Abstract 360: IL-10-inhibits Pressure Overload-induced Homing, Proliferation And Differentiation Of Non-resident Fibroblast Progenitors And Improve Heart Function.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Suresh K Verma ◽  
Prasanna Krishnamurthy ◽  
David Barefield ◽  
Alexander R Mackie ◽  
Erin E Vaughan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Cardiac Fibrosis ◽  
Heart Function ◽  
Pressure Overload ◽  
Aortic Constriction ◽  
Genes Expression ◽  
Proliferation And Differentiation ◽  
Fibroblast Progenitor Cells

Background: Recently we have shown that IL-10, an anti-inflammatory cytokine, markedly inhibited the pressure overload-induced cardiac fibrosis, however, antifibrotic mechanisms of IL-10 are largely unknown. In most of organs, including heart, extracellular matrix (ECM) remodeling is primarily mediated by excessive proliferation of activated fibroblasts and myofibroblasts. Here we hypothesized that IL-10 inhibits stress-induced homing, proliferation and differentiation of nonresident bone marrow-derived fibroblast progenitor cells and therefore, attenuates cardiac remodeling and improves of heart function. Methods and Results: Cardiac hypertrophy was induced in Wild-type (WT) and IL-10-knockout (KO) mice by transverse aortic constriction (TAC). TAC-induced left ventricular (LV) dysfunction and fibrosis were further exaggerated in KO mice compared to WT. TAC significantly increased TGF-β, collagen Iα and IIIα genes expression. Systemic recombinant mouse IL-10 administration markedly improved LV function, inhibited TAC-induced cardiac fibrosis and fibrosis associated genes expression. To identify the role of fibroblast progenitor cells (FPCs), we measured the mobilization of FPCs (Prominin1 positive cells) from bone marrow to heart by FACs. Exacerbated mobilization of FPCs in peripheral blood and heart in IL-10 KO mice were found 3 and 7 days after aortic constriction. Bone marrow transplantation experiments were performed where WT-GFP positive marrow was transplanted in BM depleted IL-10 KO mice. TAC-induced mobilization was significantly reduced in WT-transplanted marrow as compare to TAC-IL-10 KO mice. To identify the role IL-10 on TGFβ-induced endothelial cells trans-differentiation to myofibroblasts, we treated aortic endothelial cells with IL-10 and TGFβ2 for 96 hrs. Both Immunocytochemistry and Western blot analysis results suggested that TGF-β2-induced EndMT was significantly inhibited by IL-10 treatment. To understand the mechanisms, we found that TGF-β2-induced Notch1 signaling was reduced by IL-10. Conclusion: Taken together our observations suggest that the anti-fibrotic effects of IL-10 treatment are mediated by reduced proliferation and differentiation of non-resident myofibroblasts.

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

scholarly journals The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Naosuke Kamei ◽  
Kivanc Atesok ◽  
Mitsuo Ochi
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Endothelial Cells ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Tissue Repair ◽  
Cell Populations ◽  
Neural Tissues ◽  
Cell Source ◽  
Stem Cell Populations

Endothelial progenitor cells (EPCs) derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+) cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

scholarly journals Circulating stem and progenitor cells as markers of inflammation, endothelial regeneration, and prediction of vascular complications in metabolic syndrome and type 1 and 2 diabetes mellitus

2018 ◽  
pp. 58-67
Author(s):  
О.В. Першина ◽  
А.В. Пахомова ◽  
Н.Н. Ермакова ◽  
О.Ю. Рыбалкина ◽  
В.А. Крупин ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Progenitor Cells ◽  
Vascular Complications ◽  
Endothelial Regeneration

Цель исследования состояла в выявлении информативных клеточных маркеров сосудистых осложнений, регенерации микрососудистой сети и воспаления в венозной крови здоровых волонтеров, больных с метаболическим синдромом, сахарным диабетом 1 и 2 типа. Методы. Обследованы больные с метаболическим синдромом (МС), диабетом 2 типа без осложнений, диабетом 1 типа средней степени тяжести и здоровые волонтеры. Диагноз пациентов подтвержден общеклиническими, биохимическими, коагулометрическими и иммуноферментными методами исследования, для оценки экспрессии антигенов использовался многопараметрический цитометрический анализ. Результаты. При анализе экспрессии маркеров показано изменение числа эндотелиальных клеток, мезенхимальных стволовых клеток (МСК) и гемопоэтических стволовых клеток (ГСК) в крови в зависимости от патологии. Эндотелиальные клетки миелоидного (CD45CD14CD34CD309CD144CD31) и немиелоидного (CD45CD14CD34CD309CD144CD31) происхождения, CD309-эндотелиальные клетки и МСК (CD44CD73CD90CD105) предлагаются в качестве маркеров повреждения эндотелия при диабетической симптоматике. При этом ГСК (CD45CD34) могут выступать ценным диагностическим и прогностическим маркером воспаления. Заключение. Для подтверждения сосудистых повреждений и прогноза развития осложнений при диабете 1 и 2 типа в венозной крови пациентов целесообразно оценивать эндотелиальные прогениторные клетки (ЭПК) не костномозговой локализации (CD31CD309CD144) и костномозговой локализации (CD34CD309), и ЭПК c высоким регенеративным потенциалом (CD45CD34CD31CD144). Циркулирующие ЭПК, формирующие колонии in vitro (CD45CD34CD31), рекомендуется использовать в качестве дифференциального маркера состояния регенерации эндотелия при диабете 2 типа. The aim of this study was to identify mesenchymal stem cells (MSC), hematopoietic stem cells (HSC), mature endothelial cells, and endothelial progenitor cells (EPC) in the blood of healthy volunteers, patients with metabolic syndrome, and type 1 and 2 diabetes mellitus as new, informative cellular markers of vascular complications, endothelial regeneration, and inflammation. Methods. The diagnosis was confirmed by general clinical, biochemical, coagulometeric and ELISA studies; multi-parameter cytometric assay was used for evaluation of antigen expression. Results. Changes in the count of MSC, HSC, mature endothelial cells, and endothelial progenitor cells in blood of patients with metabolic syndrome and type 1 and 2 diabetes depended on the type of pathology. We propose using endothelial cells of myeloid (CD45CD14CD34CD309CD144CD31) and non-myeloid origin (CD45CD14CD34CD309CD144CD31), CD309-endothelial cells, and MSCs with the CD44CD73CD90CD105 phenotype as nonspecific markers of endothelial damage in presence of diabetic symptoms. Furthermore, HSCs (CD45CD34) can be used as a valuable diagnostic and prognostic marker of inflammation. Conclusions. It is relevant to evaluate EPCs of non-bone marrow localization (CD31CD309CD144) and bone marrow localization (CD34CD309) and EPCs with a high regenerative potential (CD45CD34CD31CD144) in the blood of patients with type 1 and 2 diabetes to confirm the presence of vascular damage and predict development of complications. Circulating, in vitro colony-forming EPCs (CD45CD34CD31) are recommended as a differential marker for inhibition of endothelial regeneration in type 2 diabetes.

Abstract 353: Bone Marrow Fibroblast Progenitor Cell-derived Exosomes Activate Resident Fibroblast and Augment Pressure Overload Induced Cardiac Fibrosis in IL10KO Mice

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Suresh K Verma ◽  
Venkata N Girikipathi ◽  
Maria Cimini ◽  
Zhongjian Cheng ◽  
Moshin Khan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cardiac Fibrosis ◽  
Culture Media ◽  
Critical Role ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiac Fibroblast ◽  
Paracrine Factors ◽  
Fibroblast Activation ◽  
Resident Fibroblast

Background: Activated fibroblasts (myoFBs) play critical role in cardiac fibrosis, however, their origin in diseased heart remains uncertain. Previous studies suggest the contribution of bone marrow fibroblasts progenitor cells (FPC) in pressure overload (PO)-induced cardiac fibrosis and inflammation acts as catalyst in this process. Recently others and we have shown that paracrine mediators packaged in exosomes play important role in cardiac pathophysiology. Thus, we hypothesized that exosome-derived from IL10KO-FPC augments PO-induced resident cardiac fibroblast activation and therefore, aggravate cardiac fibrosis. Methods and Results: Cardiac fibrosis was induced in Wild-type (WT) and IL10-knockout (IL10KO) mice by transverse aortic constriction (TAC). TAC-induced left ventricular (LV) dysfunction and fibrosis were further exaggerated in IL10KO mice. PO-enhanced FPC (Prominin1 + cells) mobilization and homing in IL10KO mice compared to WT mice. To establish the IL10KO-FPC paracrine signaling, exosomes were isolated from WT and IL10KO BM-FPC culture media and characterized for proteins/miRNA. IL10 KO FPC-exosomes showed altered packaging of signature fibrotic miR and proteins. To explore whether FPC-exosomes modulate resident fibroblast activation, adult cardiac fibroblasts were treated with WT and IL10KO FPC-derived exosomes. IL10KO-FPC-derived exosomes exaggerate TGFβ 2 -induced activation of adult fibroblasts. These data suggest that fibrotic remodeling factors (miRs and/or proteins) packaged in IL10KO-FPC exosomes are sufficient to enhance the resident cardiac fibroblast activation and mediate cardiac fibrotic remodeling IL10 treatment significantly inhibits TGFβ 2 -induced FPC to myoFBs transition. Conclusion: Taken together, our findings suggest that paracrine factors secreted by BM-FPC augment resident cardiac fibroblast activation and fibrosis in pressure overloaded myocardium and IL10 negatively regulates this process. Ongoing investigations using molecular approaches will provide a better understanding on the mechanistic and therapeutic aspects of IL10 on PO-induced cardiac fibrosis and heart failure.

scholarly journals Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 10-19 ◽  
Author(s):  
S Rafii ◽  
F Shapiro ◽  
J Rimarachin ◽  
RL Nachman ◽  
B Ferris ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Cell Adhesion ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Divalent Cations ◽  
Hematopoietic Cells ◽  
Hematopoietic Progenitor Cell ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Abstract To examine potential mechanisms by which hematopoiesis may be regulated by endothelial cells within the bone marrow (BM) microenvironment, we have devised a technique for the in vitro study of the interaction of human BM microvascular endothelial cells (BMEC) with hematopoietic cells. Microvessels isolated by collagenase digestion of spicules obtained from filtered BM aspirate were plated on gelatin-coated plastic dishes, and colonies of endothelial cells grown from microvessel explants were further purified by Ulex europaeus lectin affinity separation. BMEC monolayers isolated by this technique grew in typical cobblestone fashion, stained positively with antibody to factor VIII/von Willebrand factor, and incorporated acetylated LDL. Immunohistochemical studies showed that BM microvessels and BMEC monolayers express CD34, PECAM, and thrombospondin. Incubation of resting BMEC with BM mononuclear hematopoietic cells resulted in the selective adhesion of relatively large numbers of CD34+ progenitor cells and megakaryocytes. The binding of purified BM-derived CD34+ progenitor cells to BMEC was dependent on divalent cations and was partially blocked by antibodies to CD34. IL-1 beta treatment of BMEC monolayers resulted in an increase of CD34+ progenitor cell adhesion by mechanisms independent of CD34 or divalent cations. BMEC exhibit specific affinity for CD34+ progenitor cells and megakaryocytes, suggesting that the BM microvasculature may play a role in regulating the trafficking, proliferation, and differentiation of lineage specific hematopoietic elements, and possibly of pluripotent stem cells within the CD34+ population.

scholarly journals Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Jianyong Qi ◽  
Qin Liu ◽  
Kaizheng Gong ◽  
Juan Yu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Study Groups ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Cardioprotective Effects

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy.Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot.Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P<0.05).Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

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