Integrin expression and integrin-mediated adhesion in vitro of human multipotent stromal cells (MSCs) to endothelial cells from various blood vessels

2010 ◽  
Vol 341 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Julie A. Semon ◽  
Lauren H. Nagy ◽  
Claire B. Llamas ◽  
H. Alan Tucker ◽  
Ryang Hwa Lee ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Stromal Cells ◽  
Integrin Expression ◽  
Multipotent Stromal Cells

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

scholarly journals Phospholipase Cγ Activation Drives Increased Production of Autotaxin in Endothelial Cells and Lysophosphatidic Acid-Dependent Regression

2010 ◽  
Vol 30 (10) ◽  
pp. 2401-2410 ◽  
Author(s):  
Eunok Im ◽  
Ruta Motiejunaite ◽  
Jorge Aranda ◽  
Eun Young Park ◽  
Lorenzo Federico ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Lysophosphatidic Acid ◽  
Vascular Endothelial ◽  
Additional Mechanism ◽  
Phospholipase Cγ1 ◽  
Common Substrate ◽  
Phosphoinositide 3 Kinase ◽  
Endothelial Growth Factor

ABSTRACT We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase Cγ1 (PLCγ) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism by which PLCγ promoted regression of tubes and blood vessels. Namely, it increased the level of autotaxin (ATX), which is a secreted form of lysophospholipase D that produces lysophosphatidic acid (LPA). LPA promoted motility of endothelial cells, leading to disorganization/regression of tubes in vitro. Furthermore, mice that under- or overexpressed members of this intrinsic destabilization pathway showed either delayed or accelerated, respectively, regression of blood vessels. We conclude that endothelial cells can be instructed to engage a PLCγ-dependent intrinsic destabilization pathway that results in the production of soluble regression factors such as ATX and LPA. These findings are likely to potentiate ongoing efforts to prevent, manage, and eradicate numerous angiogenesis-based diseases such as proliferative diabetic retinopathy and solid tumors.

scholarly journals Human iPSC-derived mesodermal progenitor cells preserve their vasculogenesis potential after extrusion and form hierarchically organized blood vessels

2021 ◽  
Author(s):  
Leyla Dogan ◽  
Ruben Scheuring ◽  
Nicole Wagner ◽  
Yuichiro Ueda ◽  
Philipp Woersdoerfer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Progenitor Cells ◽  
Vessel Wall ◽  
De Novo ◽  
Hierarchical Organization ◽  
Wall Structure ◽  
Electron Microscopic ◽  
Vessel Formation

Post-fabrication formation of a proper vasculature remains an unresolved challenge in bioprinting. Established strategies focus on the supply of the fabricated structure with nutrients and oxygen and either rely on the mere formation of a channel system using fugitive inks, or additionally use mature endothelial cells and/or peri-endothelial cells such as smooth muscle cells for the formation of blood vessels in vitro. Functional vessels, however, exhibit a hierarchical organization and multilayered wall structure that is important for their function. Human induced pluripotent stem cell-derived mesodermal progenitor cells (hiMPCs) have been shown to possess the capacity to form blood vessels in vitro, but have so far not been assessed for their applicability in bioprinting processes. Here, we demonstrate that hiMPCs, after formulation into an alginate/collagen type 1 bioink and subsequent extrusion, retain their ability to give rise to the formation of complex vessels that display a hierarchical network in a process that mimicks the embryonic steps of vessel formation by vasculogenesis. Histological evaluations at different time points of extrusion revealed initial formation of spheres, followed by lumen formation and further structural maturation as evidenced by building a multilayered vessel wall and a vascular network. These findings are supported by immunostainings for endothelial and peri-endothelial cell markers as well as electron microscopic analyses at the ultrastructural level. Moreover, capillary-like vessel structures deposited a basement membrane-like matrix structure at the basal side between the vessel wall and the alginate-collagen matrix. These results evidence the applicability and great potential of hiMPCs for the bioprinting of vascular structures mimicking the basic morphogenetic steps of de novo vessel formation during embryogenesis.

scholarly journals Kisspeptin-10 Inhibits Angiogenesis in Human Placental Vessels ex Vivo and Endothelial Cells in Vitro

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5927-5934 ◽  
Author(s):  
Thayalini Ramaesh ◽  
James J. Logie ◽  
Antonia K. Roseweir ◽  
Robert P. Millar ◽  
Brian R. Walker ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Biologically Active ◽  
Trophoblast Invasion ◽  
In Vitro Assays ◽  
Dependent Manner ◽  
Inhibition Of Proliferation

Recent studies suggest that kisspeptin (a neuropeptide central to the regulation of gonadotrophin secretion) has diverse roles in human physiology, including a putative role in implantation and placental function. Kisspeptin and its receptor are present in human blood vessels, where they mediate vasoconstriction, and kisspeptin is known to inhibit tumor metastasis and trophoblast invasion, both processes involving angiogenesis. We hypothesized that kisspeptin contributes to the regulation of angiogenesis in the reproductive system. The presence of the kisspeptin receptor was confirmed in human placental blood vessels and human umbilical vein endothelial cells (HUVEC) using immunochemistry. The ability of kisspeptin-10 (KP-10) (a shorter biologically active processed peptide) to inhibit angiogenesis was tested in explanted human placental arteries and HUVEC using complementary ex vivo and in vitro assays. KP-10 inhibited new vessel sprouting from placental arteries embedded in Matrigel and tube-like structure formation by HUVEC, in a concentration-dependent manner. KP-10 had no effect on HUVEC viability or apoptosis but induced concentration-dependent inhibition of proliferation and migration. In conclusion, KP-10 has antiangiogenic effects and, given its high expression in the placenta, may contribute to the regulation of angiogenesis in this tissue.

scholarly journals Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates

2020 ◽  
Vol 6 (7) ◽  
pp. eaay2387 ◽  
Author(s):  
J. N. Harvestine ◽  
T. Gonzalez-Fernandez ◽  
A. Sebastian ◽  
N. R. Hum ◽  
D. C. Genetos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Stromal Cells ◽  
Bone Marrow Aspirate ◽  
De Novo ◽  
Trophic Factor ◽  
Calvarial Defect ◽  
Factor Secretion

Cell-derived extracellular matrix (ECM) provides a niche to promote osteogenic differentiation, cell adhesion, survival, and trophic factor secretion. To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), we perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs, respectively. The composition of cells selected from BMA was distinct on each scaffold. Naïve constructs exhibited robust proangiogenic potential in vitro, while preconditioned scaffolds contained more mesenchymal stem/stromal cells (MSCs) and endothelial cells (ECs) and exhibited an osteogenic phenotype. Upon implantation into an orthotopic calvarial defect, BMA-derived ECs were present in vessels in preconditioned implants, resulting in robust perfusion and greater vessel density over the first 14 days compared to naïve implants. After 10 weeks, human ECs and differentiated MSCs were detected in de novo tissues derived from naïve and preconditioned scaffolds. These results demonstrate that bioreactor-based preconditioning augments the bone-forming potential of BMA.

scholarly journals Intra-Vitreal Administration of Microvesicles Derived from Human Adipose-Derived Multipotent Stromal Cells Improves Retinal Functionality in Dogs with Retinal Degeneration

2019 ◽  
Vol 8 (4) ◽  
pp. 510
Author(s):  
Anna Cislo-Pakuluk ◽  
Agnieszka Smieszek ◽  
Natalia Kucharczyk ◽  
Peter G.C. Bedford ◽  
Krzysztof Marycz
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Stromal Cells ◽  
Clinical Studies ◽  
Stress Conditions ◽  
In Vitro Assays ◽  
Multipotent Stromal Cells ◽  
Mitochondrial Potential ◽  
And Oxidative Stress

This study was designed to determine the influence of microvesicles (MVs) derived from multipotent stromal cells isolated from human adipose tissue (hASCs) on retinal functionality in dogs with various types of retinal degeneration. The biological properties of hASC-MVs were first determined using an in vitro model of retinal Muller-like cells (CaMLCs). The in vitro assays included analysis of hASC-MVs influence on cell viability and metabolism. Brain-derived neurotrophic factor (BDNF) expression was also determined. Evaluation of the hASC-MVs was performed under normal and oxidative stress conditions. Preliminary clinical studies were performed on ten dogs with retinal degeneration. The clinical studies included behavioral tests, fundoscopy and electroretinography before and after hASC-MVs intra-vitreal injection. The in vitro study showed that CaMLCs treated with hASC-MVs were characterized by improved viability and mitochondrial potential, both under normal and oxidative stress conditions. Additionally, hASC-MVs under oxidative stress conditions reduced the number of senescence-associated markers, correlating with the increased expression of BDNF. The preliminary clinical study showed that the intra-vitreal administration of hASC-MVs significantly improved the dogs’ general behavior and tracking ability. Furthermore, fundoscopy demonstrated that the retinal blood vessels appeared to be less attenuated, and electroretinography using HMsERG demonstrated an increase in a- and b-wave amplitude after treatment. These results shed promising light on the application of cell-free therapies in veterinary medicine for retinal degenerative disorders treatment.

scholarly journals In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells

2012 ◽  
Vol 12 (1) ◽  
pp. 7 ◽  
Author(s):  
Radhakrishnan Vishnubalaji ◽  
Muthurangan Manikandan ◽  
May Al-Nbaheen ◽  
Balamuthu Kadalmani ◽  
Abdullah Aldahmash ◽  
...  
Keyword(s):  
Human Skin ◽  
Stromal Cells ◽  
Multipotent Stromal Cells ◽  
In Vitro Differentiation

Carrageenan hydrogel as a scaffold for skin-derived multipotent stromal cells delivery

2018 ◽  
Vol 33 (3) ◽  
pp. 422-434 ◽  
Author(s):  
Michele Patricia Rode ◽  
Addeli Bez Batti Angulski ◽  
Felipe Azevedo Gomes ◽  
Maiara Marques da Silva ◽  
Talita da Silva Jeremias ◽  
...  
Keyword(s):  
Human Skin ◽  
Delivery System ◽  
Stromal Cells ◽  
Kappaphycus Alvarezii ◽  
Skin Wound ◽  
Multipotent Stromal Cells ◽  
Skin Wound Healing ◽  
Matrix Deposition ◽  
Initial Recovery

Carrageenan is a thermoreversible polymer of natural origin widely used in food and pharmaceutical industry that presents a glycosaminoglycan-like structure. Herein, we show that kappa-type carrageenan extracted by a semi-refined process from the red seaweed Kappaphycus alvarezii displayed both chemical and structural properties similar to a commercial carrageenan. Moreover, both extracted carrageenan hydrogel and commercial carrageenan hydrogel can serve as a scaffold for in vitro culture of human skin-derived multipotent stromal cells, demonstrating considerable potential as cell-carrier materials for cell delivery in tissue engineering. Skin-derived multipotent stromal cells cultured inside the carrageenan hydrogels showed a round shape morphology and maintained their growth and viability for at least one week in culture. Next, the effect of the extracted carrageenan hydrogel loaded with human skin-derived multipotent stromal cells was evaluated in a mouse model of full-thickness skin wound. Macroscopic and histological analyses revealed some pointed ameliorated features, such as reduced inflammatory process, faster initial recovery of wounded area, and improved extracellular matrix deposition. These results indicate that extracted carrageenan hydrogel can serve as a scaffold for in vitro growth and maintenance of human SD-MSCs, being also able to act as a delivery system of cells to wounded skin. Thus, evaluation of the properties discussed in this study contribute to a further understanding and specificities of the potential use of carrageenan hydrogel as a delivery system for several applications, further to skin wound healing.

scholarly journals Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance

Blood ◽  
1996 ◽  
Vol 87 (10) ◽  
pp. 4204-4213 ◽  
Author(s):  
S Handt ◽  
WG Jerome ◽  
L Tietze ◽  
RR Hantgan
Keyword(s):  
Endothelial Cells ◽  
Blood Vessels ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Time Dependent ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Activator Inhibitor ◽  
Pai 1

Time-dependent thrombolytic resistance is a critical problem in thrombolytic therapy for acute myocardial infarction. Platelets have been regarded as the main source of plasminogen activator inhibitor-1 (PAI-1) found in occlusive platelet-rich clots. However, endothelial cells are also known to influence the fibrinolytic capacity of blood vessels, but their ability to actively mediate time-dependent thrombolytic resistance has not been fully established. We will show that, in vitro, tumor necrosis factor-alpha-stimulated endothelial cells secrete large amounts of PAI-1 over a period of hours, which then binds to fibrin and protects the clot from tissue plasminogen activator- induced fibrinolysis. In vivo, endothelial cells covering atherosclerotic plaques are influenced by cytokines synthesized by plaque cells. Therefore, we propose that continuous activation of endothelial cells in atherosclerotic blood vessels, followed by elevated PAI-1 secretion and storage of active PAI-1 in the fibrin matrix, leads to clot stabilization. This scenario makes endothelial cells a major factor in time-dependent thrombolytic resistance.

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