seyed ehsan Enderami - Academia.edu (original) (raw)

Papers by seyed ehsan Enderami

Research paper thumbnail of Epigallocatechin-3-gallate maintains Th1/Th2 response balance and mitigates type-1 autoimmune diabetes induced by streptozotocin through promoting the effect of bone-marrow-derived mesenchymal stem cells

Research paper thumbnail of The differentiation and generation of glucose-sensitive beta like-cells from menstrual blood-derived stem cells using an optimized differentiation medium with platelet-rich plasma (PRP)

Acta histochemica, Apr 1, 2023

Research paper thumbnail of The effect of source animal age, decellularization protocol, and sterilization method on bovine acellular dermal matrix as a scaffold for wound healing and skin regeneration

Artificial Organs, Oct 6, 2022

BackgroundHealing the full‐thickness skin wounds has remained a challenge. One of the most freque... more BackgroundHealing the full‐thickness skin wounds has remained a challenge. One of the most frequently used grafts for skin regeneration is xenogeneic acellular dermal matrices (ADMs), including bovine ADMs. This study investigated the effect of the source animal age, enzymatic versus non‐enzymatic decellularization protocols, and gamma irradiation versus ethylene oxide (EO) sterilization on the scaffold.MethodsADMs were prepared using the dermises of fetal bovine or calf skins. All groups were decellularized through chemical and mechanical methods, unless T‐FADM samples, in which an enzymatic step was added to the decellularization protocol. All groups were sterilized with ethylene oxide (EO), except G‐FADM which was sterilized using gamma irradiation. The scaffolds were characterized through scanning electron microscopy, differential scanning calorimetry, tensile test, MTT assay, DNA quantification, and real‐time PCR. The performance of the ADMs in wound treatment was also evaluated macroscopically and histologically.ResultsAll ADMs were effectively decellularized. In comparison to FADM (EO‐sterilized fetal ADM), morphological, and mechanical properties of G‐FADM, T‐FADM, and CADM (EOsterilized calf ADM) were changed to different extents. In addition, the CADM and G‐FADM were thermally more stable than the FADM and T‐FADM. Although all ADMs were noncytotoxic, the wounds of the FADM, T‐FADM, and G‐FADM groups were contracted to almost 30.0% of the original area on day 7, significantly faster than the CADM (17.5% ± 1.7) and control (12.2% ± 1.59) groups. However, by day 21, all ADMs were mostly closed except for the untreated group (60.1 ± 1.8).ConclusionAltogether, fetal source and EO‐sterilized samples performed better than calf source and gamma‐sterilized samples unless in some mechanical properties. There was no added value in using enzymatic treatment during the decellularization process. Our results suggest that the age, decellularization, and sterilization methods of animal source should be selected based on the clinical requirements.

Research paper thumbnail of Evaluation of hypoxia inducible factor-1 alpha gene expression in colorectal cancer stages of Iranian patients

Journal of Cancer Research and Therapeutics, 2016

Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well kn... more Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. The aim of this study was to analyze the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in a subset of BPV positive equine sarcoids and explore the relationship with vascular endothelial growth factor (VEGF) expression. Results: 80% of equine sarcoids showed strong cytoplasmic staining in >60% of neoplastic fibroblasts, while 20% of samples showed a moderate cytoplasmic staining in 40-60% of neoplastic fibroblasts for HIF-1α. Results of Western blotting (WB) were consistent with immunohistochemistry (IHC). Moreover, a positive correlation between HIF-1α and VEGF expression (r = 0.60, p < 0.01) was observed. Conclusion: we have shown that HIF-1α was strongly expressed in equine sarcoid. The upregulation of HIF-1α has been described in numerous tumors and can be modulated by many proteins encoded by transforming viruses. Thus, it is also possible that BPV could have a relevant role in HIF-1α pathway regulation, contributing to the development of equine sarcoids by promoting HIF-1α/VEGF mediated tumor angiogenesis.

Research paper thumbnail of Generation of high-yield insulin producing cells from human-induced pluripotent stem cells on polyethersulfone nanofibrous scaffold

Artificial Cells Nanomedicine and Biotechnology, Feb 12, 2018

Transplantation of islet is a promising method in treatment of patients with type 1 diabetes mell... more Transplantation of islet is a promising method in treatment of patients with type 1 diabetes mellitus (T1DM), however, is limited by islet shortage. The aim of this study was to prepare a polyethersulfone (PES) nanofibrous scaffolds to evaluate the pancreatic differentiation of human induced pluripotent stem cells (hiPSCs). The differentiation process in tissue culture dishes and PES scaffolds was evaluated at mRNA and protein level by RT-qPCR and immunofluorescence assay, respectively. The functionality of differentiated cells was determined by insulin and C-peptide release in response to glucose challenges. The results of this study showed that cells cultured on PES nanofibrous scaffolds exhibit more pancreatic b-cell characteristics as they express more pancreatic tissue-specific genes and proteins. Furthermore, the immunoassay showed that differentiated cells in both culture plates and PES scaffolds groups are functional and secrete C-peptide and insulin in response to glucose challenges. Altogether, the results of this study demonstrated that PES nanofibrous scaffold could provide the microenvironment that promotes the differentiation of induced pluripotent stem cells (iPSCs) into insulin producing cells.

Research paper thumbnail of Generation of insulin‐producing cells from human adipose‐derived mesenchymal stem cells on PVA scaffold by optimized differentiation protocol

Journal of Cellular Physiology, Dec 26, 2017

Studies on patient‐specific human‐induced pluripotent stem cells (hiPSCs) as well as a series of ... more Studies on patient‐specific human‐induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet‐rich plasma (PRP) that induce the hiPSCs into insulin‐producing cells (IPCs). We present here a differentiation protocol consisting of five stages in two groups including protocol with PRP and without PRP. Charac­teristics of derived IPCs in both groups were evaluated at the mRNA and protein levels, cell cycle and viability in the end stage of cell differentiation. The in vitro studies indicated the treatment of hiPSCs in the protocol with PRP resulting in differentiated cells with strong characteristics of IPCs including islet‐like cells, the expression of mature and functional pancreatic beta cell specific marker genes. In addition to these pancreatic specific markers were detected by immunochemistry and Western blot. Our differentiated cells in two groups secreted insulin and C‐peptide in a glucose stimulation test by ELISA showing in vitro functional. The results of the cell cycle assay confirmed that differentiation has been done. We reported for the first time that PRP might be ideal additive in the culture medium to induce pancreatic differentiation in the hiPSCs. This study provides a new approach to investigate the role of PRP in pancreatic differentiation protocols and enhance the feasibility of using patient‐specific iPSCs and autologous PRP for future beta cells replacement therapies for T1DM. J. Cell. Physiol. 232: 2878–2886, 2017. © 2016 Wiley Periodicals, Inc.

Research paper thumbnail of Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells into Insulin-Producing Beta Cells with the Enhanced Functional Level on Electrospun PRP-PVP-PCL/PCL Nanofibers Scaffold

Cell transplantation strategies have provided potential therapeutic approaches for treatment of n... more Cell transplantation strategies have provided potential therapeutic approaches for treatment of neurodegenerative diseases. Mesenchymal stem cells from Wharton's jelly (WJMSCs) are abundant and available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in the future. However, MSC transplantation without any induction or support material causes poor control of cell viability and differentiation. In this study, we investigated the effect of the nanoscaffolds on WJMSCs differentiation into motor neuronal lineages in the presence of retinoic acid (RA) and sonic hedgehog (Shh). Surface properties of scaffolds have been shown to significantly influence cell behaviors such as adhesion, proliferation, and differentiation. Therefore, polycaprolactone (PCL) nanofibers were constructed via electrospinning, surface modified by plasma treatment, and grafted by collagen. Characterization of the scaffolds by means of ATR-FTIR, contact angel, and Bradford proved grafting of the collagen on the surface of the scaffolds. WJMSCs were seeded on nanofibrous and tissue culture plate (TCP) and viability of WJMSCs were measured by MTT assay and then induced to differentiate into motor neuron-like cells for 15 days. Differentiated cells were evaluated morphologically, and real-time PCR and immunocytochemistry methods were done to evaluate expression of motor neuron-like cell markers in mRNA and protein levels. Our results showed that obtained cells could express motor neuron biomarkers at both RNA and protein levels, but the survival and differentiation of WJMSCs into motor neuron-like cells on the PCL/collagen scaffold were higher than cultured cells in the TCP and PCL groups. Taken together, WJMSCs are an attractive stem cell source for inducing into motor neurons in vitro especially when grown on nanostructural scaffolds and PCL/collagen scaffolds can provide a suitable, three-dimensional situation for neuronal survival and differentiation that suggest their potential application towards nerve regeneration.

Research paper thumbnail of The use of mesenchymal stem cells in the process of treatment and tissue regeneration after recovery in patients with Covid-19

Gene, Apr 1, 2021

In addition to causing health concerns, the new coronavirus has been considered in the world with... more In addition to causing health concerns, the new coronavirus has been considered in the world with its unknown mechanism of physiopathogenesis and long-term effects after patient recovery. Pulmonary, renal, hepatic and cardiac complications have been reported so far. Beside the researchers' focus on finding vaccines and using conventional therapies, cell-based therapy might be an effective therapeutic strategy. The use of mesenchymal stem cells (MSCs) is one of the options due to their immunomodulatory properties and their proven effects in the treatment of many diseases. As MSCs are not infected with covid-19, there is evidence that it modulates the immune system and prevents the virus from clotting. Despite the beginning of numerous clinical trials in the use of mesenchymal stem cells, it is necessary to set a practical guideline that specifies items such as cell origin, number of cells, frequency of injection, injection site, etc.

Research paper thumbnail of Generation of glucose sensitive insulin‐secreting cells from human induced pluripotent stem cells on optimized polyethersulfone hybrid nanofibrous scaffold

Artificial Organs, Nov 4, 2022

Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells... more Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network.

Research paper thumbnail of Design of a multi-epitope peptide vaccine against SARS-CoV-2 based on immunoinformatics data

Journal of Mazandaran University of Medical Sciences, Nov 10, 2020

Background and purpose: In 2019, the world has witnessed the emergence of a virus that caused acu... more Background and purpose: In 2019, the world has witnessed the emergence of a virus that caused acute respiratory distress syndrome in human with high mortality rates (approximately 3.7%). So far, no effective treatment has been proven against COVID-19. This study aimed at designing a multiepitope vaccine combining several T-cell and B-cell epitopes of the SARS-CoV-2. Materials and methods: Based on immunoinformatics strategies, B-cell and T-cell epitopes were predicted using immune Epitope Database and Analysis Resource (IEDB). Then, the appropriate predicted epitopes were joined to each other by suitable linkers, and the multi-epitope vaccine constructed was suggested as a vaccine candidate against SARS-CoV-2. Results: In this study, 28 B-cell epitopes and 33 T-cell epitopes were predicted. Then, to design the multi epitope vaccine, 5 epitopes were used from the virion surface of spike protein and one epitope was used from intravirion region of the Envelope, Membrane, and Nucleocapsid proteins that later on were joined with flexible glycine linker. Conclusion: Based on the immunoinformatics results obtained, it seems that different epitopes from SARS-CoV-2 structural proteins have high ability to stimulate humoral and cellular immune responses, so the multi-epitope vaccine designed with these epitopes, can help to accelerate the production of effective vaccines against COVID-19.

Research paper thumbnail of Scrophularia striata extract incorporated nanofibrous scaffold improved osteogenic differentiation of mesenchymal stem cells

Journal of Drug Delivery Science and Technology

Research paper thumbnail of The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton’s Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds

Genes

The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not ... more The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular dermal matrix (FADM) in combination with human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) to heal full-thickness skin wounds. FADM was prepared from a 6-month-old trauma-aborted fetus. WJ-MSCs were derived from a human umbilical cord and seeded on the FADM. Rat models of full-thickness wounds were created and divided into three groups: control (no treatment), FADM, and FADM-WJMSCs groups. Wound treatment was evaluated microscopically and histologically on days 7, 14, and 21 post-surgery. The prepared FADM was porous and decellularized with a normal range of residual DNA. WJ-MSCs were seeded and proliferated on FADM effectively. The highest wound closure rate was observed in the FADM-WJMSC group on days 7 and 14 p...

Research paper thumbnail of The differentiation and generation of glucose-sensitive beta like-cells from menstrual blood-derived stem cells using an optimized differentiation medium with platelet-rich plasma (PRP)

Research paper thumbnail of Injectable hydrogels in central nervous system: Unique and novel platforms for promoting extracellular matrix remodeling and tissue engineering

Research paper thumbnail of Enhancement of immunogenicity and neutralizing responses against SARS-CoV-2 spike protein using the Fc fusion fragment

Life Sciences

Vaccination has played an important role in protecting against death and the severity of COVID-19... more Vaccination has played an important role in protecting against death and the severity of COVID-19. The recombinant protein vaccine platform has a long track record of safety and efficacy. Here, we fused the SARS-CoV-2 spike S1 subunit to the Fc region of IgG and investigated immunogenicity, reactivity to human vaccinated sera, and neutralizing activity as a candidate protein vaccine. Materials and method: We evaluated the immunogenicity of CHO-expressed S1-Fc fusion protein and tag-free S1 protein in rabbits via the production of S1-specific polyclonal antibodies. We subsequently compared the neutralizing activities of sera from immunized rabbits and human-vaccinated individuals using a surrogate Virus Neutralization Test (sVNT). Key findings: The results indicate that S1-specific polyclonal antibodies were induced in all groups; however, antibody levels were higher in rabbits immunized with S1-Fc fusion protein than tag-free S1 protein. Moreover, the reactivity of human vaccinated sera against S1-Fc fusion protein was significantly higher than tag-free S1 protein. Lastly, the results of the virus-neutralizing activity revealed that vaccination with S1-Fc fusion protein induced the highest level of neutralizing antibody response against SARS-CoV-2. Significance: Our results demonstrate that the S1 protein accompanied by the Fc fragment significantly enhances the immunogenicity and neutralizing responses against SARS-CoV-2. It is hoped that this platform can be used for human vaccination.

Research paper thumbnail of Mesenchymal Stromal Cells and their EVs as Potential Leads for SARSCoV2 Treatment

Current Stem Cell Research & Therapy

: In December 2019, a betacoronavirus was isolated from pneumonia cases in China and rapidly turn... more : In December 2019, a betacoronavirus was isolated from pneumonia cases in China and rapidly turned into a pandemic of COVID-19. The virus is an enveloped positive-sense ssRNA and causes a severe respiratory syndrome along with a cytokine storm, which is the main cause of most complications. Therefore, treatments that can effectively control the inflammatory reactions are necessary. Mesenchymal Stromal Cells and their EVs are well-known for their immunomodulatory effects, inflammation reduction, and regenerative potentials. These effects are exerted through paracrine secretion of various factors. Their EVs also transport various molecules such as microRNAs to other cells and affect recipient cells' behavior. Scores of research and clinical trials have indicated the therapeutic potential of EVs in various diseases. EVs also seem to be a promising approach for severe COVID-19 treatment. EVs have also been used to develop vaccines since EVs are biocompatible nanoparticles that can be easily isolated and engineered. In this review, we have focused on the use of Mesenchymal Stromal Cells and their EVs for the treatment of COVID-19, their therapeutic capabilities, and vaccine development.

Research paper thumbnail of A novel hybrid polymer of PCL/fish gelatin nanofibrous scaffold improves proliferation and differentiation of Wharton's jelly‐derived mesenchymal cells into islet‐like cells

Artificial Organs

BackgroundUsing a different source of stem cells to compensate for the lost beta cells is a promi... more BackgroundUsing a different source of stem cells to compensate for the lost beta cells is a promising way to cure diabetic patients. Besides, the best efficiency of insulin‐producing cells (IPCs) will appear when we culture them in an environment similar to inside the body. Hence, three‐dimensional (3D) culture ameliorates the differentiation of diverse kinds of stem cells into IPCs compared to those differentiated in two‐dimensional (2D) culture. In this study, we aim to create an ideal differentiation environment by using PCL/Fish gelatin nanofibrous scaffolds to differentiate Wharton's jelly‐derived mesenchymal cells (WJ‐MSCs) to IPCs and compare them with a 2D cultured group.MethodsThe evaluation of cellular, molecular, and functional properties of differentiated cells on the 3D and 2D cultures was investigated by several assays such as electron microscopy, quantitative PCR, immunochemistry, western blotting, and ELISA.ResultsThe in vitro studies showed that WJ‐MSCs differen...

Research paper thumbnail of The use of mesenchymal stem cells in the process of treatment and tissue regeneration after recovery in patients with Covid-19

Gene, 2021

In addition to causing health concerns, the new coronavirus has been considered in the world with... more In addition to causing health concerns, the new coronavirus has been considered in the world with its unknown mechanism of physiopathogenesis and long-term effects after patient recovery. Pulmonary, renal, hepatic and cardiac complications have been reported so far. Beside the researchers' focus on finding vaccines and using conventional therapies, cell-based therapy might be an effective therapeutic strategy. The use of mesenchymal stem cells (MSCs) is one of the options due to their immunomodulatory properties and their proven effects in the treatment of many diseases. As MSCs are not infected with covid-19, there is evidence that it modulates the immune system and prevents the virus from clotting. Despite the beginning of numerous clinical trials in the use of mesenchymal stem cells, it is necessary to set a practical guideline that specifies items such as cell origin, number of cells, frequency of injection, injection site, etc.

Research paper thumbnail of Application of a novel bioreactor for in vivo engineering of pancreas tissue

Journal of cellular physiology, Jan 13, 2017

Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplanta... more Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplantation is an acceptable treatment for native organ failure. However, it is associated with several problems due to a number of reasons, such as the lack of appropriate donors and immunosuppression. In our present study, a novel model is presented for in vivo recellularization of acellular pancreas by implanting between the host pancreas and the adjacent omental flap. In this study, the pancreases were harvested and cannulated via the common bile duct and then, the scaffolds were acellularized by a detergent-based protocol. After that, the abdomens of 35 rats were opened and the spleen was extracted with the adjacent omentum, and placed outside the abdomen. The acellularized scaffold was stretched over the host pancreas and the omentum was wrapped around it to make a sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked with Prolene 4-0 on four sides. All samples...

Research paper thumbnail of Nisin and non-essential amino acids: new perspective in differentiation of neural progenitors from human-induced pluripotent stem cells in vitro

Human cell, 2021

Over the past decades, stem cell therapy has been investigated as a promising approach towards va... more Over the past decades, stem cell therapy has been investigated as a promising approach towards various diseases, including neurodegenerative disorders. Stem cells show the capability to differentiate into neuronal progenitor cells in vitro. In the present study, the differentiation potential of human-induced pluripotent stem cells (hiPSCs) into neural lineages was examined under the efficient induction media containing forskolin and 3-isobutyl-1-methyl-xanthine (IBMX) in the presence of nisin (Ni), non-essential amino acids (NEAA) and combination of those (NEAA-Ni) in vitro. The optimum concentrations of these factors were obtained by MTT assay and acridine orange (AO) staining. The effect of Ni and NEAA on the expression rate of neural-specific markers including NSE, MAP2, and ß-tubulin III was studied via immunocytochemistry (ICC) and real-time RT-PCR analyses. Our results indicated that the induction medium containing Ni or NEAA increased the gene and protein expression of NSE, M...

Research paper thumbnail of Epigallocatechin-3-gallate maintains Th1/Th2 response balance and mitigates type-1 autoimmune diabetes induced by streptozotocin through promoting the effect of bone-marrow-derived mesenchymal stem cells

Research paper thumbnail of The differentiation and generation of glucose-sensitive beta like-cells from menstrual blood-derived stem cells using an optimized differentiation medium with platelet-rich plasma (PRP)

Acta histochemica, Apr 1, 2023

Research paper thumbnail of The effect of source animal age, decellularization protocol, and sterilization method on bovine acellular dermal matrix as a scaffold for wound healing and skin regeneration

Artificial Organs, Oct 6, 2022

BackgroundHealing the full‐thickness skin wounds has remained a challenge. One of the most freque... more BackgroundHealing the full‐thickness skin wounds has remained a challenge. One of the most frequently used grafts for skin regeneration is xenogeneic acellular dermal matrices (ADMs), including bovine ADMs. This study investigated the effect of the source animal age, enzymatic versus non‐enzymatic decellularization protocols, and gamma irradiation versus ethylene oxide (EO) sterilization on the scaffold.MethodsADMs were prepared using the dermises of fetal bovine or calf skins. All groups were decellularized through chemical and mechanical methods, unless T‐FADM samples, in which an enzymatic step was added to the decellularization protocol. All groups were sterilized with ethylene oxide (EO), except G‐FADM which was sterilized using gamma irradiation. The scaffolds were characterized through scanning electron microscopy, differential scanning calorimetry, tensile test, MTT assay, DNA quantification, and real‐time PCR. The performance of the ADMs in wound treatment was also evaluated macroscopically and histologically.ResultsAll ADMs were effectively decellularized. In comparison to FADM (EO‐sterilized fetal ADM), morphological, and mechanical properties of G‐FADM, T‐FADM, and CADM (EOsterilized calf ADM) were changed to different extents. In addition, the CADM and G‐FADM were thermally more stable than the FADM and T‐FADM. Although all ADMs were noncytotoxic, the wounds of the FADM, T‐FADM, and G‐FADM groups were contracted to almost 30.0% of the original area on day 7, significantly faster than the CADM (17.5% ± 1.7) and control (12.2% ± 1.59) groups. However, by day 21, all ADMs were mostly closed except for the untreated group (60.1 ± 1.8).ConclusionAltogether, fetal source and EO‐sterilized samples performed better than calf source and gamma‐sterilized samples unless in some mechanical properties. There was no added value in using enzymatic treatment during the decellularization process. Our results suggest that the age, decellularization, and sterilization methods of animal source should be selected based on the clinical requirements.

Research paper thumbnail of Evaluation of hypoxia inducible factor-1 alpha gene expression in colorectal cancer stages of Iranian patients

Journal of Cancer Research and Therapeutics, 2016

Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well kn... more Background: equine sarcoids are the most frequent skin tumors in equidae worldwide. It is well known that delta bovine papillomaviruses are their causative agents. We have recently shown the presence in equine sarcoids of abnormal vessel structures, which could cause a hypoxic condition. The aim of this study was to analyze the expression of hypoxia-inducible factor-1 alpha (HIF-1α) in a subset of BPV positive equine sarcoids and explore the relationship with vascular endothelial growth factor (VEGF) expression. Results: 80% of equine sarcoids showed strong cytoplasmic staining in >60% of neoplastic fibroblasts, while 20% of samples showed a moderate cytoplasmic staining in 40-60% of neoplastic fibroblasts for HIF-1α. Results of Western blotting (WB) were consistent with immunohistochemistry (IHC). Moreover, a positive correlation between HIF-1α and VEGF expression (r = 0.60, p < 0.01) was observed. Conclusion: we have shown that HIF-1α was strongly expressed in equine sarcoid. The upregulation of HIF-1α has been described in numerous tumors and can be modulated by many proteins encoded by transforming viruses. Thus, it is also possible that BPV could have a relevant role in HIF-1α pathway regulation, contributing to the development of equine sarcoids by promoting HIF-1α/VEGF mediated tumor angiogenesis.

Research paper thumbnail of Generation of high-yield insulin producing cells from human-induced pluripotent stem cells on polyethersulfone nanofibrous scaffold

Artificial Cells Nanomedicine and Biotechnology, Feb 12, 2018

Transplantation of islet is a promising method in treatment of patients with type 1 diabetes mell... more Transplantation of islet is a promising method in treatment of patients with type 1 diabetes mellitus (T1DM), however, is limited by islet shortage. The aim of this study was to prepare a polyethersulfone (PES) nanofibrous scaffolds to evaluate the pancreatic differentiation of human induced pluripotent stem cells (hiPSCs). The differentiation process in tissue culture dishes and PES scaffolds was evaluated at mRNA and protein level by RT-qPCR and immunofluorescence assay, respectively. The functionality of differentiated cells was determined by insulin and C-peptide release in response to glucose challenges. The results of this study showed that cells cultured on PES nanofibrous scaffolds exhibit more pancreatic b-cell characteristics as they express more pancreatic tissue-specific genes and proteins. Furthermore, the immunoassay showed that differentiated cells in both culture plates and PES scaffolds groups are functional and secrete C-peptide and insulin in response to glucose challenges. Altogether, the results of this study demonstrated that PES nanofibrous scaffold could provide the microenvironment that promotes the differentiation of induced pluripotent stem cells (iPSCs) into insulin producing cells.

Research paper thumbnail of Generation of insulin‐producing cells from human adipose‐derived mesenchymal stem cells on PVA scaffold by optimized differentiation protocol

Journal of Cellular Physiology, Dec 26, 2017

Studies on patient‐specific human‐induced pluripotent stem cells (hiPSCs) as well as a series of ... more Studies on patient‐specific human‐induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet‐rich plasma (PRP) that induce the hiPSCs into insulin‐producing cells (IPCs). We present here a differentiation protocol consisting of five stages in two groups including protocol with PRP and without PRP. Charac­teristics of derived IPCs in both groups were evaluated at the mRNA and protein levels, cell cycle and viability in the end stage of cell differentiation. The in vitro studies indicated the treatment of hiPSCs in the protocol with PRP resulting in differentiated cells with strong characteristics of IPCs including islet‐like cells, the expression of mature and functional pancreatic beta cell specific marker genes. In addition to these pancreatic specific markers were detected by immunochemistry and Western blot. Our differentiated cells in two groups secreted insulin and C‐peptide in a glucose stimulation test by ELISA showing in vitro functional. The results of the cell cycle assay confirmed that differentiation has been done. We reported for the first time that PRP might be ideal additive in the culture medium to induce pancreatic differentiation in the hiPSCs. This study provides a new approach to investigate the role of PRP in pancreatic differentiation protocols and enhance the feasibility of using patient‐specific iPSCs and autologous PRP for future beta cells replacement therapies for T1DM. J. Cell. Physiol. 232: 2878–2886, 2017. © 2016 Wiley Periodicals, Inc.

Research paper thumbnail of Differentiation of Wharton's Jelly-Derived Mesenchymal Stem Cells into Insulin-Producing Beta Cells with the Enhanced Functional Level on Electrospun PRP-PVP-PCL/PCL Nanofibers Scaffold

Cell transplantation strategies have provided potential therapeutic approaches for treatment of n... more Cell transplantation strategies have provided potential therapeutic approaches for treatment of neurodegenerative diseases. Mesenchymal stem cells from Wharton's jelly (WJMSCs) are abundant and available adult stem cells with low immunological incompatibility, which could be considered for cell replacement therapy in the future. However, MSC transplantation without any induction or support material causes poor control of cell viability and differentiation. In this study, we investigated the effect of the nanoscaffolds on WJMSCs differentiation into motor neuronal lineages in the presence of retinoic acid (RA) and sonic hedgehog (Shh). Surface properties of scaffolds have been shown to significantly influence cell behaviors such as adhesion, proliferation, and differentiation. Therefore, polycaprolactone (PCL) nanofibers were constructed via electrospinning, surface modified by plasma treatment, and grafted by collagen. Characterization of the scaffolds by means of ATR-FTIR, contact angel, and Bradford proved grafting of the collagen on the surface of the scaffolds. WJMSCs were seeded on nanofibrous and tissue culture plate (TCP) and viability of WJMSCs were measured by MTT assay and then induced to differentiate into motor neuron-like cells for 15 days. Differentiated cells were evaluated morphologically, and real-time PCR and immunocytochemistry methods were done to evaluate expression of motor neuron-like cell markers in mRNA and protein levels. Our results showed that obtained cells could express motor neuron biomarkers at both RNA and protein levels, but the survival and differentiation of WJMSCs into motor neuron-like cells on the PCL/collagen scaffold were higher than cultured cells in the TCP and PCL groups. Taken together, WJMSCs are an attractive stem cell source for inducing into motor neurons in vitro especially when grown on nanostructural scaffolds and PCL/collagen scaffolds can provide a suitable, three-dimensional situation for neuronal survival and differentiation that suggest their potential application towards nerve regeneration.

Research paper thumbnail of The use of mesenchymal stem cells in the process of treatment and tissue regeneration after recovery in patients with Covid-19

Gene, Apr 1, 2021

In addition to causing health concerns, the new coronavirus has been considered in the world with... more In addition to causing health concerns, the new coronavirus has been considered in the world with its unknown mechanism of physiopathogenesis and long-term effects after patient recovery. Pulmonary, renal, hepatic and cardiac complications have been reported so far. Beside the researchers' focus on finding vaccines and using conventional therapies, cell-based therapy might be an effective therapeutic strategy. The use of mesenchymal stem cells (MSCs) is one of the options due to their immunomodulatory properties and their proven effects in the treatment of many diseases. As MSCs are not infected with covid-19, there is evidence that it modulates the immune system and prevents the virus from clotting. Despite the beginning of numerous clinical trials in the use of mesenchymal stem cells, it is necessary to set a practical guideline that specifies items such as cell origin, number of cells, frequency of injection, injection site, etc.

Research paper thumbnail of Generation of glucose sensitive insulin‐secreting cells from human induced pluripotent stem cells on optimized polyethersulfone hybrid nanofibrous scaffold

Artificial Organs, Nov 4, 2022

Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells... more Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network.

Research paper thumbnail of Design of a multi-epitope peptide vaccine against SARS-CoV-2 based on immunoinformatics data

Journal of Mazandaran University of Medical Sciences, Nov 10, 2020

Background and purpose: In 2019, the world has witnessed the emergence of a virus that caused acu... more Background and purpose: In 2019, the world has witnessed the emergence of a virus that caused acute respiratory distress syndrome in human with high mortality rates (approximately 3.7%). So far, no effective treatment has been proven against COVID-19. This study aimed at designing a multiepitope vaccine combining several T-cell and B-cell epitopes of the SARS-CoV-2. Materials and methods: Based on immunoinformatics strategies, B-cell and T-cell epitopes were predicted using immune Epitope Database and Analysis Resource (IEDB). Then, the appropriate predicted epitopes were joined to each other by suitable linkers, and the multi-epitope vaccine constructed was suggested as a vaccine candidate against SARS-CoV-2. Results: In this study, 28 B-cell epitopes and 33 T-cell epitopes were predicted. Then, to design the multi epitope vaccine, 5 epitopes were used from the virion surface of spike protein and one epitope was used from intravirion region of the Envelope, Membrane, and Nucleocapsid proteins that later on were joined with flexible glycine linker. Conclusion: Based on the immunoinformatics results obtained, it seems that different epitopes from SARS-CoV-2 structural proteins have high ability to stimulate humoral and cellular immune responses, so the multi-epitope vaccine designed with these epitopes, can help to accelerate the production of effective vaccines against COVID-19.

Research paper thumbnail of Scrophularia striata extract incorporated nanofibrous scaffold improved osteogenic differentiation of mesenchymal stem cells

Journal of Drug Delivery Science and Technology

Research paper thumbnail of The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton’s Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds

Genes

The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not ... more The treatment of full-thickness skin wounds is a problem in the clinical setting, as they do not heal spontaneously. Extensive pain at the donor site and a lack of skin grafts limit autogenic and allogeneic skin graft availability. We evaluated fetal bovine acellular dermal matrix (FADM) in combination with human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs) to heal full-thickness skin wounds. FADM was prepared from a 6-month-old trauma-aborted fetus. WJ-MSCs were derived from a human umbilical cord and seeded on the FADM. Rat models of full-thickness wounds were created and divided into three groups: control (no treatment), FADM, and FADM-WJMSCs groups. Wound treatment was evaluated microscopically and histologically on days 7, 14, and 21 post-surgery. The prepared FADM was porous and decellularized with a normal range of residual DNA. WJ-MSCs were seeded and proliferated on FADM effectively. The highest wound closure rate was observed in the FADM-WJMSC group on days 7 and 14 p...

Research paper thumbnail of The differentiation and generation of glucose-sensitive beta like-cells from menstrual blood-derived stem cells using an optimized differentiation medium with platelet-rich plasma (PRP)

Research paper thumbnail of Injectable hydrogels in central nervous system: Unique and novel platforms for promoting extracellular matrix remodeling and tissue engineering

Research paper thumbnail of Enhancement of immunogenicity and neutralizing responses against SARS-CoV-2 spike protein using the Fc fusion fragment

Life Sciences

Vaccination has played an important role in protecting against death and the severity of COVID-19... more Vaccination has played an important role in protecting against death and the severity of COVID-19. The recombinant protein vaccine platform has a long track record of safety and efficacy. Here, we fused the SARS-CoV-2 spike S1 subunit to the Fc region of IgG and investigated immunogenicity, reactivity to human vaccinated sera, and neutralizing activity as a candidate protein vaccine. Materials and method: We evaluated the immunogenicity of CHO-expressed S1-Fc fusion protein and tag-free S1 protein in rabbits via the production of S1-specific polyclonal antibodies. We subsequently compared the neutralizing activities of sera from immunized rabbits and human-vaccinated individuals using a surrogate Virus Neutralization Test (sVNT). Key findings: The results indicate that S1-specific polyclonal antibodies were induced in all groups; however, antibody levels were higher in rabbits immunized with S1-Fc fusion protein than tag-free S1 protein. Moreover, the reactivity of human vaccinated sera against S1-Fc fusion protein was significantly higher than tag-free S1 protein. Lastly, the results of the virus-neutralizing activity revealed that vaccination with S1-Fc fusion protein induced the highest level of neutralizing antibody response against SARS-CoV-2. Significance: Our results demonstrate that the S1 protein accompanied by the Fc fragment significantly enhances the immunogenicity and neutralizing responses against SARS-CoV-2. It is hoped that this platform can be used for human vaccination.

Research paper thumbnail of Mesenchymal Stromal Cells and their EVs as Potential Leads for SARSCoV2 Treatment

Current Stem Cell Research & Therapy

: In December 2019, a betacoronavirus was isolated from pneumonia cases in China and rapidly turn... more : In December 2019, a betacoronavirus was isolated from pneumonia cases in China and rapidly turned into a pandemic of COVID-19. The virus is an enveloped positive-sense ssRNA and causes a severe respiratory syndrome along with a cytokine storm, which is the main cause of most complications. Therefore, treatments that can effectively control the inflammatory reactions are necessary. Mesenchymal Stromal Cells and their EVs are well-known for their immunomodulatory effects, inflammation reduction, and regenerative potentials. These effects are exerted through paracrine secretion of various factors. Their EVs also transport various molecules such as microRNAs to other cells and affect recipient cells' behavior. Scores of research and clinical trials have indicated the therapeutic potential of EVs in various diseases. EVs also seem to be a promising approach for severe COVID-19 treatment. EVs have also been used to develop vaccines since EVs are biocompatible nanoparticles that can be easily isolated and engineered. In this review, we have focused on the use of Mesenchymal Stromal Cells and their EVs for the treatment of COVID-19, their therapeutic capabilities, and vaccine development.

Research paper thumbnail of A novel hybrid polymer of PCL/fish gelatin nanofibrous scaffold improves proliferation and differentiation of Wharton's jelly‐derived mesenchymal cells into islet‐like cells

Artificial Organs

BackgroundUsing a different source of stem cells to compensate for the lost beta cells is a promi... more BackgroundUsing a different source of stem cells to compensate for the lost beta cells is a promising way to cure diabetic patients. Besides, the best efficiency of insulin‐producing cells (IPCs) will appear when we culture them in an environment similar to inside the body. Hence, three‐dimensional (3D) culture ameliorates the differentiation of diverse kinds of stem cells into IPCs compared to those differentiated in two‐dimensional (2D) culture. In this study, we aim to create an ideal differentiation environment by using PCL/Fish gelatin nanofibrous scaffolds to differentiate Wharton's jelly‐derived mesenchymal cells (WJ‐MSCs) to IPCs and compare them with a 2D cultured group.MethodsThe evaluation of cellular, molecular, and functional properties of differentiated cells on the 3D and 2D cultures was investigated by several assays such as electron microscopy, quantitative PCR, immunochemistry, western blotting, and ELISA.ResultsThe in vitro studies showed that WJ‐MSCs differen...

Research paper thumbnail of The use of mesenchymal stem cells in the process of treatment and tissue regeneration after recovery in patients with Covid-19

Gene, 2021

In addition to causing health concerns, the new coronavirus has been considered in the world with... more In addition to causing health concerns, the new coronavirus has been considered in the world with its unknown mechanism of physiopathogenesis and long-term effects after patient recovery. Pulmonary, renal, hepatic and cardiac complications have been reported so far. Beside the researchers' focus on finding vaccines and using conventional therapies, cell-based therapy might be an effective therapeutic strategy. The use of mesenchymal stem cells (MSCs) is one of the options due to their immunomodulatory properties and their proven effects in the treatment of many diseases. As MSCs are not infected with covid-19, there is evidence that it modulates the immune system and prevents the virus from clotting. Despite the beginning of numerous clinical trials in the use of mesenchymal stem cells, it is necessary to set a practical guideline that specifies items such as cell origin, number of cells, frequency of injection, injection site, etc.

Research paper thumbnail of Application of a novel bioreactor for in vivo engineering of pancreas tissue

Journal of cellular physiology, Jan 13, 2017

Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplanta... more Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplantation is an acceptable treatment for native organ failure. However, it is associated with several problems due to a number of reasons, such as the lack of appropriate donors and immunosuppression. In our present study, a novel model is presented for in vivo recellularization of acellular pancreas by implanting between the host pancreas and the adjacent omental flap. In this study, the pancreases were harvested and cannulated via the common bile duct and then, the scaffolds were acellularized by a detergent-based protocol. After that, the abdomens of 35 rats were opened and the spleen was extracted with the adjacent omentum, and placed outside the abdomen. The acellularized scaffold was stretched over the host pancreas and the omentum was wrapped around it to make a sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked with Prolene 4-0 on four sides. All samples...

Research paper thumbnail of Nisin and non-essential amino acids: new perspective in differentiation of neural progenitors from human-induced pluripotent stem cells in vitro

Human cell, 2021

Over the past decades, stem cell therapy has been investigated as a promising approach towards va... more Over the past decades, stem cell therapy has been investigated as a promising approach towards various diseases, including neurodegenerative disorders. Stem cells show the capability to differentiate into neuronal progenitor cells in vitro. In the present study, the differentiation potential of human-induced pluripotent stem cells (hiPSCs) into neural lineages was examined under the efficient induction media containing forskolin and 3-isobutyl-1-methyl-xanthine (IBMX) in the presence of nisin (Ni), non-essential amino acids (NEAA) and combination of those (NEAA-Ni) in vitro. The optimum concentrations of these factors were obtained by MTT assay and acridine orange (AO) staining. The effect of Ni and NEAA on the expression rate of neural-specific markers including NSE, MAP2, and ß-tubulin III was studied via immunocytochemistry (ICC) and real-time RT-PCR analyses. Our results indicated that the induction medium containing Ni or NEAA increased the gene and protein expression of NSE, M...