scholarly journals Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Kapka Miteva ◽  
Sophie Van Linthout ◽  
Hans-Dieter Volk ◽  
Carsten Tschöpe
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Left Ventricular ◽  
Inflammatory Cardiomyopathy ◽  
Long Term Outcomes ◽  
Paracrine Effects ◽  
Cellular Transplantation ◽  
The Impact

Myocarditis is a common inflammatory cardiomyopathy, associated with cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction. Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. Experimental and clinical studies consistently support the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct paracrine effects supporting endogenous regeneration, but most important are their remarkable immunoregulatory properties. In this review, an overview of current knowledge on immunopathology in myocarditis will be given. Furthermore, current research regarding the immunomodulatory properties of MSCs in the context of myocarditis will be discussed. Finally, the impact of MSC priming by the environment on their functionality and the advantages of systemic administration of MSCs under myocarditis are outlined.

scholarly journals Impact of Syndecan-2-Selected Mesenchymal Stromal Cells on the Early Onset of Diabetic Cardiomyopathy in Diabetic db/db Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Kathleen Pappritz ◽  
Fengquan Dong ◽  
Kapka Miteva ◽  
Arpad Kovacs ◽  
Muhammad El-Shafeey ◽  
...  
Keyword(s):  
Experimental Model ◽  
Mesenchymal Stromal Cells ◽  
Diabetic Cardiomyopathy ◽  
Stromal Cells ◽  
Early Onset ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
Lv Function ◽  
Protein Distribution ◽  
The Impact

Background: Mesenchymal stromal cells (MSCs) are an attractive cell type for cell therapy given their immunomodulatory, anti-fibrotic, and endothelial-protective features. The heparin sulfate proteoglycan, syndecan-2/CD362, has been identified as a functional marker for MSC isolation, allowing one to obtain a homogeneous cell product that meets regulatory requirements for clinical use. We previously assessed the impact of wild-type (WT), CD362−, and CD362+ MSCs on local changes in protein distribution in left ventricular (LV) tissue and on LV function in an experimental model of early-onset diabetic cardiomyopathy. The present study aimed to further explore their impact on mechanisms underlying diastolic dysfunction in this model.Materials: For this purpose, 1 × 106 WT, CD362−, or CD362+ MSCs were intravenously (i.v.) injected into 20-week-old diabetic BKS.Cg-m+/+Leprdb/BomTac, i.e., db/db mice. Control animals (db+/db) were injected with the equivalent volume of phosphate-buffered saline (PBS) alone. After 4 weeks, mice were sacrificed for further analysis.Results: Treatment with all three MSC populations had no impact on blood glucose levels in db/db mice. WT, CD362−, and CD362+ MSC application restored LV nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels in db/db mice, which correlated with a reduction in cardiomyocyte stiffness. Furthermore, all stromal cells were able to increase arteriole density in db/db mice. The effect of CD362+ MSCs on NO and cGMP levels, cardiomyocyte stiffness, and arteriole density was less pronounced than in mice treated with WT or CD362− MSCs. Analysis of collagen I and III protein expression revealed that fibrosis had not yet developed at this stage of experimental diabetic cardiomyopathy. All MSCs reduced the number of cardiac CD3+ and CD68+ cells in db/db mice, whereas only splenocytes from CD362−- and CD362+-db/db mice exhibited a lower pro-fibrotic potential compared to splenocytes from db/db mice.Conclusion: CD362+ MSC application decreased cardiomyocyte stiffness, increased myocardial NO and cGMP levels, and increased arteriole density, although to a lesser extent than WT and CD362− MSCs in an experimental model of early-onset diabetic cardiomyopathy without cardiac fibrosis. These findings suggest that the degree in improvement of cardiomyocyte stiffness following CD362+ MSC application was insufficient to improve diastolic function.

scholarly journals The Effects of Hypoxia on the Immune-Modulatory Properties of Bone Marrow-Derived Mesenchymal Stromal Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zsolt Fábián
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cellular Therapy ◽  
Current Knowledge ◽  
Developed Countries ◽  
Oxygen Depletion ◽  
Therapeutic Modalities ◽  
The Impact

The therapeutic repertoire for life-threatening inflammatory conditions like sepsis, graft-versus-host reactions, or colitis is very limited in current clinical practice and, together with chronic ones, like the osteoarthritis, presents growing economic burden in developed countries. This urges the development of more efficient therapeutic modalities like the mesenchymal stem cell-based approaches. Despite the encouraging in vivo data, however, clinical trials delivered ambiguous results. Since one of the typical features of inflamed tissues is decreased oxygenation, the success of cellular therapy in inflammatory pathologies seems to be affected by the impact of oxygen depletion on transplanted cells. Here, we examine our current knowledge on the effect of hypoxia on the physiology of bone marrow-derived mesenchymal stromal cells, one of the most popular tools of practical cellular therapy, in the context of their immune-modulatory capacity.

Examining the Impact of the Disabled Youth Peer Development Initiative: What are the Long-Term Outcomes?

2003 ◽  
Author(s):  
Teresa Garate-Serafini ◽  
Jose Mendez ◽  
Patty Arriaga ◽  
Larry Labiak ◽  
Carol Reynolds
Keyword(s):  
Long Term Outcomes ◽  
The Disabled ◽  
The Impact

scholarly journals Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease

2021 ◽  
Author(s):  
Rutao Wang ◽  
Scot Garg ◽  
Chao Gao ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Revascularization ◽  
Long Term Outcomes ◽  
Vital Status ◽  
Increased Risk ◽  
Artery Disease ◽  
The Impact

Abstract Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p < 0.001) compared to those without CVD. Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

scholarly journals Neuroimaging at Term Equivalent Age: Is There Value for the Preterm Infant? A Narrative Summary

Children ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 227
Author(s):  
Rudaina Banihani ◽  
Judy Seesahai ◽  
Elizabeth Asztalos ◽  
Paige Terrien Church
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Preterm Infant ◽  
Resonance Imaging ◽  
Long Term Outcomes ◽  
Equivalent Age ◽  
Current State ◽  
Patterns Of Injury ◽  
The Impact

Advances in neuroimaging of the preterm infant have enhanced the ability to detect brain injury. This added information has been a blessing and a curse. Neuroimaging, particularly with magnetic resonance imaging, has provided greater insight into the patterns of injury and specific vulnerabilities. It has also provided a better understanding of the microscopic and functional impacts of subtle and significant injuries. While the ability to detect injury is important and irresistible, the evidence for how these injuries link to specific long-term outcomes is less clear. In addition, the impact on parents can be profound. This narrative summary will review the history and current state of brain imaging, focusing on magnetic resonance imaging in the preterm population and the current state of the evidence for how these patterns relate to long-term outcomes.

scholarly journals Alloreactive Immune Response Associated to Human Mesenchymal Stromal Cells Treatment: A Systematic Review

2021 ◽  
Vol 10 (13) ◽  
pp. 2991
Author(s):  
Raquel Sanabria-de la Torre ◽  
María I. Quiñones-Vico ◽  
Ana Fernández-González ◽  
Manuel Sánchez-Díaz ◽  
Trinidad Montero-Vílchez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Immune Rejection ◽  
Human Mesenchymal Stromal Cells ◽  
Immunological Profile ◽  
Tolerability Data ◽  
Donor Specific Antibodies ◽  
The Impact ◽  
Hla Mismatches

The well-known immunomodulatory and regenerative properties of mesenchymal stromal cells (MSCs) are the reason why they are being used for the treatment of many diseases. Because they are considered hypoimmunogenic, MSCs treatments are performed without considering histocompatibility barriers and without anticipating possible immune rejections. However, recent preclinical studies describe the generation of alloantibodies and the immune rejection of MSCs. This has led to an increasing number of clinical trials evaluating the immunological profile of patients after treatment with MSCs. The objective of this systematic review was to evaluate the generation of donor specific antibodies (DSA) after allogeneic MSC (allo-MSC) therapy and the impact on safety or tolerability. Data from 555 patients were included in the systematic review, 356 were treated with allo-MSC and the rest were treated with placebo or control drugs. A mean of 11.51% of allo-MSC-treated patients developed DSA. Specifically, 14.95% of these patients developed DSA and 6.33% of them developed cPRA. Neither the production of DSA after treatment nor the presence of DSA at baseline (presensitization) were correlated with safety and/or tolerability of the treatment. The number of doses administrated and human leucocyte antigen (HLA) mismatches between donor and recipient did not affect the production of DSA. The safety of allo-MSC therapy has been proved in all the studies and the generation of alloantibodies might not have clinical relevance. However, there are very few studies in the area. More studies with adequate designs are needed to confirm these results.

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