimer’s patients. In conclusion, our work shows that detailed image analysis of complex endothelial phenotypes can reveal new insights into biological mechanisms modulating the morphogenesis of endothelial networks and identify potential therapeutics for angiogenesis-related diseases.

Multifunctional Mesoporous Silica Nanoparticles for Cancer Therapy and Imaging

2019 ◽  
Vol 26 (31) ◽  
pp. 5745-5763 ◽  
Author(s):  
Fahima Dilnawaz
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Cancer Therapy ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Structural Characteristics ◽  
Mesoporous Silica Nanoparticles ◽  
Synthetic Methods ◽  
Promising Tool ◽  
Stimuli Response

Background: Cancer is a widespread disease and has a high mortality rate. Popular conventional treatment encompasses chemotherapy, radiation and surgical resection. However, these treatments impart lots of toxicity problems to the patients mostly due to their non-selectiveness nature, which invokes drug resistances and severe side-effects. Objectives: In this regard, nanotechnology has claimed to be a smart technology that provides the system with the ability to target drugs to the specific sites. With the use of nanotechnology, various nanomaterials that are widely used as a drug delivery vehicle are created for biomedical applications. Amongst variously diversified nanovehicles, mesoporous silica nanoparticles (MSNs) have attracted enormous attention due to their structural characteristics, great surface areas, tunable pore diameters, good thermal and chemical stability, excellent biocompatibility along with ease of surface modification. Furthermore, the drug release from MSNs can be tailored through various stimuli response gatekeeper systems. The ordered structure of MSNs is extremely suitable for loading of the high amount of drug molecules with controlled delivery for targeting the cancer tissues via enhanced permeability and retention effect or further with surface modification, it can also be actively targeted by various ligands. Methods: The review article emphases the common synthetic methods and current advancement of MSNs usages for stimuli response drug delivery, immunotherapy as well as the theranostic ability for cancer. Conclusion: Although MSNs are becoming the promising tool for more efficient and safer cancer therapy, however, additional translational studies are required to explore its multifunctional ability in a clinical setting.

Comparison of in Vitro Vasculogenesis Potential between ASCs with BM-MSCs

2021 ◽  
Vol 11 (5) ◽  
pp. 362-378
Author(s):  
Ani Oranda Panjaitan ◽  
Dewi Sukmawati ◽  
Ria Anggraeni
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tube Formation ◽  
Tube Length ◽  
Branch Points ◽  
Marrow Mesenchymal Stem Cells ◽  
Cd34 Expression

Tube formation assay is the most widely used method as a vasculogenesis/ angiogenesis test in vitro. Mesenchymal stem cells (MSCs) are multipotent adult cells. The paracrine effect of MSCs on neovascularization is well known. In general, MSCs do not express CD34 hematopoietic surface marker, but according to some experts, bone marrow mesenchymal stem cells (BM-MSCs) express CD34 in vivo and lose their expression when they are cultured in vitro, while adipose-derived stem cells (ASCs) still have CD34 expression in the early passages when cultured in vitro. BM-MSCs are the most widely used MSC, but ASCs are also used in stem cell therapy and tissue engineering for angiogenesis purposes. Until now, the potential of vasculogenesis between ASCs and BM-MSCs is still unclear. Expression of CD34 is also unknown whether affecting the quality of tube formation. This study wanted to compare the potential of vasculogenesis between ASC and BM-MSCs through tube formation test and CD34 expression.Measurements of vasculogenesis quality showed higher tube length, number of loopsand mean number of branch points on BM-MSC. Both BM-MSCs and ASCs showed low CD34 levels.BM-MSCs showed better tube formation ability compared with ASCs. No association was found between CD34 levels and MSC vasculogenesis capability. Key words: ASCs, BM-MSCs, CD34, matrigel, tube formation.

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