scholarly journals Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease

2021 ◽  
Author(s):  
Yueyao Wang ◽  
Zhongwen Qi ◽  
Zhipeng Yan ◽  
Nan Ji ◽  
Xiaoya Yang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Cardiovascular Diseases ◽  
Immune Cell ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Cardiac Tissues ◽  
Inflammatory Microenvironment ◽  
Immune Cell Subsets ◽  
The Family

Abstract Mesenchymal stem cells (MSCs) belong to the family of pluripotent stem cells, which have an obvious multi-directional differentiation potential and can regulate the immune response of the organism by influencing immune cell subsets, thus they have excellent prospects for application in inflammation, immune diseases, and organ transplantation. Numerous studies have shown that MSCs are a promising strategy for the treatment of cardiovascular disease by modulating immune cell subsets and coordinating local and systemic innate and adaptive immune responses, thereby enabling the formation of a stable inflammatory microenvironment in damaged cardiac tissues. In this review, we summarize the mechanisms by which MSCs interact with immune cells and exert immunomodulatory effects, and explain the therapeutic effects of this mechanism in the treatment of cardiovascular diseases. A feasibility analysis is provided for the application of MSCs in cardiovascular diseases.

scholarly journals Mesenchymal Stem Cell Immunomodulation: A Novel Intervention Mechanism in Cardiovascular Disease

2022 ◽  
Vol 9 ◽  
Author(s):  
Yueyao Wang ◽  
Zhongwen Qi ◽  
Zhipeng Yan ◽  
Nan Ji ◽  
Xiaoya Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cardiovascular Diseases ◽  
Immune Cell ◽  
Differentiation Potential ◽  
Cardiac Tissues ◽  
Inflammatory Microenvironment ◽  
Lineage Differentiation ◽  
Immune Cell Subsets ◽  
Promising Source ◽  
Intervention Mechanism

Mesenchymal stem cells (MSCs) are the member of multipotency stem cells, which possess the capacity for self-renewal and multi-directional differentiation, and have several characteristics, including multi-lineage differentiation potential and immune regulation, which make them a promising source for cell therapy in inflammation, immune diseases, and organ transplantation. In recent years, MSCs have been described as a novel therapeutic strategy for the treatment of cardiovascular diseases because they are potent modulators of immune system with the ability to modulating immune cell subsets, coordinating local and systemic innate and adaptive immune responses, thereby enabling the formation of a stable inflammatory microenvironment in damaged cardiac tissues. In this review, the immunoregulatory characteristics and potential mechanisms of MSCs are sorted out, the effect of these MSCs on immune cells is emphasized, and finally the application of this mechanism in the treatment of cardiovascular diseases is described to provide help for clinical application.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

2019 ◽  
Vol 14 (4) ◽  
pp. 327-336 ◽  
Author(s):  
Carl R. Harrell ◽  
Marina Gazdic ◽  
Crissy Fellabaum ◽  
Nemanja Jovicic ◽  
Valentin Djonov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Amniotic Fluid ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Differentiation Potential ◽  
Differentiation Capacity ◽  
Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

scholarly journals Tailored Interventions to Improve Medication Adherence for Cardiovascular Diseases

2020 ◽  
Vol 11 ◽  
Author(s):  
Hai-Yan Xu ◽  
Yong-Ju Yu ◽  
Qian-Hui Zhang ◽  
Hou-Yuan Hu ◽  
Min Li
Keyword(s):  
Cardiovascular Disease ◽  
Medication Adherence ◽  
Cardiovascular Diseases ◽  
Healthcare Costs ◽  
Therapeutic Effects ◽  
Improve Medication Adherence ◽  
The Past ◽  
Tailored Interventions ◽  
Past Half Century ◽  
Past Half

Over the past half-century, medical research on cardiovascular disease (CVD) has achieved a great deal; however, medication adherence is unsatisfactory. Nearly 50% of patients do not follow prescriptions when taking medications, which limits the ability to maximize their therapeutic effects and results in adverse clinical outcomes and high healthcare costs. Furthermore, the effects of medication adherence interventions are disappointing, and tailored interventions have been proposed as an appropriate way to improve medication adherence. To rethink and reconstruct methods of improving medication adherence for CVD, the literature on tailored interventions for medication adherence focusing on CVD within the last 5 years is retrieved and reviewed. Focusing on identifying nonadherent patients, detecting barriers to medication adherence, delivering clinical interventions, and constructing theories, this article reviews the present state of tailored interventions for medication adherence in CVD and also rethinks the present difficulties and suggests avenues for future development.

scholarly journals Antioxidant Effects of Salidroside in the Cardiovascular System

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Siyu Sun ◽  
Qinhui Tuo ◽  
Dongxu Li ◽  
Xiulong Wang ◽  
Xuefang Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Health Risks ◽  
Therapeutic Strategies ◽  
Therapeutic Effects ◽  
Evidence Based ◽  
Human Health Risks ◽  
Bioactive Component ◽  
Antioxidant Effects

Cardiovascular disease is one of the main human health risks, and the incidence is increasing. Salidroside is an important bioactive component of Rhodiola rosea L., which is used to treat Alzheimer’s disease, tumor, depression, and other diseases. Recent studies have shown that salidroside has therapeutic effects, to some degree, in cardiovascular diseases via an antioxidative mechanism. However, evidence-based clinical data supporting the effectiveness of salidroside in the treatment of cardiovascular diseases are limited. In this review, we discuss the effects of salidroside on cardiovascular risk factors and cardiovascular diseases and highlight potential antioxidant therapeutic strategies.

Directions for Enhancement of the Therapeutic Efficacy of Mesenchymal Stem Cells in Different Neurodegenerative and Cardiovascular Diseases: Current Status and Future Perspectives

2021 ◽  
Vol 16 ◽  
Author(s):  
Lamiaa A. Ahmed ◽  
Khaled F. Al-Massri
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiovascular Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Current Status ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Apoptotic Effects

: Mesenchymal stem cells (MSCs) have shown promising therapeutic effects in a wide variety of medical conditions including neurodegenerative disorders and cardiovascular diseases. Although preliminary research has emphasized the ability of MSCs to engraft at sites of injury, several studies have revealed that MSCs mediate their effects through release of various paracrine factors, and through their antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. However, the clinical implications of MSCs application are limited due to their low survival rate in conditions of inflammation, oxidative stress, and nutrient restriction in damaged areas. Furthermore, the function of isolated MSCs is usually affected by the patient’s health. Therefore, it is necessary to develop new methods to enhance the therapeutic efficacy of MSCs under pathophysiological conditions. This review provides an overview of the general properties of MSCs, their therapeutic potential in neurodegenerative disorders such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease, as well as cardiovascular diseases such as myocardial infarction, diabetic cardiomyopathy, and dilated cardiomyopathy, and their related mechanisms. In addition, this review also discusses potential problems and side effects, as well as current and future directions for improvement of MSCs therapy and their implications and applications.

MO695THE ASSOCIATION OF CIRCULATING CD14++CD16+ MONOCYTES, NATURAL KILLER CELLS AND REGULATORY T CELLS SUBPOPULATIONS WITH CARDIOVASCULAR DISEASE IN A COHORT OF PERITONEAL DIALYSIS PATIENTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Anila Duni ◽  
Olga Balafa ◽  
George Vartholomatos ◽  
Margarita Oikonomou ◽  
Paraskevi Tseke ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
T Cells ◽  
Peritoneal Dialysis ◽  
Nk Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Normal Range ◽  
Immune Cell Subsets ◽  
Cell Subpopulations

Abstract Background and Aims Advanced chronic kidney disease (CKD) is characterized by elevated expression of the proinflammatory and pro-atherogenic CD14++CD16+ monocytes subset. The role of lymphocyte subpopulations including natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention. The role of immune cell subpopulations remains to be determined in peritoneal dialysis (PD) patients. The aim of this pilot study was to investigate potential correlations between blood levels of CD14++CD16+ monocytes, NK cells and Tregs with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in a cohort of PD patients. Method 29 stable PD patients (mean age 66.96 years ±14.5, 62% males) were enrolled. Exclusion criteria were a history of malignancy, autoimmune disease, active or chronic infections and a recent (< 3 months) cardiovascular event. Demographic, laboratory and bioimpedance measurements data (overhydration, extracellular and total body water and their ratios) were collected. The analysis of peripheral blood immune cell subsets was performed using flow cytometry (FC). Additionally, in 7 PD patients the distribution of the immune cells was evaluated by FC at two time points: T0 (before initiation of PD - CKD stage G5) and T1 (after PD start). Results The median dialysis vintage was 34.5 (range 3.2-141) months. Overall, PD patients had 527 ± 199 monocytes and 1731 ± 489 lymphocytes while mean percentage of CD14++CD16+ monocytes was 9.3 ±6.36% (normal range 2-8%), NK cells 16.6±10.3% (normal range 5-15%) and Tregs 2.1±1.76% (normal range 1-3%). There was no correlation of either of these cell subpopulations with age, PD vintage, inflammation markers (CRP, fibrinogen, albumin, hsTroponin-I), overhydration markers or comorbidities. Only increased NK cells were associated with the presence of HF in PD (24.87 vs 14.92%, p 0.047). In multiple regression analysis, NK cells levels were strongly associated with the presence of edema (beta coef=13.7, p<0.001) and CAD (beta coef=7.1, p=0.046). At T0 mean percentage of CD14++CD16+ monocytes, NK cells and Tregs were 9.7 ±4.5%, 17.1 ±3.84% and 2.38± 1.26% respectively whereas at T1 mean percentage of CD14++CD16+ monocytes was 13.3% ±8.4, NK cells 19.8±6.47% and Tregs 1.5±0.6%. Paired t-test of cell subpopulations (T0 vs T1) showed that only the Tregs were significantly decreased (p =0.018), while the other subpopulations did not differ and remained increased. Conclusion Our study is the first to evaluate the potential association between specific immune cell subsets and cardiovascular disease in long-term PD patients. Increased NK cells levels directly correlate both with the presence of HF and CAD in PD patients. Longitudinal results suggest that CD14++CD16+ and NK cells remain increased after PD start, while Tregs decrease further. The state of pro-inflammation and immune deregulation appear to persist after initiating PD. Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients who are at the highest risk for complications and to guide interventions that may improve clinical outcomes.

Abstract 138: The Use of β-1.3/1.6-D-Glucan as Complementary Therapy for Cardiovascular Diseases

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Peter Sugita
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Cardiovascular Diseases ◽  
Ganoderma Lucidum ◽  
Bypass Surgery ◽  
Heart Function ◽  
Complementary Therapy ◽  
Beta Glucan ◽  
Standard Drug ◽  
Surgery Patient

Cardiovascular disease nowadays is still the one silent killer over the world.So far, current standard therapies for cardiovascular diseases do not reach expected results such as the improving heart function by rehabilitating the damaged cardiomyocytes For thousands of years Ganoderma lucidum extract has been used as herbal therapy for various types of diseases, including cardiovascular diseases. An International Publication No. WO 2005/084692 A2 with the title Effect of Glucan on Stem Cell Recruitment and Tissue Repair mentions that “ the orally administered glucan enhances proliferation, activation and differentiation of committed stem progenitor cells by functioning with the complement system by providing a second signal for CR3 activation .” Furthermore, it is also discussed that “ the committed stem cells are selected from the group consisting of committed stem cells from the liver, heart, muscle, kidney and neural tissue .” In 1995 we began a research on β-D-Glucan derived from the purified extract of East-Java Indonesian Ganoderma lucidum mycelia.At the end of 2009 we have the first clinical experience the use of our β-1.3/1.6-D-Glucan for cardiovascular diseases patient. A bypass surgery patient who was also a candidate for heart transplant experienced a good clinical result after 8 months use of our beta glucan with dose of 3 x 200 mg beta glucan a day. A significant improvement of Ejection Fraction (EF) was reached from 22% to 44%. Previously, when he only took standard drug therapy for cardiovascular disease after bypass surgery, the improvement of EF was not significant (from 13% as baseline to 22%).This result also applied to 4 other patients. We presumed that this specific Ganoderma lucidum β-D-Glucan has similar mechanism of actions as mentioned in the above publication and also in a journal Modulating Toll-like receptor mediated signaling by(1-3)-β-D-glucan rapidly induces cardioprotection . The conclusion is β-D-Glucan could serve as a complementary therapy in cardiovascular diseases but it still needs further investigations through in vitro / in vivo assays and clinical trials.

scholarly journals Additive Therapeutic Effects of Mesenchymal Stem Cells and IL-37 for Systemic Lupus Erythematosus

2019 ◽  
Vol 31 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Jianyong Xu ◽  
Jieting Chen ◽  
Wenlei Li ◽  
Wei Lian ◽  
Jieyong Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lupus Erythematosus ◽  
Spleen Weight ◽  
Therapeutic Effects ◽  
Mice Model ◽  
Autoantibody Production ◽  
Inflammatory Microenvironment ◽  
Proinflammatory Factors

BackgroundAlthough mesenchymal stem cells (MSCs) might offer a promising strategy for treating SLE, their immunoregulatory plasticity makes their therapeutic effects unpredictable. Whether overexpressing IL-37, an IL-1 family member with immunosuppressive activity, might enhance the therapeutic effects of these cells for SLE is unknown.MethodsWe genetically modified MSCs to overexpress IL-37 and assessed their effects on immune suppression in vitro. We also evaluated the effects of such cells versus effects of various controls after transplanting them into MRL/lpr mice (model of SLE).ResultsStem cell characteristics did not appear altered in MSCs overexpressing IL-37. These cells had enhanced immunosuppression in vitro in terms of inhibiting splenocyte proliferation, reducing proinflammatory factors (IL-1β, TNF-α, IL-17, and IL-6), and suppressing autoantibodies (anti-dsDNA and anti-ANA). Compared with animals receiving control MSCs or IL-37 treatment alone, MRL/lpr mice transplanted with IL-37–overexpressing cells displayed improved survival and reduced signs of SLE (indicated by urine protein levels, spleen weight, and renal pathologic scores); they also had significantly lower expression of proinflammatory factors, lower total antibody levels in serum and urine, lower autoantibody production, and showed reduced T cell numbers in the serum and kidney. Expression of IL-37 by MSCs can maintain higher serum levels of IL-37, and MSCs had prolonged survival after transplantation, perhaps through IL-37 suppressing the inflammatory microenvironment.ConclusionsMutually reinforcing interaction between MSCs and IL-37 appears to underlie their additive therapeutic effects. Genetic modification to overexpress IL-37 might offer a way to enhance the stability and effectiveness of MSCs in treating SLE.

CD10/Neprilysin Enrichment in Infrapatellar Fat Pad–Derived Mesenchymal Stem Cells Under Regulatory-Compliant Conditions: Implications for Efficient Synovitis and Fat Pad Fibrosis Reversal

2020 ◽  
Vol 48 (8) ◽  
pp. 2013-2027 ◽  
Author(s):  
Dimitrios Kouroupis ◽  
Annie C. Bowles ◽  
Thomas M. Best ◽  
Lee D. Kaplan ◽  
Diego Correa
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Infrapatellar Fat Pad ◽  
Therapeutic Effects ◽  
Fat Pad ◽  
In Vitro Proliferation ◽  
Differentiation Potential

Background: Synovitis and infrapatellar fat pad (IFP) fibrosis participate in various conditions of the knee. Substance P (SP), a neurotransmitter secreted within those structures and historically associated with nociception, also modulates local neurogenic inflammatory and fibrotic responses. Exposure of IFP mesenchymal stem cells (IFP-MSCs) to a proinflammatory/profibrotic environment (ex vivo priming with TNFα, IFNγ, and CTGF) induces their expression of CD10/neprilysin, effectively degrading SP in vitro and in vivo. Purpose/Hypothesis: The purpose was to test the therapeutic effects of IFP-MSCs processed under regulatory-compliant protocols, comparing them side-by-side with standard fetal bovine serum (FBS)–grown cells. The hypothesis was that when processed under such protocols, IFP-MSCs do not require ex vivo priming to acquire a CD10-rich phenotype efficiently degrading SP and reversing synovitis and IFP fibrosis. Study Design: Controlled laboratory study. Methods: Human IFP-MSCs were processed in FBS or either of 2 alternative conditions—regulatory-compliant pooled human platelet lysate (hPL) and chemically reinforced medium (Ch-R)—and then subjected to proinflammatory/profibrotic priming with TNFα, IFNγ, and CTGF. Cells were assessed for in vitro proliferation, stemness, immunophenotype, differentiation potential, transcriptional and secretory profiles, and SP degradation. Based on a rat model of acute synovitis and IFP fibrosis, the in vivo efficacy of cells degrading SP plus reversing structural signs of inflammation and fibrosis was assessed. Results: When compared with FBS, IFP-MSCs processed with either hPL or Ch-R exhibited a CD10High phenotype and showed enhanced proliferation, differentiation, and immunomodulatory transcriptional and secretory profiles (amplified by priming). Both methods recapitulated and augmented the secretion of growth factors seen with FBS plus priming, with some differences between them. Functionally, in vitro SP degradation was more efficient in hPL and Ch-R, confirmed upon intra-articular injection in vivo where CD10-rich IFP-MSCs also dramatically reversed signs of synovitis and IFP fibrosis even without priming or at significantly lower cell doses. Conclusion: hPL and Ch-R formulations can effectively replace FBS plus priming to induce specific therapeutic attributes in IFP-MSCs. The resulting fine-tuned, regulatory-compliant, cell-based product has potential future utilization as a novel minimally invasive cell therapy for the treatment of synovitis and IFP fibrosis. Clinical Relevance: The therapeutic enhancement of IFP-MSCs manufactured under regulatory-compliant conditions suggests that such a strategy could accelerate the time from preclinical to clinical phases. The therapeutic efficacy obtained at lower MSC numbers than currently needed and the avoidance of cell priming for efficient results could have a significant effect on the design of clinical protocols to potentially treat conditions involving synovitis and IFP fibrosis.

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