Jin P.,Wenzhou Medical College |
Zhang X.,Wenzhou Medical College |
Wu Y.,Wenzhou Medical College |
Li L.,Wenzhou Medical College |
And 4 more authors.
Transplantation Proceedings | Year: 2010
Background Diabetes has been widely recognized as a major risk factor for cardiovascular disease. With the development of the regenerative medicine, autologous bone marrow-derived mesenchymal stem cells (BMSCs), transplantation can effectively improve cardiac function after myocardial infarction. However, the BMSCs used in most previous studies are derived from young or normal donors. Little is know about the biological characters change of BMSCs in diabetes mellitus. Methods BMSCs were taken from the streptozotocin (STZ)-induced diabetic rats and normal control rats. Cell proliferation was evaluated by CCK-8 assay. Production of vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-1 were measured by enzyme-linked immunosorbent assay. Apoptosis under hypoxia and serum deprivation culture conditions were detected by Hoechst 33342 stain and flow cytometry. Myogenic differentiation, induced by 5-azacytidine was assessed by using immunocytochemical staining for the expression of sarcomeric α-actin and desmin. Results Diabetic rat models were successfully induced by intraperitoneal injection of STZ. The proliferative abilities of BMSCs derived from diabetic rats decreased significantly compared with that from normal rats (P < .05). Similar results were also presented in the cytokines (VEGF and IGF-1) release (P = .02 and P < .01, respectively) that the ability of antiapoptosis and myogenic differentiation decreased obviously between diabetes group and the normal control group (P < .01). Conclusion BMSCs from STZ-induced diabetic rats could be successfully harvested and expanded in vitro culture condition; their morphology was very similar to normal control group, with minor changes. However, the proliferative and differentiation properties of diabetic BMSCs, as well as cytokine release and antiapoptosis ability, were significantly impaired. © 2010 by Elsevier Inc. All rights reserved. Source
Yang Z.,Chinese Academy of Sciences |
Yang Z.,Research Center for Cardiac Regenerative Medicine |
Wu Y.,Chinese Academy of Sciences |
Wu Y.,Research Center for Cardiac Regenerative Medicine |
And 11 more authors.
Photomedicine and Laser Surgery | Year: 2011
Objectives: Low-level laser irradiation (LLLI) has the potential of exerting cardioprotective effect following myocardial infarction (MI). The authors hypothesized that LLLI could influence the expression of cardiac cytokines and contribute to the reversal of ventricular remodeling. Background: LLLI regulates the expression of cytokines after tissue damage. However, little is known concerning the alteration of the cardiac cytokine expression profile after LLLI. Methods: MI was created by coronary ligation. The surviving rats were divided randomly into laser and control groups. 33 rats were exposed to a diode laser (635 nm, 5 mW, CW, laser, beam spot size 0.8 cm2, 6 mW/cm2, 150 sec, 0.8 J, 1J/cm2) as laser group. Another 33 rats received only coronary ligation and served as control group. 28 rats received a thoracotomy without coronary ligation (sham group). One day after laser irradiation, 5 rats from each group were sacrificed and the heart tissues were analyzed by cytokine antibody arrays. Enzyme-linked immunosorbent assay (ELISA) was performed to confirm its reliability. Two weeks after MI, cardiac function and structure were evaluated by echocardiography and histological study. Results: Cytokine antibody array indicated 4 cytokines were significantly changed after laser therapy. ELISA confirmed that granulocyte-macrophage colony stimulating factor and fractalkine were the cytokines involved in the response to therapeutic laser irradiation. However, there was no difference in cytokine release between various groups at 2 weeks after MI. Although LLLI did not improve the damaged heart function, it did reduce the infarct area expansion. Conclusions: The antibody-based protein array technology was applied for screening the cytokine expression profile following MI, with or without laser irradiation. The expression of multiple cytokines was regulated in the acute phase after LLLI. Our results revealed a potential novel mechanism for applying laser therapy to the treatment of heart disease. Copyright 2011, Mary Ann Liebert, Inc. Source
Wang J.,Chinese Academy of Sciences |
Wang J.,Research Center for Cardiac Regenerative Medicine |
Wang J.,Wenzhou Medical College |
Huang W.,Chinese Academy of Sciences |
And 15 more authors.
Stem Cells and Development | Year: 2012
The enhanced proliferation of mesenchymal stem cells (MSCs) can be helpful for the clinical translation of cell therapy. Low-level laser irradiation (LLLI) has been demonstrated as regulating MSC proliferation. MicroRNAs (miRNAs) are involved in various pathophysiologic processes in stem cells, but the role of miRNAs in the LLLI-based promotion of MSC proliferation remains unclear. We found that the proliferation level and cell cycle-associated genes in MSCs were increased after LLLI treatment in a time-dependent manner. Microarray assays revealed subsets of miRNAs to be differentially regulated, and these dynamic changes were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) after LLLI. miR-193 was the most highly up-regulated miRNA, and the change in it was related with the proliferation level. Gain-loss function experiments demonstrated that miR-193 could regulate the proliferation of MSCs, including human's and rat's, but could not affect the apoptosis and differentiation level. Blockade of miR-193 repressed the MSC proliferation induced by LLLI. By qRT-PCR, we found that miR-193, in particular, regulated cyclin-dependent kinase 2 (CDK2) expression. Bioinformatic analyses and luciferase reporter assays revealed that inhibitor of growth family, member 5 (ING5) could be the best target of miR-193 to functionally regulate proliferation and CDK2 activity, and the mRNA and protein level of ING5 was regulated by miR-193. Furthermore, the ING5 inhibited by small interfering RNA (siRNA) could up-regulate the proliferation of MSCs and the expression of CDK2. Taken together, these results strongly suggest that miR-193 plays a critical part in MSC proliferation in response to LLLI stimulation, which is potentially amenable to therapeutic manipulation for clinical application. Copyright © 2012, Mary Ann Liebert, Inc. 2012. Source
Wang J.,Peking Union Medical College |
Wang J.,Research Center for Cardiac Regenerative Medicine |
Wang J.,Wenzhou Medical College |
Huang W.,Peking Union Medical College |
And 16 more authors.
Journal of Cellular and Molecular Medicine | Year: 2012
Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure. Although dysregulation of microRNA (miRNA) is involved in various pathophysiological processes in the heart, the role of miRNA in fibrosis regulation after MI is not clear. Previously we observed the correlation between fibrosis and the miR-24 expression in hypertrophic hearts, herein we assessed how miR-24 regulates fibrosis after MI. Using qRT-PCR, we showed that miR-24 was down-regulated in the MI heart; the change in miR-24 expression was closely related to extracellular matrix (ECM) remodelling. In vivo, miR-24 could improve heart function and attenuate fibrosis in the infarct border zone of the heart two weeks after MI through intramyocardial injection of Lentiviruses. Moreover, in vitro experiments suggested that up-regulation of miR-24 by synthetic miR-24 precursors could reduce fibrosis and also decrease the differentiation and migration of cardiac fibroblasts (CFs). TGF-β (a pathological mediator of fibrotic disease) increased miR-24 expression, overexpression of miR-24 reduced TGF-β secretion and Smad2/3 phosphorylation in CFs. By performing microarray analyses and bioinformatics analyses, we found furin to be a potential target for miR-24 in fibrosis (furin is a protease which controls latent TGF-β activation processing). Finally, we demonstrated that protein and mRNA levels of furin were regulated by miR-24 in CFs. These findings suggest that miR-24 has a critical role in CF function and cardiac fibrosis after MI through a furin-TGF-β pathway. Thus, miR-24 may be used as a target for treatment of MI and other fibrotic heart diseases. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source
Zhang H.,Chinese Academy of Sciences |
Zhang H.,Research Center for Cardiac Regenerative Medicine |
Chen H.,Research Center for Cardiac Regenerative Medicine |
Wang W.,Chinese Academy of Sciences |
And 3 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010
Cell transplantation has become an attractive option for cardiac regenerative therapy. However, poor cell survival and extensive redistribution throughout the body can drastically affect the outcome and safety of cell therapy. Although various approaches have been attempted to support the survival and engraftment of implanted cells, we need to apply a new comprehensive strategy by melding the in vitro and in vivo approaches to recondition the cells and infarcted myocardium. Here we summarize our understanding of cell survival and migration after transplantation into the damaged heart. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. Source