Publications by authors named "Shahram Rabbani"

47 Publications

Oxygen-rich Environment Ameliorates Cell Therapy Outcomes of Cardiac Progenitor Cells for Myocardial Infarction.

Mater Sci Eng C Mater Biol Appl 2021 Feb 29;121:111836. Epub 2020 Dec 29.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran. Electronic address:

To some extent, cell therapy for myocardial infarction (MI) has supported the idea of cardiac repair; however, further optimizations are inevitable. Combined approaches that comprise suitable cell sources and supporting molecules considerably improved its effect. Here, we devised a strategy of simultaneous transplantation of human cardiac progenitor cells (CPCs) and an optimized oxygen generating microparticles (MPs) embedded in fibrin hydrogel, which was injected into a left anterior descending artery (LAD) ligating-based rat model of acute myocardial infarction (AMI). Functional parameters of the heart, particularly left ventricular systolic function, markedly improved and reached pre-AMI levels. This functional restoration was well correlated with substantially lower fibrotic tissue formation and greater vascular density in the infarct area. Our novel approach promoted CPCs retention and differentiation into cardiovascular lineages. We propose this novel co-transplantation strategy for more efficient cell therapy of AMI which may function by providing an oxygen-rich microenvironment, and thus regulate cell survival and differentiation.
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http://dx.doi.org/10.1016/j.msec.2020.111836DOI Listing
February 2021

Cartilage tissue engineering using injectable functionalized Demineralized Bone Matrix scaffold with glucosamine in PVA carrier, cultured in microbioreactor prior to study in rabbit model.

Mater Sci Eng C Mater Biol Appl 2021 Jan 27;120:111677. Epub 2020 Oct 27.

Department of Hematology and Cell Therapy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Using 3D model of injectable scaffolds for cartilage tissue engineering is one of the challenges that should be addressed to avoid invasive surgery for treatment. For this purpose, chondrocytes on Demineralized Bone Matrix (DBM) scaffolds functionalized with glucosamine in 20% polyvinyl alcohol (PVA) as a carrier was applied to the micro-bioreactor in-vitro, then the study was continued on in-vivo stage. Scaffold biocompatibility tests were performed and the mechanical and physicochemical properties were studied showing the fact that DBM was functionalized by Glucosamine, scaffold degradation rate was 53% after 720 h and swelling ratio was 2.5 times after 16 h, injectable scaffold demonstrated better mechanical characteristics (P < 0.05) than other concentrations of PVA. Consequently, in-vitro tests, including live-dead imaging resulting in 99% viability after 14 days (P < 0.001), DAPI staining and scanning electron microscope imaging were performed to determine the number and viability of the cells on the scaffold, showing a cells proliferation property of this group compared with the control after 14 days (P < 0.0001), then relative gene expression was evaluated and protein expression was assessed. The overall chondrogenic gene expression improved (P < 0.05) compared to the control (2D culture). Subsequently, the scaffold were loaded with chondrocytes and injected into the cartilage lesion part After 24 weeks of surgery, MRI and immunocytochemistry were performed. Then all outputs proved that the scaffold plus cell group had a significantly higher topological score (P < 0.0001) than other groups compared to normal cartilage. Finally, studies have shown that transplantation of chondrocytes in DBM, polyvinyl alcohol and glucosamine scaffold through one surgical stage improves cartilage lesion and it can be considered as a breakthrough in tissue engineering.
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http://dx.doi.org/10.1016/j.msec.2020.111677DOI Listing
January 2021

MicroRNA‑331 inhibits isoproterenol‑induced expression of profibrotic genes in cardiac myofibroblasts via the TGFβ/smad3 signaling pathway.

Sci Rep 2021 Jan 28;11(1):2548. Epub 2021 Jan 28.

Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Cardiac fibrosis in the failing heart is modulated by activated myofibroblasts, and is a pathology marked by their deposition of extracellular matrix proteins. The TGFβ signaling pathway is important in stimulating fibrosis and therefore seems an attractive new target for anti-fibrotic therapy. The relationship between ncRNAs and TGFβ signaling pathway has been extensively studied. Here, we have provided several lines of evidence to prove that the fibrosis process could be regulated by miR-331 through targeting TGFβ signaling. First, bioinformatics analysis and dual luciferase assay validated a direct interaction between the miR-331 and TGFβ-R1 3'UTR sequence which results in the downregulation of TGFβ signaling pathway. Second, miR-331 expression was inversely related to the expression of a number of genes which are involved in extracellular matrix (ECM) production and deposition processes, both in the in vivo and in vitro fibrosis models. Third, in cultured mouse and human cardiac myofibroblasts (CMyoFbs) under ISO treatment, overexpression of miR-331 decreased the expression level of fibrosis-related genes. Consistently, western blot analysis confirmed that miR-331 overexpression ended in both Smad3 and Col1A1 protein level reduction in mouse cardiac myofibroblasts. Finally, flow cytometry analysis, cyclin D1 and D2 gene expression analysis, and wound-healing assay confirmed the inhibitory effect of miR-331 against cell proliferation and migration in ISO-treated cardiac myofibroblasts. Taken together, accumulative results showed that miR-331 reduced the level of fibrosis-related proteins in cardiac myofibroblasts culture via regulating TGFβ signaling pathway.
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http://dx.doi.org/10.1038/s41598-021-82226-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843612PMC
January 2021

A comprehensive systematic review of photocatalytic degradation of pesticides using nano TiO.

Environ Sci Pollut Res Int 2021 Jan 23. Epub 2021 Jan 23.

Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

This study has systematically reviewed all of the research articles about the photocatalytic degradation of pesticides using titanium dioxide (TiO) nanoparticles (NPs) and ultraviolet (UV) irradiation. Online databases were searched for peer-reviewed research articles and conference proceedings published during 2009-2019, and ultimately 112 eligible articles were included in the review. Fifty-three active ingredients of pesticides and one mixture had been investigated, most of them were organophosphorus (22%), followed by triazine derivatives (11%), chloropyridines (9%), and organochlorines (9%). Sixteen types of TiO with an average photodegradation efficiency of 71% were determined. Based on the type of pesticide and experimental conditions such as irradiation time, the complete photodegradation had been observed. The removal of each group of pesticides has been sufficiently discussed in the article. Effect of experimental conditions on photocatalytic activity has been investigated using linear and polynomial regressions. The strategies to reduce the required energy for this process, doping TiO with metal and non-metal agents, innovative reactor designs, etc., were also discussed. In conclusion, TiO NPs have been successful for degradation of pesticides. Future direction for research incorporates developing and application of heterogeneous doped and immobilized titania having optimized characteristics such as surface area, reactive centers, recombination rate, and phase, and capable to photo-degrade low levels of pesticides residues under solar light in an efficient full-scale size.
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http://dx.doi.org/10.1007/s11356-021-12576-8DOI Listing
January 2021

Vascular endothelial growth factor sustained delivery augmented cell therapy outcomes of cardiac progenitor cells for myocardial infarction.

J Tissue Eng Regen Med 2020 12 8;14(12):1939-1944. Epub 2020 Nov 8.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Cell therapy has become a novel promising approach for improvement of cardiac functional capacity in the instances of ventricular remodeling and fibrosis caused by episodes of coronary artery occlusion and hypoxia. The challenge toward enhancing cell engraftment as well as formation of functional tissue, however, necessitated combinatorial approaches. Here, we complemented human embryonic stem cell-derived cardiac progenitor cell (hESC-CPC) therapy by heparin-conjugated, vascular endothelial growth factor (VEGF)-loaded fibrin hydrogel as VEGF delivery system. Transplantation of these cardiac committed cells along with sustained VEGF release could surpass the cardiac repair effects of each constituent alone in a rat model of acute myocardial infarction. The histological sections of rat hearts revealed improved vascularization as well as inclusion of hESC-CPC-derived cardiomyocytes, endothelial, and smooth muscle cells in host myocardium. Thus, co-transplantation of hESC-CPC and proangiogenic factor by a suitable delivery rate may resolve the shortcomings of conventional cell therapy.
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http://dx.doi.org/10.1002/term.3125DOI Listing
December 2020

Exosomes as a next-generation drug delivery system: An update on drug loading approaches, characterization, and clinical application challenges.

Acta Biomater 2020 09 2;113:42-62. Epub 2020 Jul 2.

Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Exosomes are small nanoparticles secreted by almost all cells and have a well-known role in intercellular communication. They are found in different body fluids and can also be isolated from cell culture media. They contain a natural cargo including various protein and nucleic acid molecules originated from their donor cells. In recent years, exosomes have emerged as a desired drug delivery system. They are believed to provide a targeted delivery of drug molecules, supplemented with their natural function. Furthermore, they have a membranous structure similar to liposomes, and that motivated researchers to apply their previous experience of drug loading into liposomes for exosomes. Herein, we discuss applied methods for the encapsulation of different drugs into exosomes, parameters affecting the incorporation of drug molecules into exosomes, characterization techniques, recent achievements, commercialization challenges and the potential future developments of exosomal drugs. Overall, while the application of exosomes as a drug delivery system is still in its infancy, they are considered to be a new class of natural nanocarriers with great potential for clinical application. Understanding of their key formulation parameters, pharmaceutical properties, in vivo behavior and applicable scale-up production will pave their way to the market. STATEMENT OF SIGNIFICANCE: Details of loading methods, characterization and biopharmaceutical properties of drug-incorporated exosomes are presented. Most parameters affecting encapsulation of drugs into exosomes are mentioned to serve as a guide for future studies in this field. Moreover, challenges on the way of exosomes to the market and clinic are described.
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http://dx.doi.org/10.1016/j.actbio.2020.06.036DOI Listing
September 2020

Development of poly (mannitol sebacate)/poly (lactic acid) nanofibrous scaffolds with potential applications in tissue engineering.

Mater Sci Eng C Mater Biol Appl 2020 May 11;110:110626. Epub 2020 Jan 11.

Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran; Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran. Electronic address:

Developing a biomimetic substrate with intrinsic potential for cell attachment and growth has always been a tissue engineering challenge. In the present research, we successfully fabricated PMS:PLA nanofibrous scaffolds for the first time using electrospinning process by adjusting blending ratios, feed rates and polymer concentrations. A desirable composition was found when homogenous nanofibers with an average fiber diameter of 235 ± 38 nm were achieved at 10% w/v for PMS:PLA 60:40. The scaffolds were then characterized for their microstructure, mechanical strength and elasticity, degradation rate, porosity, wettability and cell/tissue compatibility. Mechanical analysis and degradation behavior of PMS:PLA nanofibrous scaffolds revealed appropriate elasticity, stiffness and strength, as well as degradation rate appropriate for soft tissues. Nitrogen adsorption-desorption analysis discovered that mesoporous nanofibers with enhanced specific surface area were fabricated. Further in vitro and in vivo biocompatibility evaluations revealed enhanced cytocompatibility, proliferation and tissue responses of PMS:PLA nanofibrous scaffolds with desirable cell-scaffold interactions. Moreover, PMS:PLA nanofibrous scaffolds exhibited negligible inflammatory responses with significantly thinner fibrotic capsule formation and minor infiltration of inflammatory cells compared to PLA nanofibers. These findings suggest that PMS/PLA nanofibrous scaffolds could be introduced as potential candidates with improved properties for soft tissue engineering applications.
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http://dx.doi.org/10.1016/j.msec.2020.110626DOI Listing
May 2020

Mesenchymal stem cell-derived extracellular vesicles alone or in conjunction with a SDKP-conjugated self-assembling peptide improve a rat model of myocardial infarction.

Biochem Biophys Res Commun 2020 04 10;524(4):903-909. Epub 2020 Feb 10.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran. Electronic address:

Purpose: The aim of this study was to investigate the cardiac repair effect of human bone marrow mesenchymal stromal cells-derived extracellular vesicles (MSC-EVs) after intramyocardial injection in free form or encapsulated within a self-assembling peptide hydrogel modified with SDKP motif, in a rat model of myocardial infarction (MI).

Methods: MSC-EVs were isolated by ultracentrifuge and characterized for physical parameters and surface proteins. Furthermore, cellular uptake and cardioprotective effects of MSC-EVs were evaluated in vitro using neonatal mouse cardiomyocytes (NMCMs). In vivo effects of MSC-EVs on cardiac repair were studied in rat MI model by comparing the vehicle group (injected with PBS), EV group (injected with MSC-EVs) and Gel + EV group (injected with MSC-EVs encapsulated in (RADA)-SDKP hydrogel) with respect to cardiac function and fibrotic area using echocardiography and Masson's trichrome staining, respectively. Histological sections were assessed by α-SMA and CD68 immunostaining to investigate the angiogenic and anti-inflammatory effects of the MSC-EVs.

Results: We observed the uptake of MSC-EVs into NMCMs which led to NMCMs protection against HO-induced oxidative stress by substantial reduction of apoptosis. In myocardial infarcted rats, cardiac function was improved after myocardial injection of MSC-EVs alone or in conjunction with (RADA)-SDKP hydrogel. This functional restoration coincided with promotion of angiogenesis and decrement of fibrosis and inflammation.

Conclusion: These data demonstrated that MSC-EVs can be used alone as a potent therapeutic agent for improvement of myocardial infarction.
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http://dx.doi.org/10.1016/j.bbrc.2020.02.009DOI Listing
April 2020

A Cell-Free SDKP-Conjugated Self-Assembling Peptide Hydrogel Sufficient for Improvement of Myocardial Infarction.

Biomolecules 2020 01 30;10(2). Epub 2020 Jan 30.

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 1665659911, Iran.

Biomaterials in conjunction with stem cell therapy have recently attracted attention as a new therapeutic approach for myocardial infarction (MI), with the aim to solve the delivery challenges that exist with transplanted cells. Self-assembling peptide (SAP) hydrogels comprise a promising class of synthetic biomaterials with cardiac-compatible properties such as mild gelation, injectability, rehealing ability, and potential for sequence modification. Herein, we developed an SAP hydrogel composed of a self-assembling gel-forming core sequence (RADA) modified with SDKP motif with pro-angiogenic and anti-fibrotic activity to be used as a cardioprotective scaffold. The RADA-SDKP hydrogel was intramyocardially injected into the infarct border zone of a rat model of MI induced by left anterior descending artery (LAD) ligation as a cell-free or a cell-delivering scaffold for bone marrow mesenchymal stem cells (BM-MSCs). The left ventricular ejection fraction (LVEF) was markedly improved after transplantation of either free hydrogel or cell-laden hydrogel. This cardiac functional repair coincided very well with substantially lower fibrotic tissue formation, expanded microvasculature, and lower inflammatory response in the infarct area. Interestingly, BM-MSCs alone or in combination with hydrogel could not surpass the cardiac repair effects of the SDKP-modified SAP hydrogel. Taken together, we suggest that the RADA-SDKP hydrogel can be a promising cell-free construct that has the capability for functional restoration in the instances of acute myocardial infarction (AMI) that might minimize the safety concerns of cardiac cell therapy and facilitate clinical extrapolation.
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http://dx.doi.org/10.3390/biom10020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072713PMC
January 2020

Electrochemical-Based Biosensors: New Diagnosis Platforms for Cardiovascular Disease.

Curr Med Chem 2020 ;27(15):2550-2575

Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.

One of the major reasons for mortality throughout the world is cardiovascular diseases. Therefore, bio-markers of cardiovascular disease are of high importance to diagnose and manage procedure. Detecting biomarkers provided a promising procedure in developing bio-sensors. Fast, selective, portable, accurate, inexpensive, and sensitive biomarker sensing instruments will be necessary for detecting and predicting diseases. One of the cardiac biomarkers may be ordered as C-reactive proteins, lipoprotein-linked phospho-lipase, troponin I or T, myoglobin, interleukin-6, interleukin-1, tumor necrosis factor alpha, LDL and myeloperoxidase. The biomarkers are applied to anticipate cardio-vascular illnesses. Initial diagnoses of these diseases are possible by several techniques; however, they are laborious and need costly apparatus. Current researches designed various bio-sensors for resolving the respective issues. Electrochemical instruments and the proposed bio-sensors are preferred over other methods due to its inexpensiveness, mobility, reliability, repeatability. The present review comprehensively dealt with detecting biomarkers of cardiovascular disease through electro-chemical techniques.
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http://dx.doi.org/10.2174/0929867326666191024114207DOI Listing
August 2020

Targeted and Controlled Drug Delivery to a Rat Model of Heart Failure Through a Magnetic Nanocomposite.

Ann Biomed Eng 2020 Feb 6;48(2):709-721. Epub 2019 Nov 6.

Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

As a novel cardiac myosin activator, Omecamtive Mecarbil (OM) has shown promising results in the management of systolic heart failure in clinical examinations. However, the need for repeated administration along with dose-dependent side effects made its use elusive as a standard treatment for heart failure (HF). We hypothesized that improved cardiac function in systolic HF models would be achieved in lower doses by targeted delivery of OM to the heart. To test this hypothesis, a nanocomposite system was developed by composing chitosan and a magnetic core (FeO), loaded with OM, and directed toward the rats' heart via a 0.3 T magnet. HF-induced rats were injected with saline, OM, and OM-loaded nanocomposite (n = 8 in each group) and compared with a group of healthy animals (saline injected, n = 8). Knowing the ejection fraction (EF) of healthy (93.68 ± 1.37%) and HF (71.7 ± 1.41%) rats, injection of nanocomposites was associated with improved EF (EF = 89.6 ± 1.40%). Due to increased heart targeting of nanocomposite (2.5 folds), improved cardiac function was seen with only 4% of the OM dose required for infusion, while injecting the same dose of OM without targeting was unable to stop HF progression (EF = 55.33 ± 3.16%) during 7 days. In conclusion, heart nanocomposites targeting improves the EF by up to 18% by only using 4% of the doses traditionally used in treating the HF.
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http://dx.doi.org/10.1007/s10439-019-02394-yDOI Listing
February 2020

Green formulation of curcumin loaded lipid-based nanoparticles as a novel carrier for inhibition of post-angioplasty restenosis.

Mater Sci Eng C Mater Biol Appl 2019 Dec 30;105:110037. Epub 2019 Jul 30.

Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Restenosis is one of the major complications affecting outcomes of percutaneous coronary interventions. The aims of this study were to formulate curcumin (CUR) nanoparticles by using only lipidic ingredients in the absence of any organic solvent and to determine key formulation parameters using 2-level factorial design. CUR nanoparticles were prepared using triglyceride and egg phosphatidylcholine (EPC) by high-pressure homogenization (HPH) and fully characterized regarding drug loading, particle size, zeta potential, stability, drug release profile, conductivity, viscosity, refractive index, stability, morphology and FTIR analysis. The efficacy of CUR nanoparticles in inhibiting restenosis was investigated in a rat carotid artery model. Balloon-injured rats were randomly assigned to two control (saline and empty carrier) groups and CUR nanoparticle treated group. Arterial restenosis was assessed by histomorphometric, immunohistochemical and CT angiography analyses. Optimized CUR nanoparticles with almost 70% drug entrapment, an average particle size of 58 nm, PDI < 0.2, spherical nanostructures and sustained release profile were prepared. In morphometric analysis, neointimal area and neointima/media ratio significantly decreased in the animal group received CUR nanoparticles compared with control groups. Expression of Ki67 was markedly lower in the CUR nanoformulation group. CT angiograms confirmed patency of the artery in this group. These results suggest that the new strategy of intramural delivery of CUR lipid-based nanoparticles can be considered as a novel approach to prevent neointimal hyperplasia.
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http://dx.doi.org/10.1016/j.msec.2019.110037DOI Listing
December 2019

Functional biological pacemaker generation by T-Box18 protein expression via stem cell and viral delivery approaches in a murine model of complete heart block.

Pharmacol Res 2019 03 21;141:443-450. Epub 2019 Jan 21.

Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Tehran, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Tehran, Iran; School of Medicine, Mashhad University of Medical Sciences, Tehran, Iran.

Despite recent advances in the treatment of cardiac arrhythmia, the available options are still limited and associated with some complications. Induction of biological pacemakers via Tbx18 gene insertion in the heart tissue has been suggested as a promising therapeutic strategy for cardiac arrhythmia. Following a previous in vitro study reporting the production of Tbx18-expressing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), we aimed to investigate the efficacy of these engineered cells to generate pacemaker rhythms in a murine model of complete heart block. We also attempted to generate a functional pacemaker by Tbx18 overexpression in native cardiac cells of rat heart. The hiPSC-derived pacemaker cells were produced by lentiviral delivery of Tbx18 gene to stem cells during a small molecule-based differentiation process. In the present study, 16 male albino Wistar rats were randomly assigned to Tbx18-lentivirus (n = 4) and Tbx18-pacemaker cells (n = 4) administered via injection into the left ventricular anterolateral wall. The control rats received GFP-lentiviruses (n = 4) and GFP-pacemaker cells (n = 4). Fourteen days after the injection, the rats were sacrificed and analyzed by electrocardiography (ECG) recording using a Langendorff-perfused heart model following complete heart block induced by hypokalemia and crashing. Immunofluorescence staining was used to investigate the expression of Tbx18, HCN4 and connexin 43 (Cx43) proteins in Tbx18-delivered cells of heart tissues. The heart rate was significantly reduced after complete heart block in all of the experimental rats (P < 0.05). Heart beating in the Tbx18-transduced hearts was slower compared with rats receiving Tbx18-pacemaker cells (P = 0.04). The duration of ventricular fibrillation (VF) was higher in the lentiviral Tbx18 group compared with the GFP-injected controls (P = 0.02) and the Tbx18-pacemaker cell group (P = 0.02). The ECG recording data showed spontaneous pacemaker rhythms in both intervention groups with signal propagation in Tbx18-transduced ventricles. Immunostaining results confirmed the overexpression of HCN4 and downregulation of Cx43 as a result of the expression of the Tbx18 gene and spontaneously contracting myocyte formation. We confirmed the formation of a functional pacemaker after introduction of Tbx18 via cell and gene therapy strategies. Although the pacemaker activity was better in gene-received hearts since there were longer VF duration and signal propagation from the injection site, more data should be gathered from the long-term activity of such pacemakers in different hosts.
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http://dx.doi.org/10.1016/j.phrs.2019.01.034DOI Listing
March 2019

Cardiovascular stents: overview, evolution, and next generation.

Prog Biomater 2018 Sep 10;7(3):175-205. Epub 2018 Sep 10.

Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, North Kargar, Tehran, Iran.

Compared to bare-metal stents (BMSs), drug-eluting stents (DESs) have been regarded as a revolutionary change in coronary artery diseases (CADs). Releasing pharmaceutical agents from the stent surface was a promising progress in the realm of cardiovascular stents. Despite supreme advantages over BMSs, in-stent restenosis (ISR) and long-term safety of DESs are still deemed ongoing concerns over clinically application of DESs. The failure of DESs for long-term clinical use is associated with following factors including permanent polymeric coating materials, metallic stent platforms, non-optimal drug releasing condition, and factors that have recently been supposed as contributory factors such as degradation products of polymers, metal ions due to erosion and degradation of metals and their alloys utilizing in some stents as metal frameworks. Discovering the direct relation between stent materials and associating adverse effects is a complicated process, and yet it has not been resolved. For clinical success it is of significant importance to optimize DES design and explore novel strategies to overcome all problems including inflammatory response, delay endothelialization, and sub-acute stent thrombosis (ST) simultaneously. In this work, scientific reports are reviewed particularly focusing on recent advancements in DES design which covers both potential improvements of existing and recently novel prototype stent fabrications. Covering a wide range of information from the BMSs to recent advancement, this study mostly sheds light on DES's concepts, namely stent composition, drug release mechanism, and coating techniques. This review further reports different forms of DES including fully biodegradable DESs, shape-memory ones, and polymer-free DESs.
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http://dx.doi.org/10.1007/s40204-018-0097-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173682PMC
September 2018

Simultaneous Delivery of Wharton's Jelly Mesenchymal Stem Cells and Insulin-Like Growth Factor-1 in Acute Myocardial Infarction.

Iran J Pharm Res 2018 ;17(2):426-441

Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences,Tehran,Iran.

Wharton's jelly mesenchymal stem cells (HWJMSCs) hold promise for myocardial regeneration, but optimal treatment regimen (preferably with a growth factor) is required to maximize functional benefits. The aim of this study was to explore the cardioprotective and angiogenesis effects of HWJMSCs combined with insulin-like growth factor-1 (IGF-1) in the treatment of acute myocardial infarction. The hydrogel consisted of Polyethylene glycol (PEG) and hyaluronic acid was prepared and characterized with regards to rheology, morphology, swelling, degradation, and release behaviors. To examine effects, the hydrogels containing HWJMSCs either alone (Cells/hydrogel group) or with IGF-1 (Cells/hydrogel/IGF-1 group) were intra-myocardially injected into a rabbit myocardial infarction model. efficacy was evaluated histological, immunohistochemical, echocardiography, scanning electron microscopy, and SPECT analyses. Eight weeks after infusion, the Cells/hydrogel and Cells/hydrogel/IGF-1 groups exhibited significantly increased left ventricular ejection fraction by echocardiography. Percent of ejection fraction was respectively 18.5% and 40% greater than control ( < 0.01). Vascular density (CD31 positive cells) of both treatment groups were more than the control group and this superiority was more remarkable in Cells/hydrogel/IGF-1 group. Cells/hydrogel/IGF-1 group showed the least defect size in SPECT analysis. Combinatory therapy with HWJMSCs and IGF-1 may additionally improve cardiac function and promote angiogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985162PMC
January 2018

Regenerating Heart Using a Novel Compound and Human Wharton Jelly Mesenchymal Stem Cells.

Arch Med Res 2017 Apr;48(3):228-237

Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Myocardial infarction is a major problem in health system and most conventional therapy is not led to restoration of the health. Stem cell therapy is a method to regenerate the heart but today appropriate cell source and scaffold selection as extracellular matrix to achieve the best effect is disputing.

Aim Of The Study: In this study a combination of human Wharton jelly mesenchymal stem cells (HWJMSCs) with a novel compound consisting polyethylene glycol (PEG), hyaluronic acid and chitosan is presented to heart regeneration.

Methods: After proliferation and expansion of HWJMSCs, these cells were mixed with scaffold and injected into the infarcted rabbit myocardium. After two months cardiac function and infarcted area were evaluated. Immunohistochemistry performed for vessel count and demonstrating of differentiation ability into cardiomyocytes. To confirm this ability PCR was done. Scanning electron microscope was used to evaluate angiogenesis.

Results: Improving cardiac function was higher in cell/scaffold group than the others and it was confirmed by SPECT results which showed least defect size in the myocardium. There were a lot of neoangiogenesis in the target group and also cardiomyogenesis observed in cell/scaffold group. PCR results confirmed the presence of differentiated cardiomyocytes and SEM showed well developed vessel in this group.

Conclusions: Comparing macroscopic and microscopic results between all groups revealed that HWJMSC in combination with this scaffold led to brilliant results regarding cardiac function, angiogenesis and cardiogenesis. It is recommended using these cells and materials for cardiac tissue engineering and regeneration therapy.
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http://dx.doi.org/10.1016/j.arcmed.2017.03.019DOI Listing
April 2017

Effects of Endothelial and Mesenchymal Stem Cells on Improving Myocardial Function in a Sheep Animal Model.

J Tehran Heart Cent 2017 Apr;12(2):65-71

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Myocardial infarction is the main cause of death worldwide. Angiogenesis, a promising new therapy for the treatment of diffuse coronary artery disease, shows a poor response to conventional revascularization techniques. This study focused on improving myocardial function using endothelial cells (ECs) and mesenchymal stem cells (MSCs) in a sheep animal model. Acute myocardial infarction was induced in 18 sheep (12 treated cases and 6 controls). Autologous MSCs and ECs were injected in the infarcted area and the border zone. Two months after transplantation, echocardiography, electron microscopy, and immunohistochemistry were performed. Echocardiography in both MSC and EC groups revealed a significant improvement in the ejection fraction compared with the control group (p value < 0.05). Vascular density, estimated by antibodies against the von Willebrand factor and smooth muscle actin, increased in both study groups. The pattern of vascularity in the MSC and EC groups was diffused. The electron microscopic evaluation of the infracted areas revealed cardiomyocytes in variable stages of development in the border zone in both EC and MSC groups. Both ECs and MSCs were able to promote angiogenesis and improve cardiac function. Presumably, MSCs differentiate into ECs and cause angiogenesis as it occurs for ECs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558057PMC
April 2017

Evaluating the role of autologous mesenchymal stem cell seeded on decellularized pericardium in the treatment of myocardial infarction: an animal study.

Cell Tissue Bank 2017 Dec 20;18(4):527-538. Epub 2017 May 20.

Pediatric Urology and Regenerative Medicine Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, No. 62, Dr. Qarib's Street, Keshavarz Boulevard, Tehran, 1419433151, Iran.

Inappropriate left ventricular remodeling following myocardial infarction (MI) can result in subsequent severe dysfunction. In this study, we tested the hypothesis that decellularized pericardium (DP) or seeded pericardial patch with autologous adipose-derived mesenchymal stem cells (ADMSCs) could be safely used in a MI scar and could improve heart function. Twelve rabbits were randomly divided into three equal groups. Four weeks after MI induction by ligation of the left anterior descending artery in 12 rabbits, animals of G1 (n = 4) received DP patch with labeled ADMSCs. DP patch was implanted in animals of G2 (n = 4). Rabbits of G3 (n = 4) remained without any intervention after MI induction (control group). Serial examinations including echocardiography, electrocardiography (ECG), scanning electron microscopy, histology and immunohistochemistry (IHC) were performed to evaluate the efficacy of the implanted scaffolds on recovery of the infracted myocardium. The results demonstrated that left ventricular contractile function and myocardial pathological changes were significantly improved in rabbits implanted with either DP or ADMSC-seeded pericardium. However, the seeded pericardium was more effective in scar repairing 2 months after the operation, IHC staining with Desmin and CD34 and positive immunofluorescence staining verified the differentiation of ADMSCs to functional cardiomyocytes. This approach may involve the application of autologous ADMSCs seeded on pericardial patch in an attempt to regenerate a contractible myocardium in an animal model of MI.
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http://dx.doi.org/10.1007/s10561-017-9629-2DOI Listing
December 2017

Effective attenuation of vascular restenosis following local delivery of chitosan decorated sirolimus liposomes.

Carbohydr Polym 2017 Feb 9;157:1461-1469. Epub 2016 Nov 9.

Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Assuring the efficient local delivery via biocompatible nanosystems can be considered as a promising therapy for restenosis. The aim of the present study was preparation, in vitro characterization, and in vivo efficacy evaluation of sirolimus containing chitosan decorated liposomes for restenosis treatment. Liposomes were coated with chitosan, leading to ∼38nm increase in the particle size and a positive shift in the zeta potential from -1mV to +21mV. Chitosan modification was also confirmed by TEM, increased stability against detergent solubilization, and FTIR analyses. High entrapment efficiency (≥83%) and sustained release behaviors were demonstrated in both coated and uncoated vesicles. Compared to control groups, treatment of balloon injured rats with uncoated and chitosan-coated liposomes (50μg sirolimus) significantly reduced stenosis by 39% and 62%, respectively. The effect was also confirmed by immunohistochemical and in vivo CT angiography imaging studies. Chitosan-coated liposomes could be a novel platform for restenosis treatment.
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http://dx.doi.org/10.1016/j.carbpol.2016.11.021DOI Listing
February 2017

A combined registration and finite element analysis method for fast estimation of intraoperative brain shift; phantom and animal model study.

Int J Med Robot 2017 Dec 4;13(4). Epub 2016 Dec 4.

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Finite element models for estimation of intraoperative brain shift suffer from huge computational cost. In these models, image registration and finite element analysis are two time-consuming processes.

Methods: The proposed method is an improved version of our previously developed Finite Element Drift (FED) registration algorithm. In this work the registration process is combined with the finite element analysis. In the Combined FED (CFED), the deformation of whole brain mesh is iteratively calculated by geometrical extension of a local load vector which is computed by FED.

Results: While the processing time of the FED-based method including registration and finite element analysis was about 70 s, the computation time of the CFED was about 3.2 s. The computational cost of CFED is almost 50% less than similar state of the art brain shift estimators based on finite element models.

Conclusions: The proposed combination of registration and structural analysis can make the calculation of brain deformation much faster.
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http://dx.doi.org/10.1002/rcs.1792DOI Listing
December 2017

Physicochemical characteristics of liposomes are decisive for their antirestenosis efficacy following local delivery.

Nanomedicine (Lond) 2017 Jan 23;12(2):131-145. Epub 2016 Nov 23.

Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: To develop an ameliorated sirolimus (SIR) liposome for intramural delivery, the effects of various carrier physicochemical parameters on the antirestenosis efficacy were evaluated.

Materials & Methods: Different liposomes were prepared, characterized and administered to balloon injured rats (12 animal groups). Their efficacies were investigated using morphometric, immunohistochemical and in vivo computed tomography imaging analyses.

Results: The antirestenosis efficacy of SIR liposomes decreased in the following order: cationic 100 nm vesicles ≥ cationic 60 nm vesicles > neutral 100 nm vesicles ≥ stealth 100 nm vesicles > anionic 100 nm vesicles. The 100 µg SIR loaded in cationic liposomes showed almost no artery stenosis.

Conclusion: Appropriate modulation of physicochemical characteristics makes it possible to optimize the liposomes for local delivery.
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http://dx.doi.org/10.2217/nnm-2016-0294DOI Listing
January 2017

Antibacterial performance and in vivo diabetic wound healing of curcumin loaded gum tragacanth/poly(ε-caprolactone) electrospun nanofibers.

Mater Sci Eng C Mater Biol Appl 2016 Dec 13;69:1183-91. Epub 2016 Aug 13.

Department of Pathobiology, Faculty of Veterinary Medicine, Karaj Branch, Islamic Azad University, Karaj, Iran.

In this study we describe the potential of electrospun curcumin-loaded poly(ε-caprolactone) (PCL)/gum tragacanth (GT) (PCL/GT/Cur) nanofibers for wound healing in diabetic rats. These scaffolds with antibacterial property against methicillin resistant Staphylococcus aureus as gram positive bacteria and extended spectrum β lactamase as gram negative bacteria were applied in two forms of acellular and cell-seeded for assessing their capability in healing full thickness wound on the dorsum of rats. After 15days, pathological study showed that the application of GT/PCL/Cur nanofibers caused markedly fast wound closure with well-formed granulation tissue dominated by fibroblast proliferation, collagen deposition, complete early regenerated epithelial layer and formation of sweat glands and hair follicles. No such appendage formation was observed in the untreated controls during this duration. Masson's trichrome staining confirmed the increased presence of collagen in the dermis of the nanofiber treated wounds on day 5 and 15, while the control wounds were largely devoid of collagen on day 5 and exhibited less collagen amount on day 15. Quantification analysis of scaffolds on day 5 confirmed that, tissue engineered scaffolds with increased amount of angiogenesis number, granulation tissue area (μ(2)), fibroblast number, and decreased epithelial gap (μ) can be more effective compared to GT/PCL/Cur nanofibers.
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http://dx.doi.org/10.1016/j.msec.2016.08.032DOI Listing
December 2016

Effect of supplementary zinc on orthodontic tooth movement in a rat model.

Dental Press J Orthod 2016 Mar-Apr;21(2):45-50

Dentist, Tehran University of Medical Sciences, Dental Research center, Dentistry Research Institute, Tehran, Iran., Tehran University of Medical Sciences, Tehran University of Medical Sciences, Dental Research center, Dentistry Research Institute, Tehran , Iran.

Introduction: Osteoclasts and osteoblasts are responsible for regulating bone homeostasis during which the trace element zinc has been shown to exert a cumulative effect on bone mass by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption.

Objective: The aim of the present study was to investigate the effects of zinc (Zn) on orthodontic tooth movement (OTM) in a rat model.

Material And Methods: A total of 44 male Wistar rats were divided into four groups of 11 animals each and received 0, 1.5, 20 and 50 ppm Zn in distilled water for 60 days. In the last 21 days of the study, nickel-titanium closed coil springs were ligated between maxillary right incisors and first molars of all rats, and tooth movement was measured at the end of this period. Histological analysis of hematoxylin/eosin slides was performed to assess root resorption lacunae, osteoclast number and periodontal ligament (PDL) width.

Results: Mean OTM was calculated as 51.8, 49.1, 35.5 and 45 µm in the 0, 1.5, 20 and 50 ppm zinc-receiving groups, respectively. There were no significant differences in neither OTM nor histological parameters among the study groups (p > 0.05).

Conclusion: According to the results obtained in the current investigation, increase in supplementary zinc up to 50 ppm does not affect the rate of OTM neither bone and root resorption in rats.
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http://dx.doi.org/10.1590/2177-6709.21.2.045-050.oarDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896281PMC
October 2017

Aortic valve conduit implantation in the descending thoracic aorta in a sheep model: The outcomes of pre-seeded scaffold.

Int J Surg 2016 Apr 24;28:97-105. Epub 2016 Feb 24.

Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.

Background: We evaluated the outcomes of implanting pre-seeded decellularized aortic valve conduit (AVC) with bone marrow-derived mesenchymal stem cells (MSCs) in a sheep model.

Methods: Eight sheep AVCs were obtained under sterile conditions and decellularized by using detergent-based methods. Decellularized AVCs were seeded with autologous bone marrow-derived MSCs in a dynamic bioreactor system. Pre-seeded AVCs were implanted in the descending thoracic aorta in a sheep model. In all sheep, a decellularized pericardial patch was also anastomosed to the proximal part in order to reduce the incidence of rupture. Pathological evaluations, echocardiography, multislice computed tomography (CT), and CT angiography were performed for the evaluation of implanted AVCs.

Results: The longest survival period was 19 months in pre-seeded animals with complete recellularization at the long-term follow-up. Immunohistochemical staining for desmin, smooth muscle actin, and cytokeratin was significantly positive in the pre-seeded samples and reached near normal ranges. CT angiography revealed no intimal tearing after 18 months of follow-up.

Conclusion: Pre-seeded AVCs with bone marrow-derived MSCs may have satisfactory results in postoperative cell seeding capabilities with promising functional potentiality. This modality may be beneficial and may provide a new era of biological grafts in cardiovascular surgery.
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http://dx.doi.org/10.1016/j.ijsu.2016.02.061DOI Listing
April 2016

Effect of novel blend nanofibrous scaffolds on diabetic wounds healing.

IET Nanobiotechnol 2016 Feb;10(1):1-7

Tehran Heart Center, Tehran University of Medical Science, Tehran, Iran.

Chitosan-poly (vinyl alcohol) (Cs: PVA) (2:3) and poly (caprolactone)-chitosan-poly (vinyl alcohol) (PCL: Cs: PVA) (2:1:1.5) nanofibrous blend scaffolds were fabricated using the electrospinning technique in the authors' previous studies. The results of the previous studies confirmed the high biological properties of the scaffolds and their ability in healing of burn and excision wounds on rat model. In the present study, the biological scaffolds were applied on diabetic dorsum skin wounds and diabetic foot wound on rat models (n = 16). Macroscopic and microscopic investigations were carried out using digital images and haematoxylin and eosin (H&E) staining respectively, to measure the wound areas and to track wound healing rate. It was found that at all time points the areas of wounds treated with nanofibrous scaffolds were smaller compared with the controls. Pathological results showed much better healing efficacy for the test samples compared with the control ones. Pathological investigations proved the presence of more pronounced granulation tissues in the scaffold-treated wounds compared with the control ones. At 20 days post excision, the scaffold-treated groups achieved complete repair. The results indicated that Cs: PVA and PCL: Cs: PVA nanofibrous webs could be considered to be promising materials for burn, excision and diabetic wounds healing.
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http://dx.doi.org/10.1049/iet-nbt.2014.0066DOI Listing
February 2016

Anti-hyperlipidemic and anti-atherosclerotic effects of Pinus eldarica Medw. nut in hypercholesterolemic rabbits.

Daru 2015 Jun 9;23:32. Epub 2015 Jun 9.

Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, 4th floor, No 4, Ostad Nejatollahi Street, Engelab Avenue, Tehran, Iran.

Background: Previous studies suggest that chemical constituents present in Pinus eldarica Medw (P. eldarica) nut possess antioxidant properties that may positively influence lipid profile. The present study was conducted to evaluate the efficacy of P. eldarica nut on the experimental atherosclerosis development in hypercholesterolemic rabbits.

Methods: Forty male 6 months old white New Zealand rabbits (1.8-2 kg) were randomly assigned into five equal groups. One group was kept as control (normal) group, fed on standard rabbit diet and other 4 groups were fed on high cholesterol diet (HCD). Out of four HCD groups one group was kept as control (HCD) and other three groups were treated with different doses (50, 100 and 200 mg/kg/day) of P. eldarica nut for 8 weeks. Percentage of aortic wall area changes as indication of atherosclerosis development and fasting blood cholesterol, LDL, HDL and triglyceride levels were determined in all groups.

Results: The results indicate that fasting blood cholesterol and aortic atherosclerotic involvements in 200 mg/kg/day and 100 mg/kg/day P. eldarica nut extract treated groups significantly decreased as compared to the high cholesterol-diet control group.

Conclusion: P. eldarica nut lowers blood cholesterol level and aortic atherosclerotic involvement in hypercholesterolemic rabbits.
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http://dx.doi.org/10.1186/s40199-015-0114-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483207PMC
June 2015

Efficacy of the hatching event in assessing the embryo toxicity of the nano-sized TiO₂ particles in zebrafish: a comparison between two different classes of hatching-derived variables.

Ecotoxicol Environ Saf 2015 Jun 19;116:121-8. Epub 2015 Mar 19.

Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran 14114-13137, Iran.

The aim of the present study was to evaluate the nano-TiO2 toxicity to zebrafish embryos through evaluating the success in hatching in relationship with hours post-exposure instead of considering just the total hatching rate. Zebrafish embryos 4h post-fertilization were exposed to nTiO2 (0, 0.01, 10, and 1000 µg mL(-1)) for 130 h. The hatching rate (HR) was calculated for each concentration (treatment). The HR magnitude was significantly (p<0.001) correlated (using simple regression) to hours post-exposure time interval (hpe; 34, 58, 82, 106, and 130), noted as HR.hpe. The HR descriptive statistics (HRds) and the parameters of the regression models (i.e., constant, x, F, and r(2)) were recruited to define 15 HRds- and 4 h.hpe-derived variables, respectively. The efficacy of the variables was evaluated. Exposure to nTiO2 led to a significant: premature hatching and general decrease in time required for normal hatching; and change in HR and hpe interrelations in a dose-dependent manner. The major change in hatchability between the treatment and control occurred at 58 hpe (62 hpf), when the treatment with nTiO2 induced significant premature hatching compared to only 6% of the hatched embryos in the control at the same time point. EC10 and EC50 values that cause premature hatching at 58 hpe for nTiO2 are 0.073 µg mL(-1) and 107.2 µg mL(-1) respectively. In general(,) this study shows multivariate differences among exposure concentrations of nTiO2 recruiting hatching-derived endpoints.
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http://dx.doi.org/10.1016/j.ecoenv.2015.03.012DOI Listing
June 2015

Tissue engineered poly(caprolactone)-chitosan-poly(vinyl alcohol) nanofibrous scaffolds for burn and cutting wound healing.

IET Nanobiotechnol 2014 Jun;8(2):123-31

Cellular and Molecular Research Center, Iran University of Medical Science, Tehran, Iran.

Natural-synthetic blend nanofibres have recently attracted more interest because of the ability of achieving desirable properties. Poly(ε-caprolactone) (PCL)-chitosan (Cs)-poly(vinyl alcohol) (PVA) blend nanofibrous scaffolds were electrospun in 2:1:1.33 mass ratio of PCL:Cs:PVA. The presence of PCL in the blend leads to improvement in web hydrophobicity and helped the web to retain its integrity in aqueous media. The scaffolds were used in two forms of acellular and with mesenchymal stem cells. They were applied on burn (n = 12) and excisional cutting (n = 12) wounds on dorsum skin of rats. Macroscopic investigations were carried out to measure the wounds areas. It was found that the area of wounds that were treated with cell-seeded nanofibrous scaffolds were smaller compared to other samples. Pathological results showed much better healing performance for cell-seeded scaffolds followed by acellular scaffolds compared with control samples. All these results indicate that PCL:Cs:PVA nanofibrous web would be a proper material for burn and cutting wound healing.
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http://dx.doi.org/10.1049/iet-nbt.2012.0050DOI Listing
June 2014

Dynamic induction of pro-angiogenic milieu after transplantation of marrow-derived mesenchymal stem cells in experimental myocardial infarction.

Int J Cardiol 2014 May 15;173(3):453-66. Epub 2014 Mar 15.

Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (TAIWAN TECH), Taipei, 10607, Taiwan.

Background: Cell-based pro-angiogenic therapy by bone marrow mesenchymal stem cells (MSCs) has been touted as a means to reducing the adverse effects of cardiac remodeling after myocardial infarction (MI). Milieu-dependent regulation of pro-angiogenic potential of MSCs after infarction remains to be elucidated. In this study, the effects of marrow-derived MSCs on the kinetics of angiogenesis signaling factors were investigated in a rabbit model of MI.

Methods: MI was induced in rabbits, and the animals were randomized into two groups (cell transplantation and control, each group with 21 animals). 1 × 10(6) autologous marrow-derived MSCs were injected into the myocardium of the border zone after transfection with a green fluorescent protein (GFP) lentiviral reporter vector. Control animals received PBS vehicle only. Effect of the transplanted cells on the hearts was evaluated over time by pathological, immunofluorescence, western blotting, immuno-electron microscopy, and echocardiographic analyses.

Results: Transplanted GFP-positive MSCs were enriched with time in the peri-infarct border zone with differentiation potential into three major cell types of the heart, including cardiomyocytes, endothelial cells, and smooth muscle cells, and there was significant augmentation of microvascular density. The transplanted cells could change the milieu of the injured myocardium to increase the expression levels of VEGF as well as the ratio of Ang-2 to Ang-1, and to reduce the ratio of phosphorylated Tie2 to Tie2.

Conclusion: An angiogenesis-promoting milieu was induced after the transplantation of marrow MSCs in the injured myocardium. Compared with the resident cells, the transplanted cells had a greater rate of cellular kinetics in the infarcted myocardium.
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http://dx.doi.org/10.1016/j.ijcard.2014.03.008DOI Listing
May 2014

Sirolimus-loaded stealth colloidal systems attenuate neointimal hyperplasia after balloon injury: a comparison of phospholipid micelles and liposomes.

Int J Pharm 2013 Oct 16;455(1-2):320-30. Epub 2013 Jul 16.

Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Restenosis after angioplasty remains a serious complication in clinical cardiology. This study aims to investigate the stealth colloidal systems for local intra-arterial drug delivery. Micelles from polyethylene glycol conjugated with phosphatidylethanolamine and PEGylated liposomes loaded with sirolimus were prepared and characterized with regard to their loading efficiency, particle size distribution, zeta potential, morphology, nuclear magnetic resonance spectroscopy, drug release profile and stability. The antirestenotic effects of the sirolimus-loaded micelles (14 nm) and liposomes (90 nm) were evaluated and compared in the rat carotid injury model following local intravascular delivery. In comparison to control groups, treatment of balloon injured rats with drug loaded micelles and nanoliposomes significantly reduced vascular stenosis by 42% and 19%, respectively (P<0.05). In addition, the luminal area was significantly enlarged by 39% and 60% following treatment with sirolimus-loaded liposomes and micelles, respectively (P<0.05). Immunohistochemistry revealed that sirolimus-loaded nanocarriers suppressed cell proliferation (Ki67-positive cells) as compared to control groups without affecting the density of smooth muscle actin staining. These results suggest that both colloidal nanocarriers could serve as effective intramural drug delivery systems for the treatment of restenosis; however, phospholipid based micelles provided better antirestenotic effects than PEGylated liposomes.
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http://dx.doi.org/10.1016/j.ijpharm.2013.07.003DOI Listing
October 2013