scholarly journals Cardiac progenitor cell sheets secrete proangiogenic growth factors and locally activate capillarogenesis after infarction

2021 ◽  
Vol 10 (3) ◽  
pp. 34-43
Author(s):  
K. V. Dergilev ◽  
Z. I. Tsokolaeva ◽  
Yu. D. Vasilets ◽  
I. B. Beloglazova ◽  
E. V. Parfenova
Keyword(s):  
Myocardial Infarction ◽  
Growth Factors ◽  
Heart Diseases ◽  
Cell Sheet ◽  
Antibody Array ◽  
Matrix Remodeling ◽  
Post Transplantation ◽  
Cell Sheets ◽  
Hypoxic Conditions

Background.      The application of tissue-engineered constructs that simulate the natural microenvironment of cells, maintain their viability and functional properties, is a new promising route for the treatment of ischemic diseases. However, the mechanisms that ensure the effectiveness of this type of treatment and the principles of choosing the optimal population of progenitor cells remain poorly understood.        Aim. To study the profile of secretion of proangiogenic growth factors of cardiosphere-derived cell sheet (CS), and to study the effect of their transplantation on postinfarction myocardial vascularization.            Methods. Assembly of cardiosphere-derived cell sheets were performed on thermosensitive culture plates. Characterization of cell sheets was performed using immunofluorescence staining and a commercial kit for the determination of proangiogenic factors “Mouse Angiogenesis Antibody Array”. The evaluation of the angiogenic properties of the cell graft in vivo was carried out using a rat myocardial infarction model.              Results. It was found that the cardiosphere-derived cell sheet secrete factors involved in the regulation of vasculo-/angiogenesis. At the same time, the cultivation of cell sheets under hypoxic conditions (3% O2) led to an increase in the secretion of proangigenic factors VEGF and pIgF, fGf-1, FGF-2, endothelin-1, as well as MMP-9, which is involved in extracellular matrix remodeling. Cell sheet transplantation on the epicardial surface of the heart after myocardial infarction ensures cell viability and local increase in capillarization of the damaged area. Conclusion. Thus, the application of cardiosphere-derived cell sheets, which have proangiogenic properties and ability to maintain post transplantation cell survival, can be considered as a promising approach for the development of new methods of therapy for heart diseases

scholarly journals Stem cell-derived cell sheet transplantation for heart tissue repair in myocardial infarction

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rui Guo ◽  
Masatoshi Morimatsu ◽  
Tian Feng ◽  
Feng Lan ◽  
Dehua Chang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cell ◽  
Tissue Repair ◽  
Cardiac Tissue ◽  
Cell Sheet ◽  
Clinical Manifestations ◽  
Induced Pluripotent Stem Cell ◽  
Heart Tissue ◽  
Therapeutic Effects ◽  
Cell Sheets

AbstractStem cell-derived sheet engineering has been developed as the next-generation treatment for myocardial infarction (MI) and offers attractive advantages in comparison with direct stem cell transplantation and scaffold tissue engineering. Furthermore, induced pluripotent stem cell-derived cell sheets have been indicated to possess higher potential for MI therapy than other stem cell-derived sheets because of their capacity to form vascularized networks for fabricating thickened human cardiac tissue and their long-term therapeutic effects after transplantation in MI. To date, stem cell sheet transplantation has exhibited a dramatic role in attenuating cardiac dysfunction and improving clinical manifestations of heart failure in MI. In this review, we retrospectively summarized the current applications and strategy of stem cell-derived cell sheet technology for heart tissue repair in MI.

scholarly journals Fabrication of hyaline-like cartilage constructs using mesenchymal stem cell sheets

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hallie Thorp ◽  
Kyungsook Kim ◽  
Makoto Kondo ◽  
David W. Grainger ◽  
Teruo Okano
Keyword(s):  
Chondrogenic Differentiation ◽  
Cell Sheet ◽  
Cartilage Regeneration ◽  
Cell Sheets ◽  
Chondrogenic Potential ◽  
Cell Sheet Technology ◽  
Cell Functionality ◽  
Articular Cartilage Regeneration

AbstractCell and tissue engineering approaches for articular cartilage regeneration increasingly focus on mesenchymal stem cells (MSCs) as allogeneic cell sources, based on availability and innate chondrogenic potential. Many MSCs exhibit chondrogenic potential as three-dimensional (3D) cultures (i.e. pellets and seeded biomaterial scaffolds) in vitro; however, these constructs present engraftment, biocompatibility, and cell functionality limitations in vivo. Cell sheet technology maintains cell functionality as scaffold-free constructs while enabling direct cell transplantation from in vitro culture to targeted sites in vivo. The present study aims to develop transplantable hyaline-like cartilage constructs by stimulating MSC chondrogenic differentiation as cell sheets. To achieve this goal, 3D MSC sheets are prepared, exploiting spontaneous post-detachment cell sheet contraction, and chondrogenically induced. Results support 3D MSC sheets’ chondrogenic differentiation to hyaline cartilage in vitro via post-contraction cytoskeletal reorganization and structural transformations. These 3D cell sheets’ initial thickness and cellular densities may also modulate MSC-derived chondrocyte hypertrophy in vitro. Furthermore, chondrogenically differentiated cell sheets adhere directly to cartilage surfaces via retention of adhesion molecules while maintaining the cell sheets’ characteristics. Together, these data support the utility of cell sheet technology for fabricating scaffold-free, hyaline-like cartilage constructs from MSCs for future transplantable articular cartilage regeneration therapies.

scholarly journals Grape Seed Proanthocyanidin Extract Ameliorates Cardiac Remodelling After Myocardial Infarction Through PI3K/AKT Pathway in Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Yongxue Ruan ◽  
Qike Jin ◽  
Jingjing Zeng ◽  
Fangfang Ren ◽  
Zuoyi Xie ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Dysfunction ◽  
Grape Seed ◽  
Akt Pathway ◽  
Grape Seeds ◽  
Hypoxic Conditions ◽  
Grape Seed Proanthocyanidin Extract ◽  
Grape Seed Proanthocyanidin

Myocardial infarction is one of the most serious fatal diseases in the world, which is due to acute occlusion of coronary arteries. Grape seed proanthocyanidin extract (GSPE) is an active compound extracted from grape seeds that has anti-oxidative, anti-inflammatory and anti-tumor pharmacological effects. Natural products are cheap, easy to obtain, widely used and effective. It has been used to treat numerous diseases, such as cancer, brain injury and diabetes complications. However, there are limited studies on its role and associated mechanisms in myocardial infarction in mice. This study showed that GSPE treatment in mice significantly reduced cardiac dysfunction and improved the pathological changes due to MI injury. In vitro, GSPE inhibited the apoptosis of H9C2 cells after hypoxia culture, resulting in the expression of Bax decreased and the expression of Bcl-2 increased. The high expression of p-PI3K and p-AKT was detected in MI model in vivo and in vitro. The use of the specific PI3K/AKT pathway inhibitor LY294002 regressed the cardio-protection of GSPE. Our results showed that GSPE could improve the cardiac dysfunction and remodeling induced by MI and inhibit cardiomyocytes apoptosis in hypoxic conditions through the PI3K/AKT signaling pathway.

scholarly journals Transplantation of Cardiac Mesenchymal Progenitor Cell Sheets for Myocardial Vascularization after an Infarction (Experimental Study)

2018 ◽  
Vol 14 (6) ◽  
pp. 28-40 ◽  
Author(s):  
Konstantin V. Dergilev ◽  
Zoya I. Tsokolaeva ◽  
Ivan A. Ryzhkov ◽  
Elena V. Parfenova
Keyword(s):  
Myocardial Infarction ◽  
Growth Factors ◽  
Progenitor Cells ◽  
Connexin 43 ◽  
Solid Phase ◽  
Reference Group ◽  
Right Atrial ◽  
Rational Approach ◽  
Mesenchymal Progenitor Cells ◽  
Cell Sheets

Purpose. To develop a method of producing tissue-engineered constructs (TECs) on the basis of resident mesenchymal progenitor cells (MPC) of the human heart and to assess the effect of TECs transplantation on regenerative processes in the heart using a model of myocardial infarction in rats.Materials and methods. Human resident MPCs were isolated from the right atrial auricle of CAD patients. A similar protocol was used to obtain MPCs from Wistar rats. The MPC immunophenotype was determined by cytofluorometry. Corresponding TECs were obtained on the basis of MPC sheets of human and rats' hearts. Myocardial infarction in rats was induced by ligation of the anterior descending coronary artery followed by TEC transplantation. Euthanasia was performed 30 days after the transplantation. Histological examination of the implant and vascularization cells, morphometric analysis, tracking of the MPC differentiation ability, determination of the content of growth factors by solid-phase ELISA were carried out. Statistical evaluation of the significance of differences was performed using the Statistica 8.0 software package.Results. The analysis of the obtained cell constructs showed that they consisted of several layers of cells interacting with each other by means of connexin 43 and were characterized by good cell viability as a part TECs. The number of vessels in the peri-infarction area under the transplant from the MPC was significantly higher than that in the reference group with signs of differentiation of cardiac MPCs transplanted into endothelial vascular cells.The increased vascularization was combined with an increase in the area of viable myocardial sites and a decrease in LV cavity dilation. Analysis of the cardiac MPC secretion products showed that they produce the most important growth factors and cytokines that regulate angiogenesis and migration of stem cells.Conclusion. The strategy of using epicardial TEC transplantation based on MPC sheets seems to be a rational approach for effective delivery of viable stem/progenitor cells to the damaged myocardium. The use of TEC helps to reduce or temporarily eliminate the effect of factors that contribute to progressive heart dysfunction by local paracrine exposure and activation of the revascularization processes in the affected zone.

scholarly journals Scaffold-Free 3-D Cell Sheet Technique Bridges the Gap between 2-D Cell Culture and Animal Models

2019 ◽  
Vol 20 (19) ◽  
pp. 4926 ◽  
Author(s):  
Ayidah Alghuwainem ◽  
Alaa T. Alshareeda ◽  
Batla Alsowayan
Keyword(s):  
Tissue Engineering ◽  
Cell Culture ◽  
Animal Models ◽  
Tissue Repair ◽  
Cell Sheet ◽  
Cell Sheets ◽  
Systemic Injection ◽  
In Vivo Testing ◽  
D Cell

Various tissue engineering techniques have been created in research spanning two centuries, resulting in new opportunities for growing cells in culture and the creation of 3-D tissue-like constructs. These techniques are classified as scaffold-based and scaffold-free techniques. Cell sheet, as a scaffold-free technique, has attracted research interest in the context of drug discovery and tissue repair, because it provides more predictive data for in vivo testing. It is one of the most promising techniques and has the potential to treat degenerative tissues such as heart, kidneys, and liver. In this paper, we argue the advantages of cell sheets as a scaffold-free approach, compared to other techniques, including scaffold-based and scaffold-free techniques such as the classic systemic injection of cell suspension.

АДАПТАЦИЯ МЕТОДА ИНТЕРФЕРОМЕТРИИ СЛОЯ БИОМОЛЕКУЛ ДЛЯ КОЛИЧЕСТВЕННОЙ ОЦЕНКИ СОДЕРЖАНИЯ ФАКТОРА РОСТА ЭНДОТЕЛИЯ СОСУДОВ В КОНДИЦИОНИРОВАННОЙ КЛЕТОЧНОЙ СРЕДЕ

2020 ◽  
Vol 65 (6) ◽  
pp. 1099-1106
Author(s):  
М.В. Волкова ◽  
◽  
В.В. Бояринцев ◽  
А.В. Трофименко ◽  
С.А. Бирюков ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
High Sensitivity ◽  
Conditioned Media ◽  
Enzyme Linked Immunosorbent Assay ◽  
Growth Media ◽  
Cell Sheets ◽  
Hypoxic Conditions ◽  
Endothelial Growth Factor

Quantitative analysis of cytokines, chemokines, growth factors and other soluble proteins in different biological liquids is routinely performed in contemporary diagnostics and biomedicine research. However, current methods of analysis are time-consuming and include multiple steps. In this study, we have developed a protocol that describes how bio-layer interferometry can be applied to quantify an analyte in several minutes. Conditioned growth media collected from mouse mesenchymal stem cells grown in normoxia or hypoxic conditions in a monolayer fashion, MSC-derived 3D cell sheets and 3D spheroids were used as a model system in which we determined a concentration of vascular endothelial growth factor (VEGF-A). This technique displayed a high sensitivity (down to 0.1 ng of VEGF-A per mL as a minimum). The measured concentrations of VEGF-A in the conditioned media from mesenchymal stem cells turned out to be similar with values determined by the enzyme-linked immunosorbent assay. Using bio-layer interferometry, it was shown that as compared to mesenchymal stem cells grown in monolayer, spheroids and 3D sheets of mesenchymal stem cells produce significantly more VEGF-A (by 2.5-3.0-fold). Thus, due to the developed protocol it was possible to adapt bio-layer interferometry for rapid quantification of growth factors in conditioned media.

scholarly journals Proangiogenic role of neutrophil-like inflammatory heterophils during neovascularization induced by growth factors and human tumor cells

Blood ◽  
2006 ◽  
Vol 107 (1) ◽  
pp. 317-327 ◽  
Author(s):  
Andries Zijlstra ◽  
Marco Seandel ◽  
Tatyana A. Kupriyanova ◽  
Juneth J. Partridge ◽  
Mark A. Madsen ◽  
...  
Keyword(s):  
Growth Factors ◽  
Blood Vessel ◽  
Tumor Cells ◽  
Chorioallantoic Membrane ◽  
Human Tumor ◽  
Inflammatory Cells ◽  
Specific Marker ◽  
Matrix Remodeling ◽  
Functional Involvement

Abstract A quantitative in vivo angiogenesis model employing collagen onplants placed on the chick embryo chorioallantoic membrane (CAM) has been used in this study to assess the spatial and temporal associations between neutrophil-like inflammatory cells, namely chicken heterophils, and the development of new blood vessels. Previously we have demonstrated that monocytes/macrophages infiltrating the onplants were associated with extracellular matrix remodeling and angiogenesis, in particular by delivering MMP-13 collagenase. By introducing chicken gelatinase B (chMMP-9) as a specific marker for heterophils, we now show that the onset and extent of angiogenesis induced by purified growth factors or by human HT-1080 fibrosarcoma cells correlated with the initial influx of chMMP-9–positive heterophils. This early heterophil arrival was followed by the infiltration of monocytes/macrophages and appeared to sustain further blood vessel formation. The disruption of inflammatory cell influx by 2 mechanistically distinct anti-inflammatory drugs, cortisone and ibuprofen, significantly inhibited angiogenesis, indicating a functional involvement of these inflammatory cells in new blood vessel development. A direct addition of isolated heterophils or purified chMMP-9 into the HT-1080 onplants engrafted into cortisone- or ibuprofen-treated embryos reversed the antiangiogenic effects of the drugs. The exogenously added heterophils induced in vivo a further infiltration of endogenous heterophils and monocytes and dramatically rescued the impaired angiogenesis, highlighting the importance of early inflammatory leukocytes in tumor-induced angiogenesis. Moreover, purified heterophils incorporated into onplants lacking growth factors or tumor cells induced angiogenesis in nontreated embryos, further indicating a direct proangiogenic role for neutrophil-like leukocytes.

scholarly journals Partial Decellularized Scaffold Combined with Autologous Nasal Epithelial Cell Sheet for Tracheal Tissue Engineering

2021 ◽  
Vol 22 (19) ◽  
pp. 10322
Author(s):  
Luong Huu Dang ◽  
Shih-Han Hung ◽  
Yuan Tseng ◽  
Ly Xuan Quang ◽  
Nhi Thao Ngoc Le ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Sheet ◽  
Rabbit Model ◽  
Immunohistochemical Analysis ◽  
Airway Epithelial ◽  
Potential Solution ◽  
Cell Sheets ◽  
Cell Sheet Engineering ◽  
Nasal Epithelial Cell

Decellularization has emerged as a potential solution for tracheal replacement. As a fully decellularized graft failed to achieve its purposes, the de-epithelialization partial decellularization protocol appeared to be a promising approach for fabricating scaffolds with preserved mechanical properties and few immune rejection responses after transplantation. Nevertheless, a lack of appropriate concurrent epithelialization treatment can lead to luminal stenosis of the transplant and impede its eventual success. To improve re-epithelialization, autologous nasal epithelial cell sheets generated by our cell sheet engineering platform were utilized in this study under an in vivo rabbit model. The newly created cell sheets have an intact and transplantable appearance, with their specific characteristics of airway epithelial origin being highly expressed upon histological and immunohistochemical analysis. Subsequently, those cell sheets were incorporated with a partially decellularized tracheal graft for autograft transplantation under tracheal partial resection models. The preliminary results two months post operation demonstrated that the transplanted patches appeared to be wholly integrated into the host trachea with adequate healing of the luminal surface, which was confirmed via endoscopic and histologic evaluations. The satisfactory result of this hybrid scaffold protocol could serve as a potential solution for tracheal reconstructions in the future.

Abstract 112: Microrna-532-5p Protects the Mouse Heart Against Myocardial Infarction by Repressing a Positive Regulator of Endothelial-to-mesenchymal Transition, Prss23

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Ahmed S Bayoumi ◽  
Jian P Teoh ◽  
Il-man Kim
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cell ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Locked Nucleic Acid ◽  
Mouse Heart ◽  
Intramyocardial Injection ◽  
Mesenchymal Transition ◽  
Endothelial To Mesenchymal Transition

Myocardial infarction (MI) leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after MI has been identified as a critical event in this process. MicroRNAs (miRs), negative regulators of gene expression, have emerged as important players in heart diseases including MI. We previously showed that miR-532-5p (miR-532) is up-regulated by the β-arrestin-biased β-blocker carvedilol (Carv), which activates protective pathways in the heart independent of G protein-mediated second messenger signaling (Figure A-B). Here, we test whether a β2-adrenergic receptor (β2AR)/β-arrestin-responsive miR, miR-532 functions as a cardioprotective miR against MI. Using cultured cardiac endothelial cell (CEC) and in vivo approaches in mice, we demonstrate that knockdown of miR-532 induces CEC apoptosis when subjected to simulated ischemia-reperfusion. In vivo blocking of miR-532 via intramyocardial injection of its locked nucleic acid-anti-miR results in post-MI abnormalities in cardiac function and remodeling. Mechanistically, miR-532 promotes cardiac vascularization after MI in part by repressing a predicted target, Prss23 and subsequently activating endothelial cell markers such as CD-31 (Figure C). Prss23, which is a vascular protease and modulates Snail transcription to promote endothelial-to-mesenchymal transition (EndoMT), is also down-regulated by Carv in mouse hearts. In conclusion, our novel findings indicate that miR-532-Prss23 axis acts as an important regulator of CEC function during MI and can be suitable for therapeutic intervention in the setting of ischemic heart disease.

Abstract 331: Mir-433 Controls Cardiac Fibrosis

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Lichan Tao ◽  
Xiaoting Wu ◽  
Ping Chen ◽  
Shanshan Li ◽  
Xiaomin Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Mice Model ◽  
Ki 67 ◽  
End Stage ◽  
Common Manifestation

Background: Cardiac fibrosis, a result of multiple injurious insults in heart, is a final common manifestation of chronic heart diseases and can lead to end-stage cardiac failure. MicroRNAs (miRNAs, miRs) participate in many essential biological processes and their dysfunction has been implicated in a variety of cardiovascular diseases including fibrosis. miR-433 has recently been implicated in renal fibrosis, however, its role in cardiac fibrosis is unclear. Methods and results: miR-433 was increased in heart samples from dilated cardiomyopathy patients as determined by qRT-PCRs. In addition, miR-433 was also consistently upregulated in mice model of cardiac fibrosis after myocardial infarction or heart failure. Additionally, miR-433 was found to be enriched in fibroblasts compared to cardiomyocytes. In neonatal cardiac fibroblasts, forced expression of miR-433 promoted cell proliferation as indicated by EdU and Ki-67 staining. Moreover, miR-433 overexpression promoted the transdifferentiation of fibroblasts into myofibroblasts as determined by qRT-PCR and western blot for α-SMA and collagen whether in the presence of TGF-β or not, indicating that miR-433 is sufficient to induce fibrosis. In addition, knockdown of miR-433 inhibited proliferation and the transdifferentiation into myofibroblasts, indicating that miR-433 is required for cardiac fibrosis. Interestingly, miR-433 did not affect the migration of cardiac fibroblast. Importantly, miR-433 antagomir could partially attenuate cardiac fibrosis induced by myocardial infarction in mice. Conclusion: both in vitro and in vivo. Inhibition of miR-433 represents a novel therapeutic strategy for cardiac fibrosis.

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