Differences in human placental mesenchymal stromal cells may impair vascular function in FGR

Reproduction ◽  
2021 ◽  
Author(s):  
Anna L Boss ◽  
Lawrence W Chamley ◽  
Anna E.s Brooks ◽  
Joanna L James
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Hyaluronan Synthase ◽  
Perivascular Niche ◽  
Affymetrix Microarrays ◽  
Formation Function ◽  
Hyaluronan Synthase 2 ◽  
And Control

Placentae from pregnancies with fetal growth restriction (FGR) exhibit poor oxygen and nutrient exchange, in part due to impaired placental vascular development. Placental mesenchymal stromal cells (pMSCs) reside in a perivascular niche, where they may influence blood vessel formation/ function. However, the role of pMSCs in vascular dysfunction in FGR is unclear. To elucidate the mechanisms by which pMSCs may impact placental vascularisation we compared the transcriptomes of human pMSCs isolated from FGR (<5th centile) (n=7) and gestation-matched control placentae (n=9) using Affymetrix microarrays. At the transcriptome level there were no statistically significant differences between normal and FGR pMSCs, however several genes linked to vascular function exhibited notable fold changes, and thus the dataset was used as a hypothesis-generating tool for possible dysfunction in FGR. Genes/proteins of interest were followed up by real-time PCR and by immunohistochemistry. Gene expression of ADAMTS1 and FBLN2 (fibulin-2) were significantly upregulated, whilst HAS2 (hyaluronan synthase-2) was significantly downregulated, in pMSCs from FGR placentae (n=8) relative to controls (n=7, p<0.05 for all). At the protein level, significant differences in the level of fibulin-2 and hyaluronan synthase-2, but not ADAMTS1 were confirmed between pMSCs from FGR and control pregnancies by western blot. All three proteins demonstrated perivascular expression in third-trimester placentae. Fibulin-2 maintains vessel elasticity, and its increased expression in FGR pMSCs could help explain the increased distensibility of FGR blood vessels. ADAMTS1 and hyaluronan synthase-2 regulate angiogenesis, and their differential expression by FGR pMSCs may contribute to the impaired angiogenesis in these placentae.

Abstract TP265: Microparticles Play A Role In Mediating Angiogenic Effect Of Mesenchymal Stromal Cells On Cerebral Vascular Endothelial Cells

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ji Chen ◽  
Xiang Xiao ◽  
Cheng Zhang ◽  
Shuzhen Chen ◽  
Jianying Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Culture Medium ◽  
Cell Function ◽  
Angiogenic Factors ◽  
Pcr Analysis ◽  
Angiogenic Effect ◽  
And Control

Microparticles (MPs) represent a novel network for intercellular communication. Our previous works found that MPs from db/db diabetic mice impaired endothelial progenitor cell function. This study investigated the role of MPs from mesenchymal stromal cells (MSCs) in regulating cerebrovascular endothelial cell (cEC) function and gene expression. Male C57BL/6 mice and green fluorescent protein (GFP)-transgenic mice were used for cEC and MSC donors, respectively. The cECs were cultured on 6-well plates and MSCs were seeded on well inserts with a 0.4 μm pore sized filter for co-culture for 3 days before various measurements. MSC conditional medium (MSC-CM) was used for producing MPs and MSC-CM deprived of MPs (MSC-CM-dMP) by centrifuge. MPs deprived of mRNAs and miRNAs (MSC-MP-dRNA) were prepared by treating with RNAse. In some experiments, cECs were incubated with normal culture medium (control), MSC-CM, MSC-CM-dMP, MSC-MPs or MSC-MP-dRNA for 3 days. After different treatments, the cECs were used for confocal microscopy analysis of GFP level, real-time PCR analysis of angiogenic gene expression and functional analyses. The levels of angiogenic factors were measured by ELISA method. Results showed: 1) GFP-MPs were appeared in cEC culture medium, and GFP was detected in cECs after co-culture with MSCs; 2) Co-culture with MSCs or culture with MSC-CM significantly upregulated mRNA expression of VEGFR2 and CXCR4 in cECs and increased the angiogenic factors (VEGF and SDF-1) in culture supernatant; 3) Co-culture with MSCs or culture with MSC-CM increased cEC function (migration: 68.6 ± 3.2, 66.8 ± 2.6 and 48.8 ± 2.6 tubes/field for MSC, MSC-CM and control, respectively; tube formation: 52.8 ± 2.6, 48.8 ± 2.0 and 32.6 ± 1.2 tubes/field for MSC, MSC-CM and control, respectively; n=5/group, P <0.05 or 0.01, vs. control); 4) Whereas, incubation with MSC-CM-dMP or MSC-MP-dRNA aborted the effect on mRNA expression, and reduced the functional effects by about 50%. In conclusion, MPs mediate angiogenic effect of MSCs on cECs via RNA and/or protein deliveries, which represent a novel mechanism of cell communication, providing a potential therapeutic target for endothelial dysfunction and cerebrovascular diseases.

Photoencapsulated-mesenchymal stromal cells in biodegradable thiol-acrylate hydrogels enhance regeneration of craniofacial bone tissue defects

2020 ◽  
Vol 15 (9) ◽  
pp. 2115-2127
Author(s):  
Arbi Aghali ◽  
Huseyin E Arman
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cranial Bone ◽  
Activity Levels ◽  
Glycol Diacrylate ◽  
Hydrogel Scaffolds ◽  
Poly Ethylene ◽  
And Control ◽  
Cell Carriers

Aim: This study investigated biodegradable thiol-acrylate hydrogels as stem cell carriers to facilitate cranial bone regeneration. Materials & methods: Two formulations of thiol-acrylate hydrogels (5 and 15 wt% Poly[ethylene glycol]-diacrylate [PEGDA] hydrogels) were used as stem cell carriers. Bone marrow mesenchymal stromal cells and dental pulp mesenchymal stromal cells were photoencapsulated and cultured in basal or osteogenic medium 3 days before the surgery. Using New Zealand White Rabbits, four defects (5 mm diameter and 2 mm thickness) were created and hydrogel scaffolds were implanted in each rabbit cranium for 6 weeks. Results & Conclusion: AlamarBlue assay showed increasing metabolic activity levels in 5 wt% PEGDA hydrogels than 15 wt% PEGDA hydrogels. Photoencapsulated-mesenchymal stromal cells in 15 wt% PEGDA hydrogels demonstrated significantly increasing alkaline phosphatase activity levels on day 7 compared with days 1 and 3. Histological diagnosis showed 5 wt% PEGDA hydrogels resulted in lower averaged residual gel areas than 15 wt% PEGDA hydrogel specimens and control groups 6 weeks postimplantation.

scholarly journals The Metastatic Bone Marrow Niche in Neuroblastoma: Altered Phenotype and Function of Mesenchymal Stromal Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3231 ◽  
Author(s):  
Caroline Hochheuser ◽  
Lieke M. J. van Zogchel ◽  
Marion Kleijer ◽  
Carlijn Kuijk ◽  
Simon Tol ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bone Marrow Niche ◽  
Main Site ◽  
Bm Niche ◽  
Promote Tumor Cell ◽  
And Function ◽  
And Control

Background: The bone marrow (BM) is the main site of metastases and relapse in patients with neuroblastoma (NB). BM-residing mesenchymal stromal cells (MSCs) were shown to promote tumor cell survival and chemoresistance. Here we characterize the MSC compartment of the metastatic NB BM niche. Methods: Fresh BM of 62 NB patients (all stages), and control fetal and adult BM were studied by flow cytometry using well-established MSC-markers (CD34−, CD45−, CD90+, CD105+), and CD146 and CD271 subtype-markers. FACS-sorted BM MSCs and tumor cells were validated by qPCR. Moreover, isolated MSCs were tested for multilineage differentiation and Colony-forming-unit-fibroblasts (CFU-Fs) capacity. Results: Metastatic BM contains a higher number of MSCs (p < 0.05) with increased differentiation capacity towards the osteoblast lineage. Diagnostic BM contains a MSC-subtype (CD146+CD271−), only detected in BM of patients with metastatic-NB, determined by flow cytometry. FACS-sorting clearly discriminated MSC(-subtypes) and NB fractions, validated by mRNA and DNA qPCR. Overall, the CD146+CD271− subtype decreased during therapy and was detected again in the majority of patients at relapse. Conclusions: We demonstrate that the neuroblastoma BM-MSC compartment is different in quantity and functionality and contains a metastatic-niche-specific MSC-subtype. Ultimately, the MSCs contribution to tumor progression could provide targets with potential for eradicating resistant metastatic disease.

scholarly journals Mesenchymal Stromal Cells Prevent Allostimulation In Vivo and Control Checkpoints of Th1 Priming: Migration of Human DC to Lymph Nodes and NK Cell Activation

Stem Cells ◽  
2015 ◽  
Vol 33 (10) ◽  
pp. 3087-3099 ◽  
Author(s):  
C. Consentius ◽  
L. Akyüz ◽  
J. A. Schmidt-Lucke ◽  
C. Tschöpe ◽  
L. Pinzur ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Activation ◽  
Nk Cell ◽  
And Control

scholarly journals The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 431 ◽  
Author(s):  
Zyrafete Kuҫi ◽  
Christiane Jordan ◽  
Sibylle Wehner ◽  
Jan Sörensen ◽  
Andrea Jarisch ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Functional Activity ◽  
Thalassemia Major ◽  
Control Group ◽  
Hematological Diseases ◽  
Cell Based Therapy ◽  
Healthy Donors ◽  
And Control

As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 × 106 BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors’ MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors’ MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.

scholarly journals Blunted peripheral but not cerebral vasodilator function in young otherwise healthy adults with persistent symptoms following COVID-19

2021 ◽  
Author(s):  
Damsara Nandadeva ◽  
Benjamin E. Young ◽  
Brandi Y. Stephens ◽  
Ann-Katrin Grotle ◽  
Rachel J. Skow ◽  
...  
Keyword(s):  
Young Adults ◽  
Arterial Stiffness ◽  
Acute Phase ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Reactive Hyperemia ◽  
Healthy Adults ◽  
Persistent Symptoms ◽  
And Control ◽  
Cerebral Vasodilator

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral (brachial artery flow-mediated dilation (FMD) and reactive hyperemia) and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 weeks past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight COVID subjects were symptomatic (SYM) and 8 were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and Control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared to ASYM (6.8 ± 0.9%; P = 0.007) and Control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and Control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared to ASYM (64 ± 19 cm/s; P = 0.025) and Control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macro- and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared to controls who never had COVID.

Current Status of Myocardial Restoration via the Paracrine Function of Mesenchymal Stromal Cells

2021 ◽  
Author(s):  
Michael Nguyen-Truong ◽  
Peiman Hematti ◽  
Zhijie Wang
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mechanisms Of Action ◽  
Current Status ◽  
Preclinical Studies ◽  
Regenerative Therapy ◽  
Future Directions ◽  
Advantages And Disadvantages ◽  
Therapeutic Outcomes ◽  
And Control

Mesenchymal stromal cells (MSCs) have been studied for nearly two decades as a therapy for myocardial restoration. An emerging direction to repair myocardium is through their paracrine function, which includes the utilization of MSC-derived conditioned medium or extracellular vesicles. In this review, we go over the unique characteristics of MSCs that make it suitable for 'off-the-shelf', cell-free regenerative therapy, current MSC-derived cell-free approaches including their advantages and disadvantages, and the known mechanisms of action of the paracrine effect of MSCs. With a summary of the clinical trials and preclinical studies of MSC-derived cell-free therapy, we classify the aforementioned mechanisms into angiogenesis, immunomodulation, collagen regulation, anti-apoptosis, and anti-oxidation. Particularly, we discuss on ways researchers have worked towards enhancing these desired properties to improve the therapeutic outcomes and the investigation of mechanobiology involved in MSC paracrine function. Lastly, we bring up the remaining challenges in this arising field and suggestions for future directions to improve our understanding and control over the potential of MSC paracrine function for myocardial restoration.

scholarly journals Effect of chronic and selective endothelin receptor antagonism on microvascular function in Type 2 diabetes

2008 ◽  
Vol 294 (6) ◽  
pp. H2743-H2749 ◽  
Author(s):  
Kamakshi Sachidanandam ◽  
Mostafa M. Elgebaly ◽  
Alex K. Harris ◽  
Jim R. Hutchinson ◽  
Erin M. Mezzetti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Receptor Antagonism ◽  
Potent Vasoconstrictor ◽  
The Individual ◽  
The Right ◽  
And Control

Vascular dysfunction, which presents either as an increased response to vasoconstrictors or an impaired relaxation to dilator agents, results in worsened cardiovascular outcomes in diabetes. We have established that the mesenteric circulation in Type 2 diabetes is hyperreactive to the potent vasoconstrictor endothelin-1 (ET-1) and displays increased nitric oxide-dependent vasodilation. The current study examined the individual and/or the relative roles of the ET receptors governing vascular function in the Goto-Kakizaki rat, a mildly hyperglycemic, normotensive, and nonobese model of Type 2 diabetes. Diabetic and control rats received an antagonist to either the ET type A (ETA; atrasentan; 5 mg·kg−1·day−1) or type B (ETB; A-192621; 15 or 30 mg·kg−1·day−1) receptors for 4 wk. Third-order mesenteric arteries were isolated, and vascular function was assessed with a wire myograph. Maximum response to ET-1 was increased in diabetes and attenuated by ETA antagonism. ETB blockade with 15 mg/kg A-192621 augmented vasoconstriction in controls, whereas it had no further effect on ET-1 hyperreactivity in diabetes. The higher dose of A-192621 showed an ETA-like effect and decreased vasoconstriction in diabetes. Maximum relaxation to acetylcholine (ACh) was similar across groups and treatments. ETB antagonism at either dose had no effect on vasorelaxation in control rats, whereas in diabetes the dose-response curve to ACh was shifted to the right, indicating a decreased relaxation at 15 mg/kg A-192621. These results suggest that ETA receptor blockade attenuates vascular dysfunction and that ETB receptor antagonism exhibits differential effects depending on the dose of the antagonists and the disease state.

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