Publications by authors named "Masoud Soleimani"

521 Publications

Therapeutic role of mesenchymal stem cell-derived exosomes in respiratory disease.

Stem Cell Res Ther 2022 May 12;13(1):194. Epub 2022 May 12.

Applied Cell Science and Hematology Department, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.

Exosomes are extracellular vesicles found in various tissues, blood circulation, and tissue fluids, secreted into the extracellular environment by fusing a multivesicular body with a plasma membrane. Various cell types release these vesicles to contribute to many cellular functions, including intercellular communication, cell proliferation, differentiation, angiogenesis, response to stress, and immune system signaling. These natural nanoparticles have therapeutic effects in various diseases and exhibit a behavior similar to the cell from which they originated. In the meantime, exosomes derived from mesenchymal stem cells have attracted the attention of many researchers and physicians due to their unique ability to modulate the immune system, repair tissue and reduce inflammation. Numerous clinical and preclinical studies have examined the effect of MSC-derived exosomes in various diseases, and their results have been published in prestigious journals. This review article discusses the biogenesis and sources of exosomes, MSC-derived exosomes, the use of these exosomes in regenerative medicine, and treatments based on exosomes derived from stem cells in respiratory diseases.
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http://dx.doi.org/10.1186/s13287-022-02866-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096764PMC
May 2022

Recent developments in miRNA based recombinant protein expression in CHO.

Biotechnol Lett 2022 May 4. Epub 2022 May 4.

Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

It is widely accepted that the growing demand for recombinant therapeutic proteins has led to the expansion of the biopharmaceutical industry and the development of strategies to increase recombinant protein production in mammalian cell lines such as SP2/0 HEK and particularly Chinese hamster ovary cells. For a long time now, most investigations have been focused on increasing host cell productivity using genetic manipulating of cellular processes like cell cycle, apoptosis, cell growth, protein secretory and other pathways. In recent decades MicroRNAs beside different genetic engineering tools (e.g., TALEN, ZFN, and Crisper/Cas) have attracted further attention as a tool in the genetic engineering of host cells to increase protein expression levels. Their ability to simultaneously target multiple mRNAs involved in one or more cellular processes made them a favorable tool in this field. Accordingly, this study aimed to review the methods of selecting target miRNA for cell line engineering, miRNA gain- or loss-of-function strategies, examples of laboratory and pilot studies in this field and discussed advantages and disadvantages of this technology.
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http://dx.doi.org/10.1007/s10529-022-03250-1DOI Listing
May 2022

NETosis and SARS-COV-2 infection related thrombosis: a narrative review.

Thromb J 2022 Mar 30;20(1):13. Epub 2022 Mar 30.

Department of hematology, Tarbiat Modares University, Tehran, Iran.

Background: Coronavirus disease 2019 (COVID-19) infection is related to immune hyperactivity, the release of inflammatory cytokines, and immunothrombosis. Among the underlying mechanisms in COVID-19 thrombosis, neutrophil extracellular traps (NETs) formation, NETosis, may have a significant role. COVID-19 thrombi obtained from extracorporeal membrane oxygenation contained an accumulation of neutrophils and in a higher amount of NETs when compared with non-COVID-19 thrombi specimens.

Main Body: During sepsis and inflammatory status, NETs released from neutrophils and histones and nucleosomes extruded into the extracellular space and take part in the host innate immunity defense, inflammation, and thrombosis. Excessive NETosis is related to clinical progression and respiratory failure in infections and sepsis. NETosis act as a scaffold for thrombus formation, and new associative data support the relation between deregulated immune responses with thrombus formation and organ failure. NETosis is reported in COVID-19 patients. In COVID-19 infection, overproduction of tissue factor (TF) by neutrophils has a role in immunothrombosis. Additionally, NETs can trap TF pathway inhibitor (TFPI) as the only endogenous protein that effectively inhibits the activity of the significant proteases- complexes, TF-FVIIa and prothrombinase.

Conclusion: Because of NETosis can induce intrinsic and extrinsic coagulation cascade activation through the production of TF, activation of FXII, and inhibition of TFPI and fibrinolysis and induce immunothrombosis, targeting NETosis may diminish thrombus formation related to NETs in COVID-19 patients.
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http://dx.doi.org/10.1186/s12959-022-00375-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965217PMC
March 2022

Risk Factors of Graft-Versus-Host Disease in the Iranian Allogeneic Hematopoietic Stem Cell Transplantation: A 10-Year Experience.

Med J Islam Repub Iran 2021 2;35:145. Epub 2021 Nov 2.

Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thus, it is necessary to evaluate the risk factors of GVHD in allo-HSCT. Herein, we studied the effects of some risk factors on GVHD incidence in patients with allo-HSCT. We retrospectively evaluated the GVHD incidences and risk factors in 199 patients diagnosed with hematological disorders who underwent allo-HSCT in Taleghani hospital, Tehran, Iran, between 2007 and 2017. The univariable and multivariable analyses of time to event data were performed using the Logistic regression model. Computations were performed using SAS, and the level of statistical significance for univariable and multivariable analyses was set at 20% and 10%, respectively. Acute GVHD (aGVHD) was seen in 59 (29.6%) patients, and 18 (9%) patients developed chronic GVHD (cGVHD). The odds of GVHD incidence in male to female transplants was 3.49 times greater than the male-to-male transplantations (CI, 1.16, 11.5; p<0.001). The patients with body mass index (BMI) below 18.5 had 96% lower odds of GVHD incidence compared with those with BMI above 30 (CI, 0.007-0.27; p=0.013). The odds of GVHD incidence in patients who were negative for cytomegalovirus (CMV) antigen was 76% lower than patients with positive CMV antigen (CI, 0.06-0.93; p=0.081). In a nutshell, our results indicated that the donor-recipient gender disparity, the recipient's BMI, and CMV infection/reactivation status might be pivotal risk factors, which should be taken into account for prevention and management of GVHD.
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http://dx.doi.org/10.47176/mjiri.35.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840863PMC
November 2021

A composite bilayer scaffold functionalized for osteochondral tissue regeneration in rat animal model.

J Tissue Eng Regen Med 2022 Mar 23. Epub 2022 Mar 23.

Celltech Pharmed Company, Tehran, Iran.

Osteochondral defects are defined most typically by damages to both cartilage and subchondral bone tissue. It is challenging to develop bilayered scaffolds that regenerate both of these lineages simultaneously. In the present study, an electrospun bilayer nanofibrous scaffold was designed to repair osteochondral lesions. A nanocomposite of hydroxyapatite, strontium, and reduced graphene oxide were combined with polycaprolactone polymer to fabricate the osteogenic differentiation layer. Additionally, the chondrogenic differentiation layer was also formed using polyethersulfone polymer and benzyl hyaluronan. The physical, mechanical, and chemical properties of the scaffolds were determined, and adipose-derived mesenchymal stem cells were cultured on each layer to evaluate their biocompatibility and differentiation potential. Cell viability, mineralization, alkaline phosphatase enzyme (ALP) expression, and extracellular calcium deposition were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, alizarin red staining, ALP activity, and calcium deposition. Real-time polymerase chain reaction (PCR) was used to assess the expression levels of osteogenic (Collagen I, Runx II, ALP, Osteocalcin) and chondrogenic (Sox9, Collagen II (Col II), Aggrecan) genes. Finally, the osteochondral scaffold was created by electrospinning these two layers for 2 days. The scaffold was grafted into the osteochondral defect of a Wistar rat's knee. 60 days after surgery, real-time PCR, immunohistochemistry (IHC), and hematoxylin and eosin staining were performed. The expression of chondrogenic and osteogenic genes was increased compared to the control group, as confirmed by real-time PCR. Furthermore, IHC revealed a rise in Col II and Collagen X expression. Finally, in vivo and in vitro studies have shown that the electrospun bilayer scaffold is biocompatible, which facilitates osteochondral healing.
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http://dx.doi.org/10.1002/term.3297DOI Listing
March 2022

Formation of organoid-like structures in the decellularized rat testis.

Iran J Basic Med Sci 2021 Nov;24(11):1523-1528

Department of Hematology and Stem Cell Therapy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Objectives: In testis, the extracellular matrix (ECM) in addition to the supportive role for cells in the seminiferous epithelium, is also essential for the accurate functioning of these cells. Thus, using a decellularized testicular ECM (DTECM), as a scaffold for three-dimensional (3D) culture of testicular cells can mimic native ECM for studying spermatogenesis.

Materials And Methods: The rat testis was decellularized via perfusion of 0.5% sodium dodecyl sulfate (SDS) for 48 hr, followed by 1% Triton X-100 for 6 hr, and then 1% DNase I for 1 hr. The efficiency of decellularization was evaluated by histology, immunohistochemistry (IHC), scanning electron microscopy (SEM), and MTT test. The prepared scaffolds were recellularized with testicular cells and cultured and assessed with hematoxylin-eosin (H&E) staining after two weeks.

Results: Based on the H&E image, no trace of cell components could be observed in DTECM. IHC images demonstrated collagen types I and IV, laminin, and fibronectin were preserved. Masson's trichrome and alcian blue staining revealed that collagen and glycosaminoglycans (GAGs) were retained, and the SEM image indicated that 3D testicular architecture remained after the decellularization process. Based on the results of the MTT test, DTECM was cytocompatible, and H&E images represented that DTECM supports testicular cell arrangements in seminiferous tubule-like structures (STLSs) and organoid-like structures (OLSs).

Conclusion: The results showed that the applied protocol successfully decellularized the testis tissue of the rat. Therefore, these scaffolds may provide an appropriate vehicle for in vitro reconstruction of the seminiferous tubule.
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http://dx.doi.org/10.22038/IJBMS.2021.58294.12948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917852PMC
November 2021

Post-hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors.

Health Sci Rep 2022 Mar 8;5(2):e536. Epub 2022 Mar 8.

Hematopoietic Stem Cell Research Center Shahid Beheshti University of Medical Sciences Tehran Iran.

Background And Aims: Despite the revolutionary effects of hematopoietic stem cell transplantation (HSCT) in treating hematological malignancies, post-HSCT relapse is considered a critical concern of clinicians. Residual malignant cells employ many mechanisms to evade immune surveillance and survive to cause relapse after transplantation. One of the immune-frustrating mechanisms through which malignant cells can compromise the antitumor effects is misusing the self-limiting system of immune response by overexpressing inhibitory molecules to interact with the immune cells, leading them to so-called "exhausted" and ineffective. Introduction of these molecules, known as immune checkpoints, and blocking them was a prodigious step to decrease the relapses.

Methods: Using keywords , , and , we investigated the literature to figure out the role of the immune checkpoints in the HSCT setting. Studies in which these agents were administrated for relapse after transplantation were reviewed. Factors such as the interval from the transplant to relapse, previous treatment history, adverse events, and the patients' outcome were extracted.

Results: Here we provided a mini-review discussing the experiences of three immune checkpoints, including nivolumab, pembrolizumab, and ipilimumab, as well as the pros and cons of using their blockers in relapse control after HSCT. In conclusion, it seems that CI therapy seems effective for this population. Future investigations may provide detailed outlook of this curative options.
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http://dx.doi.org/10.1002/hsr2.536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905133PMC
March 2022

Safety of Intraparenchymal Injection of Allogenic Placenta Mesenchymal Stem Cells Derived Exosome in Patients Undergoing Decompressive Craniectomy Following Malignant Middle Cerebral Artery Infarct, A Pilot Randomized Clinical Trial.

Int J Prev Med 2022 19;13. Epub 2022 Jan 19.

Department of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Malignant middle cerebral artery infarct (mMCAI) largely contributes to high mortality and physical disability among adults. Surviving individuals may not have proper outcomes and suffer from severe lasting disabilities. Utilization of stem cells and paracrine factor for regenerative purposes is considered as a potential strategy for patients with neurological deficits. While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) reduce post-treatment neurological deficits and prevent disability and also promote recovery, few randomized clinical trials (RCT) have assessed exosome therapy in humans.

Methods: In this RCT, we assessed the safety of intraparenchymal injection placenta MSC-derived Exosome in mMCAI patients with average age of 62 years between January, 2019, till September, 2020. The study was done in a single-center as an open-label RCT, with a 3-months follow-up. Primary outcomes assessed the safety and also disability indexes were followed.

Results: Five mMCAI patients were included with mean NIHSS: 17.6 ± 5.02. The mean MRS was 3.25 ± 0.95 in three patients. No serious adverse events were observed. Hematoma or local reaction as excessive edema were not seen at the site of injection.

Conclusions: Intraparenchymal implantation of MSC-EXO showed no post-interventional adverse effects in five ischemic stroke patients. It is proposed Local injection Exosome treatment following mMCAI can be safe and in future, it would be applied as a supportive, restorative and preventive treatment in patients who suffer from acute ischemic stroke and post ischemic disability.
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http://dx.doi.org/10.4103/ijpvm.ijpvm_441_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883670PMC
January 2022

Biodistribution of Cy5-labeled Thiolated and Methylated Chitosan-Carboxymethyl Dextran Nanoparticles in an Animal Model of Retinoblastoma.

J Ophthalmic Vis Res 2022 Jan-Mar;17(1):58-68. Epub 2022 Jan 21.

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: The use of more potent medicine for local chemotherapy of retinoblastoma in order to minimize local and systemic adverse effects is essential. The main goal of this investigation was to assess the biodistribution of thiolated and methylated chitosan-carboxymethyl dextran nanoparticles (CMD-TCs-NPs and CMD-TMC-NPs) following intravitreal (IVT) injection into rat eyes with retinoblastoma.

Methods: An ionic gelation method was used to fabricate Cy5-labelled CMD-TCs-NPs and CMD-TMC-NPs. The NPs were characterized. Cellular internalization of Cy5-labelled NPs was investigated using confocal microscopy and the absorption of labeled NPs was quantified by flow cytometry in human retinoblastoma (Y79) cells. In addition, the Cy5-labeled distribution of nanoparticles in the posterior segment of the eye was histologically imaged by confocal microscopy after IVT injection of NPs into the eyes of rats with retinoblastoma.

Results: CMD-TCs-NPs and CMD-TMC-NPs showed a mean diameter of 34 3.78 nm and 42 4.23 nm and zeta potential of +11 2.27 mV and +29 4.31mV, respectively. The in vivo study of intraocular biodistribution of Cy5-labeled CMD-TCs-NPs and CMD-TMC-NPs revealed that there is more affinity of CMD-TCs-NPs to the retina and retinoblastoma tumor after IVT administration while methylated chitosan nanoparticles are immobilized in the vitreous and are not able to reach the retina even after 24 hr.

Conclusion: The ionic gelation technique was efficient in synthesizing a biocompatible polymeric nanosystem for drug delivery into the posterior segment of the eye. The current study demonstrated increased ocular bioavailability of CMD-TCs-NPs relative to CMD-TMC-NPs in retinoblastoma induced rat eyes.
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http://dx.doi.org/10.18502/jovr.v17i1.10171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8850845PMC
January 2022

The miR-142 Suppresses U-87 Glioblastoma Cell Growth by Targeting EGFR Oncogenic Signaling Pathway.

Iran J Pharm Res 2021 ;20(4):202-212

Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Glioblastoma is the most lethal malignancy of the brain and is resistant to conventional cancer treatments. Gene-therapy approaches like using tumor suppressor miRNAs are promising in the treatment of glioblastoma. They control the expression of oncogenes and influence tumor features and behaviors. Therefore, in the present study, it was predicted that miR-142 regulates oncogenic epidermal growth factor receptor () signaling pathway via TargetScan and miRWalk online tools. Its differential expression level was reduced in glioblastoma according to the previous microarray results, and its predicted target genes were upregulated, as shown by the Expression Atlas. The miR-142 was overexpressed in U-87 glioblastoma cells via lentiviral transduction, and the way it influences proliferation and migration of cells was investigated through MTT assay and wound healing assay. Apoptosis rate was also measured via the Annexin V assay, and cell-cycle analysis was done. Then, real-time polymerase chain reaction (real-time PCR) and western blotting were performed to assess fold changes in mRNA and protein levels of the miR-142 predicted targets. Direct target genes of miR-142 were confirmed through a dual-luciferase reporter assay. The miR-142 significantly suppressed cell proliferation and migration and induced apoptosis and cell-cycle arrest in U-87 glioblastoma cells. This was accompanied by a decrease in expression of SHC adaptor protein 4 (), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (), v-akt murine thymoma viral oncogene homolog 1 (), Kirsten rat sarcoma viral oncogene homolog (), and mitogen-activated protein kinase 8 () oncogenes at mRNA and protein levels in glioblastoma cells. Also, was demonstrated as a direct target of miR-142. Overall, miR-424 acts as tumor suppressor miRNA in glioblastoma cells.
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http://dx.doi.org/10.22037/ijpr.2021.115089.15193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842594PMC
January 2021

Aspirin effect on bone remodeling and skeletal regeneration: Review article.

Tissue Cell 2022 Feb 7;76:101753. Epub 2022 Feb 7.

Department of Tissue engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

Bone tissues are one of the most complex tissues in the body that regenerate and repair themselves spontaneously under the right physiological conditions. Within the limitations of treating bone defects, mimicking tissue engineering through the recruitment of scaffolds, cell sources and growth factors, is strongly recommended. Aspirin is one of the non-steroidal anti-inflammatory drugs (NSAIDs) and has been used in clinical studies for many years due to its anti-coagulant effect. On the other hand, aspirin and other NSAIDs activate cytokines and some mediators in osteoclasts, osteoblasts and their progenitor cells in a defect area, thereby promoting bone regeneration. It also stimulates angiogenesis by increasing migration of endothelial cells and the newly developed vessels are of emergency in bone fracture repair. This review covers the role of aspirin in bone tissue engineering and also, highlights its chemical reactions, mechanisms, dosages, anti-microbial and angiogenesis activities.
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http://dx.doi.org/10.1016/j.tice.2022.101753DOI Listing
February 2022

The potential role of miR-1290 in cancer progression, diagnosis, prognosis, and treatment: An oncomiR or onco-suppressor microRNA?

J Cell Biochem 2022 03 13;123(3):506-531. Epub 2021 Dec 13.

Departamento de Ciencias del Ambiente, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.

Cancer is one of the leading causes of death in humans because of the lack of early diagnosis, distant metastases, and the resistance to adjuvant therapies, including chemotherapy and radiotherapy. In addition to playing an essential role in tumor progression and development, microRNAs (miRNAs) can be used as a robust biomarker in the early detection of cancer. MiR-1290 was discovered for the first time in human embryonic stem cells, and under typical physiological situations, plays an essential role in neuronal differentiation and neural stem cell proliferation. Its coding sequence is located at the 1p36.13 regions in the first intron of the aldehyde dehydrogenase 4 gene member A1. miR-1290 is out of control in many cancers such as breast cancer, colorectal cancer, esophageal squamous cell carcinoma, gastric cancer, lung cancer, pancreatic cancer, and plays a vital role in their development. Therefore, it is suggested that miR-1290 can be considered as a potential diagnostic and therapeutic target in many cancers. In addition to the importance of miR-1290 in the noninvasive diagnosis of various cancers, this systematic review study discussed the role of miR-1290 in altering the expression of different genes involved in cancer development and chemo-radiation resistance. Moreover, it considered the regulatory effect of natural products on miR-1290 expression and the interaction of lncRNAs by miR-1290.
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http://dx.doi.org/10.1002/jcb.30191DOI Listing
March 2022

AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines.

Cell J 2021 Oct 29;23(5):503-509. Epub 2021 Aug 29.

Department of Haematology and Blood Banking, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Objective: Multiple myeloma (MM) is the clonal proliferation of neoplastic plasma cells in the bone marrow. Although bortezomib (BTZ) is a crucial drug for the treatment of MM, drug resistance is a major problem. OncomiR-19a plays an oncogenic role in many cancers, including MM; however, the function of miR-19a in the pathogenesis of MM and drug resistance has not been completely identified. The present research aims to investigate the inhibition of miR-19a by an antagomir to determine BTZ responsiveness, and determine if miR-19a can be a prognostic biomarker for MM.

Materials And Methods: In this experimental study, viability and apoptosis of myeloma cells were analysed by the colorimetric 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) and Annexin V/propidium iodide (PI) flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to evaluate the expression levels of miR-19a, its targets , B-cell lymphoma 2 (), and (antiapoptotic and cell cycle related genes) at the mRNA level.

Results: miR-19a was downregulated and exacerbated in transfected cells treated with BTZ. The rate of apoptosis in the myeloma cells after BTZ treatment considerably increased, which indicated an increase in the mRNA of , and . A decrease in STAT3 was also observed.

Conclusion: OncomiR-19a, as a biomarker, may induce better responsiveness to BTZ in myeloma cell lines through its targets and . In the future, this biomarker may provide new therapeutic targets for MM.
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http://dx.doi.org/10.22074/cellj.2021.7302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588822PMC
October 2021

Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis.

Mol Biol Rep 2022 Jan 24;49(1):19-29. Epub 2021 Nov 24.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: The tumor necrosis factor (TNF)-related apoptosis-inducing ligand, TRAIL, an apoptosis-inducing cytokine, has attracted much attention in the treatment of cancer for its selective toxicity to malignant rather than normal cells. However, the apoptosis-inducing ability of TRAIL is weaker than expected primarily due to cancer cell resistance. As one of the dietary flavonoids, kaempferol, has been shown to be antiproliferative and might have a protective effect against TRAIL resistance, particularly for hematologic malignancies.

Methods And Results: Here, we studied the potential of kaempferol to enhance the TRAIL-induced cytotoxicity and apoptosis in human chronic myelogenous leukemia (CML) cell line K-562, as well as the expression of specific genes with impact on TRAIL signal regulation. Analysis of flowcytometry data showed that treatment with kaempferol did enhance sensitivity of CML cells to pro-apoptotic effects of anti-TRAIL antibody. Although the gene expression levels were heterogeneous, cFLIP, cIAP1 and cIAP2 expression were generally downregulated where co-treatment of kaempferol and TRAIL was employed and these effects appeared to be dose-dependent. We further demonstrated that the expression of death receptors 4 and 5 tended to increase subsequent to the combination treatment.

Conclusions: Consequently, it is reasonable to conclude that sensitization of chronic leukemia cells to TRAIL by kaempferol in vitro should be considered as a way of focusing clinical attention on leukemia therapy.
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http://dx.doi.org/10.1007/s11033-021-06778-zDOI Listing
January 2022

Hypoxia preconditioned mesenchymal stem cell-derived exosomes induce ex vivo expansion of umbilical cord blood hematopoietic stem cells CD133+ by stimulation of Notch signaling pathway.

Biotechnol Prog 2022 01 18;38(1):e3222. Epub 2021 Nov 18.

Department of Hematology and Cell Therapy, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Mesenchymal stem cells (MSCs) are crucial cells that play an essential role in the maintenance, self-renewal, and proliferation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in the bone marrow niche. It has been proven that MSCs can be used as a feeder layer for the proliferation of HSCs to enhance the number of HPCs and HSCs. Recently, it has been demonstrated that MSC-derived exosome (MSC-DE) has critical roles in different biological processes in bone marrow (BM). In the current research, we examined the importance of hypoxia-preconditioned MSC-derived exosomes (HP-MSC-DE) and normoxia-preconditioned MSC-derived exosomes (NP-MSC-DE) in the self-renewal and long-term clonogenic potential of umbilical cord blood hematopoietic stem cells (UCB-HSCs). We showed that the secretion rate and component of the exosome (EXO) were changed in HP-MSC-DE compared to NP-MSC-DE. Notably, the Jagged-1 (Notch ligand) content of EXO was much more plentiful in HP-MSC-DE compared to NP-MSC-DE. The addition of HP-MSC-DE enriched by Jagged-1 to the co-culture system stimulates the Notch pathway on the membrane of UCB-HSCs CD133+ and enhances proliferation. HP-MSC-DE induction using an anti-Jagged-1 antibody suppresses all biological functions of the Jagged-1 protein. Importantly, HP-MSC-DE containing Jagged-1 could change the biology of HSCs CD133+ and increase the self-renewal capacity, quiescence, and clonogenic potential of CD133+ cells. Moreover, they support generating a large number of primitive cells. Our study signified the importance of HP-MSC-DE in the proliferation of UCB-HSCs CD133+, which manifested therapeutic applications of EXO in the enhanced number of HSCs and subsequently alleviated bone marrow transplantation.
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http://dx.doi.org/10.1002/btpr.3222DOI Listing
January 2022

Phosphatidylinositol 3-kinase signaling inhibitors for treatment of multiple myeloma: From small molecules to microRNAs.

J Oncol Pharm Pract 2022 Jan 6;28(1):149-158. Epub 2021 Oct 6.

Hematopoietic Stem Cell Research Center, 556492Shahid Beheshti University of Medical Sciences, Iran.

Multiple myeloma is one of the most hard-to-treat cancers among blood malignancies due to the high rate of drug resistance and relapse. The researchers are trying to find more effective drugs for treatment of the disease. Hence, the use of drugs targeting signaling pathways has become a powerful weapon. Overactivation of phosphatidylinositol 3-kinase signaling pathways is frequently observed in multiple myeloma cancer cells, which increases survival, proliferation, and even drug resistance in such cells. In recent years, drugs that inhibit the mediators involved in this biological pathway have shown promising results in the treatment of multiple myeloma. In the present study, we aimed to introduce phosphatidylinositol 3-kinase signaling inhibitors which include small molecules, herbal compounds, and microRNAs.
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http://dx.doi.org/10.1177/10781552211035369DOI Listing
January 2022

Improvement of Heart Function After Transplantation of Encapsulated Stem Cells Induced with miR-1/Myocd in Myocardial Infarction Model of Rat.

Cell Transplant 2021 Jan-Dec;30:9636897211048786

Department of Cell and Molecular Biology, Faculty of Biological Science and Technology, Isfahan University, Isfahan, Iran.

Cardiovascular disease is one of the most common causes of death worldwide. Mesenchymal stem cells (MSCs) are one of the most common sources in cell-based therapies in heart regeneration. There are several methods to differentiate MSCs into cardiac-like cells, such as gene induction. Moreover, using a three-dimensional (3D) culture, such as hydrogels increases efficiency of differentiation. In the current study, mouse adipose-derived MSCs were co-transduced with lentiviruses containing microRNA-1 () and Myocardin (). Then, expression of cardiac markers, such as NK2 homeobox 5(), GATA binding protein 4 (), and troponin T type 2 () was investigated, at both gene and protein levels in two-dimensional (2D) culture and chitosan/collagen hydrogel (CS/CO) as a 3D culture. Additionally, after induction of myocardial infarction (MI) in rats, a patch containing the encapsulated induced cardiomyocytes (iCM/P) was implanted to MI zone. Subsequently, 30 days after MI induction, echocardiography, immunohistochemistry staining, and histological examination were performed to evaluate cardiac function. The results of quantitative real -time polymerase chain reaction (qRT-PCR) and immunocytochemistry showed that co-induction of and in MSCs followed by 3D culture of transduced cells increased expression of cardiac markers. Besides, results of in vivo study implicated that heart function was improved in MI model of rats in iCM/P-treated group. The results suggested that induction combined with encapsulation of transduced cells in CS/CO hydrogel increased efficiency of MSCs differentiation into iCMs and could improve heart function in MI model of rats after implantation.
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http://dx.doi.org/10.1177/09636897211048786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493326PMC
February 2022

Expansion of cord blood stem cells in fibronectin-coated microfluidic bioreactor.

Hematol Transfus Cell Ther 2021 Sep 10. Epub 2021 Sep 10.

School of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

Background: Hematopoietic stem/progenitor cell transplantation is the main treatment option for hematological malignancies and disorders. One strategy to solve the problem of low stem cell doses used in transplantation is pre-transplant expansion. We hypothesized that using fibronectin-coated microfluidic channels would expand HSPCs and keep self-renewal potential in a three-dimensional environment, compared to the conventional method. We also compared stem cell homing factors expression in microfluidic to conventional cultures.

Materials And Methods: A microfluidic device was created and characterized by scanning electron microscopy. The CD133+ cells were collected from cord blood and purified. They were subsequently cultured in 24-well plates and microfluidic bioreactor systems using the StemSpan serum-free medium. Eventually, we analyzed cell surface expression levels of the CXCR4 molecule and CXCR4 mRNA expression in CD133+ cells cultured in different systems.

Results: The expansion results showed significant improvement in CD133+ cell expansion in the microfluidic system than the conventional method. The median expression of the CXCR4 in the expanded cell was lower in the conventional system than in the microfluidic system. The CXCR4 gene expression up-regulated in the microfluidic system.

Conclusion: Utilizing microfluidic systems to expand desired cells effectively is the next step in cell culture. Comparative gene expression profiling provides a glimpse of the effects of culture microenvironments on the genetic program of HSCs grown in different systems.
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http://dx.doi.org/10.1016/j.htct.2021.06.011DOI Listing
September 2021

Development of an mRNA-LNP Vaccine against SARS-CoV-2: Evaluation of Immune Response in Mouse and Rhesus Macaque.

Vaccines (Basel) 2021 Sep 10;9(9). Epub 2021 Sep 10.

Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1983969411, Iran.

Among the vaccines have been developed thus far against SARS-CoV-2, the mRNA-based ones have demonstrated more promising results regarding both safety and efficacy. Two remarkable features of the mRNA vaccines introduced by the Pfizer/BioNTech and Moderna companies are the use of (N-methyl-pseudouridine-) modified mRNA and the microfluidics-based production of lipid nanoparticles (LNPs) as the carrier. In the present study, except Anti-Reverse Cap Analog (ARCA), no other nucleoside analogs were employed to synthesize Spike-encoding mRNA using the in vitro transcription (IVT) method. Furthermore, LNPs were prepared via the ethanol injection method commonly used for liposome formation as an alternative for microfluidics-based approaches. The produced mRNA-LNP vaccine was evaluated for nanoparticles characteristics, encapsulation and transfection efficiencies, in vitro cytotoxicity as well as stability and storability. The safety of vaccine was assessed in Balb/c mice injected with mRNA-LNPs containing 10 µg of spike-encoding mRNA. Eventually, the vaccine efficacy in inducing an immune response against SARS-CoV-2 was studied in Balb/c and C57BL/6 mice (received either 1 or 10 µg of mRNA) as well as in rhesus macaque monkeys (infused with mRNA-LNPs containing 100 µg of mRNA). The ELISA and virus neutralizing test (VNT) results showed a significant augmentation in the level of neutralizing antibodies against SARS-CoV-2. Moreover, the ELISA assay showed virus-specific IFN-γ secretion in immunized mice as a marker of T1 cell-based immune response, whereas favorably no change in the production of IL-4 was detected.
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http://dx.doi.org/10.3390/vaccines9091007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472963PMC
September 2021

Switch off inflammation in spleen cells with CD40-targeted PLGA nanoparticles containing dimethyl fumarate.

Colloids Surf B Biointerfaces 2021 Dec 1;208:112091. Epub 2021 Sep 1.

Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

The purpose of this study was designing and synthesizing a PLGA formulation targeted with anti-CD40 monoclonal antibody, which has suitable physicochemical properties as a dimethyl fumarate (DMF) drug delivery system having minimal cytotoxicity. Therefore, this research was performed to determine the effect of anti-CD40mAb-DMF-NPs on the expression of IL-1β, IL-6 and TNF-α cytokine genes in mouse splenocytes. The toxicity of different groups, namely free PLGA, free DMF, DMF-containing PLGA, anti-CD40mAb-DMF-NPs, was evaluated by MTT assay. PLGA formulations conjugated with mAbCD40 were loaded with DMF drug that showed little cytotoxic effect against mouse splenocytes. QRT-PCR method was subsequently used to assess the effect of the mentioned groups on the expression of IL-1β, TNF-α and IL-6 genes. After treatment of the cells with DMF alone or with polymer carriers, the expression of IL-1β, IL-6 and TNF-α cytokine genes was significantly reduced. The decrease in expression was markedly higher in the antibody-targeted nanoparticles group relative to other treatment groups. Our results in this area are promising and provide a good basis for further future studies in this regard.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112091DOI Listing
December 2021

Safety and feasibility of autologous olfactory ensheathing cell and bone marrow mesenchymal stem cell co-transplantation in chronic human spinal cord injury: a clinical trial.

Spinal Cord 2022 Jan 9;60(1):63-70. Epub 2021 Sep 9.

Department of Cell Therapy and Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Study Design: This is a phase I clinical trial.

Objectives: Our objective was to assess the safety and feasibility of autologous mucosal olfactory ensheathing cell (OEC) and bone marrow mesenchymal stem cell (MSC) co-transplantation in people with chronic, complete (American Spinal Injury Association (ASIA) Impairment Scale (AIS) classification A) spinal cord injury (SCI).

Setting: This study was performed at Shohada Tajrish Hospital, Tehran, Iran.

Methods: Three individuals with the traumatic SCI of the thoracic level were enrolled. They received the autologous OEC and MSC combination through the lumbar puncture. All adverse events and possible functional outcomes were documented performing pre- and post-operative general clinical examination, magnetic resonance imaging (MRI), neurological assessment based on the International Standard of Neurological Classification for SCI, and functional evaluation using Spinal Cord Independence Measure version III (SCIM III).

Results: No serious safety issue was recorded during the 2 years of follow-up. MRI findings remained unchanged with no neoplastic tissue formation. AIS improved from A to B in one of the participants. SCIM III evaluation also showed some degrees of progress in this participant's functional ability. The two other research participants had negligible or no improvement in their sensory scores without any changes in the AIS and SCIM III scores. No motor recovery was observed in any of the participants.

Conclusions: Overall, this 2-year trial was not associated with any adverse findings, which may suggest the safety of autologous OEC and bone marrow MSC combination for the treatment of human SCI.
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http://dx.doi.org/10.1038/s41393-021-00687-5DOI Listing
January 2022

The interplay between extracellular matrix and progenitor/stem cells during wound healing: Opportunities and future directions.

Acta Histochem 2021 Oct 6;123(7):151785. Epub 2021 Sep 6.

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

Skin wound healing, a dynamic physiological process, progresses through coordinated overlapping phases to restore skin integrity. In some pathological conditions such as diabetes, wounds become chronic and hard-to-heal resulting in substantial morbidity and healthcare costs. Despite much advancement in understanding mechanisms of wound healing, chronic and intractable wounds are still a considerable challenge to nations' health care systems. Extracellular matrix (ECM) components play pivotal roles in all phases of wound healing. Therefore, a better understanding of their roles during wound healing can help improve wound care approaches. The ECM provides a 3D structure and forms the stem cell niche to support stem cell adhesion and survival and to regulate stem cell behavior and fate. Also, this dynamic structure reserves growth factors, regulates their bioavailability and provides biological signals. In various diseases, the composition and stiffness of the ECM is altered, which as a result, disrupts bidirectional cell-ECM interactions and tissue regeneration. Hence, due to the impact of ECM changes on stem cell fate during wound healing and the possibility of exploring new strategies to treat chronic wounds through manipulation of these interactions, in this review, we will discuss the importance/impact of ECM in the regulation of stem cell function and behavior to find ideal wound repair and regeneration strategies. We will also shed light on the necessity of using ECM in future wound therapy and highlight the potential roles of various biomimetic and ECM-based scaffolds as functional ECM preparations to mimic the native stem cell niche.
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http://dx.doi.org/10.1016/j.acthis.2021.151785DOI Listing
October 2021

A systematic review of extracellular vesicles as non-invasive biomarkers in glioma diagnosis, prognosis, and treatment response monitoring.

Mol Biol Rep 2021 Oct 30;48(10):6971-6985. Epub 2021 Aug 30.

Neurosciences Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

The present systematic review was done to investigate the possible application of Extracellular vesicles (EVs) in the diagnosis, prognosis, and treatment response monitoring of gliomas using available literature to wrap up the final applicable conclusion in this regard. we searched PubMed/MEDLINE, Scopus, and ISI Web of Science databases. Authors evaluated the quality of the included studies by the QUADAS-2 tool. In total, 2037 published datasets were retrieved through systematic search. Upon screening for eligibility, 35 datasets were determined as eligible. Exosome was the EV-subtype described in the majority of studies, and most datasets used serum as the primary EVs isolation source. EVs isolation was primarily conducted by ultracentrifugation. 31 datasets reported that EVs hold considerable potential for being used in diagnostics, with the majority reporting different types of miRNAs as biomarkers. Besides, 8 datasets reported that EVs could be a potential source of prognostic biomarkers. And finally, 3 datasets reported that EVs might be a reliable strategy for monitoring therapy response in glioma patients. According to the findings of the current systematic review, it seems that miR-301, miR-21, and HOTAIR had the highest diagnostic accuracy. However, heterogeneous and limited evidence regarding prognosis and treatment response monitoring precludes us from drawing a practical conclusion regarding EVs.
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http://dx.doi.org/10.1007/s11033-021-06687-1DOI Listing
October 2021

Combining cell therapy with human autologous Schwann cell and bone marrow-derived mesenchymal stem cell in patients with subacute complete spinal cord injury: safety considerations and possible outcomes.

Stem Cell Res Ther 2021 08 9;12(1):445. Epub 2021 Aug 9.

Department of Hematology, Tarbiat Modares University, Tehran, Iran.

Background: Cellular transplantations have promising effects on treating spinal cord injury (SCI) patients. Mesenchymal stem cells (MSCs) and Schwann cells (SCs), which have safety alongside their complementary characteristics, are suggested to be the two of the best candidates in SCI treatment. In this study, we assessed the safety and possible outcomes of intrathecal co-transplantation of autologous bone marrow MSC and SC in patients with subacute traumatic complete SCI.

Methods: Eleven patients with complete SCI (American Spinal Injury Association Impairment Scale (AIS); grade A) were enrolled in this study during the subacute period of injury. The patients received an intrathecal autologous combination of MSC and SC and were followed up for 12 months. We assessed the neurological changes by the American Spinal Injury Association's (ASIA) sensory-motor scale, functional recovery by spinal cord independence measure (SCIM-III), and subjective changes along with adverse events (AE) with our checklist. Furthermore, electromyography (EMG), nerve conduction velocity (NCV), magnetic resonance imaging (MRI), and urodynamic study (UDS) were conducted for all the patients at the baseline, 6 months, and 1 year after the intervention.

Results: Light touch AIS score alterations were approximately the same as the pinprick changes (11.6 ± 13.1 and 12 ± 13, respectively) in 50% of the cervical and 63% of the lumbar-thoracic patients, and both were more than the motor score alterations (9.5 ± 3.3 in 75% of the cervical and 14% of the lumbar-thoracic patients). SCIM III total scores (21.2 ± 13.3) and all its sub-scores ("respiration and sphincter management" (15 ± 9.9), "mobility" (9.5 ± 13.3), and "self-care" (6 ± 1.4)) had statistically significant changes after cell injection. Our findings support that the most remarkable positive, subjective improvements were in trunk movement, equilibrium in standing/sitting position, the sensation of the bladder and rectal filling, and the ability of voluntary voiding. Our safety evaluation revealed no systemic complications, and radiological images showed no neoplastic overgrowth, syringomyelia, or pseudo-meningocele.

Conclusion: The present study showed that autologous SC and bone marrow-derived MSC transplantation at the subacute stage of SCI could reveal statistically significant improvement in sensory and neurological functions among the patients. It appears that using this combination of cells is safe and effective for clinical application to spinal cord regeneration during the subacute period.
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http://dx.doi.org/10.1186/s13287-021-02515-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351425PMC
August 2021

miR-424 induces apoptosis in glioblastoma cells and targets AKT1 and RAF1 oncogenes from the ERBB signaling pathway.

Eur J Pharmacol 2021 Sep 18;906:174273. Epub 2021 Jun 18.

Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address:

Glioblastoma is a lethal and incurable cancer. Tumor suppressor miRNAs are promising gene therapy tools for cancer treatment. In silico, we predicted miR-424 as a tumor suppressor. It had several target genes from the epidermal growth factor receptor (ERBB) signaling pathway that are overactive in most glioblastoma cases. We overexpressed miR-424 by lentiviral transduction of U-251 and U-87 glioblastoma cells confirmed with fluorescent microscopy and real-time quantitative PCR (qRT-PCR). Then the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) proliferation assay and scratch wound migration assay were performed to investigate the miR-424 tumor suppressor effect in glioblastoma. miR-424's effect on glioblastoma apoptosis and cell-cycle arrest was verified using Annexin V- phosphatidylethanolamine (PE) and 7-minoactinomycin D (7-AAD) apoptosis assay and cell-cycle assay. miR-424 predicted target genes mRNA and protein level were measured after miR-424 overexpression in comparison to the control group by qRT-PCR and western blotting, respectively. We confirmed miR-424 direct target genes by dual-luciferase reporter assay. miR-424 overexpression significantly suppressed cell proliferation and migration rate in glioblastoma cells based on the MTT and scratch assays. Flow cytometry results confirmed that miR-424 promotes apoptosis and cell-cycle arrest in glioblastoma cells. Predicted target genes of miR-424 from the ERBB pathway were downregulated by miR-424 overexpression. qRT-PCR and western blotting showed that KRAS, RAF1, MAP2K1, EGFR, PDGFRA, AKT1, and mTOR mRNA expression levels and KRAS, RAF1, MAP2K1, EGFR, and AKT1 protein level, respectively, had significantly decreased as a result of miR-424 overexpression in comparison to the control group. Dual-luciferase reporter assay confirmed that miR-424 directly targets RAF1 and AKT1 oncogenes. Overall, miR-424 acts as tumor suppressor miRNA in glioblastoma cells.
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http://dx.doi.org/10.1016/j.ejphar.2021.174273DOI Listing
September 2021

Cartilage tissue engineering by co-transplantation of chondrocyte extracellular vesicles and mesenchymal stem cells, entrapped in chitosan-hyaluronic acid hydrogel.

Biomed Mater 2021 07 13;16(5). Epub 2021 Jul 13.

Department of Cell Therapy and Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Mesenchymal stem cells (MSCs) on injectable hydrogels are mostly used to regenerate articular cartilage, which would have a variety of outcomes. Chondrocyte extracellular vesicles (EVs) have attracted many attentions for their chondrogenic differentiation capacity; however, the roles of EVs in both chondrogenic differentiation of MSCs and cartilage regeneration are poorly understood yet. In the current study, to investigate the differentiation effects of human articular chondrocyte EVs on adipose-derived MSCs, they were cultured in injectable chitosan-hyaluronic acid (CS-HA) hydrogel and then treated with chondrocyte EVs for 21 days. The continuous treatment of EVs performed on MSCs increased chondrogenic genes' expressions ofandand induced expression of Col II protein. In addition, glycosaminoglycans secretion was detected in the EV-treated MSCs after about 14 days. The therapeutic efficiency of this hydrogel and EVs was studied in a rabbit osteochondral defect model. MRI results revealed that the cartilage regeneration capacity of EV-treated MSCs with CS-HA hydrogel was greater than the untreated MSCs or the EV-treated MSCs without hydrogel. Moreover, histological results showed hyaline-like cartilage in the CS-HA/MSC and CS-HA/EV/MSC groups in the cartilage defect sites. These findings suggested that the chondrocyte-EVs and CS-HA hydrogel could provide the preferable niche for chondrogenic differentiation of MSCs and cartilage regeneration in osteoarthritis cartilage injuries.
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http://dx.doi.org/10.1088/1748-605X/ac0cbfDOI Listing
July 2021

A Bilayered, Electrospun Poly(Glycerol-Sebacate)/Polyurethane-Polyurethane Scaffold for Engineering of Endothelial Basement Membrane.

ASAIO J 2022 01;68(1):123-132

From the Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

In the cardiovascular system, heart valves and vessels are subjected to continuous cyclic mechanical loadings due to the pulsatile nature of blood flow. Hence, in leveraging tissue engineering (TE) strategies to regenerate such a system, the candidate scaffold should not only be biocompatible with the desired biodegradation rate, but it should also be mechanically competent to provide a supportive structure for facilitating stem cells retention, growth, and differentiation. To this end, herein, we introduced a novel scaffold composed of poly(glycerol-sebacate) (PGS) and polyurethane (PU), which comprises of two layers: an electrospun pure PU layer beneath another electrospun PGS/PU layer with a different ratio of PGS to PU (3:2, 1:1, 2:3 Wt:Wt). The electrospun PGS/PU-PU scaffold was mechanically competent and showed intended hydrophilicity and a good biodegradation rate. Moreover, the PGS/PU-PU scaffold indicated cell viability and proliferation within ten days of in vitro cell culture and upon 7 day vascular endothelial growth factor (VEGF) stimulation, supported endothelial differentiation of mesenchymal stem cells by significant overexpression of platelet-endothelial cell adhesion molecule-1, von Willebrand factor, and VEGF receptor 2. The results of this study could be implemented in cardiovascular TE strategies when regeneration of blood vessel or heart valve is desired.
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http://dx.doi.org/10.1097/MAT.0000000000001423DOI Listing
January 2022

Application of iPSCs derived pancreatic β-like cells using pancreatic bio-scaffold.

Exp Cell Res 2021 08 6;405(2):112667. Epub 2021 Jun 6.

Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

This study aimed toengineer a pancreatic tissue. Intact rat pancreases were successfully decellularized, and were reseeded with human-induced pluripotent stem cells using different 2D and 3D culture growth factors. The differentiation process was assessed for the presence of a pancreas-like tissue. The histology and SEM analysis revealed cell attachment in all samples, except for the Exp4, and the Flow-cytometry provided 87% viability for the differentiated cells. In Exp1, PDX1 with the positive expression of 2.87±0.06 was dramatically higher than Exp2 with a 2.44±0.06 reaction. NGN3-reactions were 8±0.1 and 6.6±0.2 in Exp1 and Exp2 at P < 0.05, respectively. C-peptide with the expression of 7.5±0.7 in Exp3 was almost equal to that in Exp1 and Exp2. Glucagon (5.1±1) and PDX1 (3.2±0.82) in Exp3 indicated no significant difference. The significant upregulations of pancreatic endocrine markers (PDX1 and NGN3), and the cell-specific glucose transporter (GLUT2) were observed in the differentiated IPCs in the 3D culture of Exp2 after 21 days. The highest insulin and C-peptide concentrations were observed in Exp2. In Exp3, insulin secretion in response to high glucose and 10 mM arginine was 42.43 ±6.34 μU/ml. A decellularized pancreas in the presence of hiPSCs and growth factors could be efficiently used as a natural scaffold.
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http://dx.doi.org/10.1016/j.yexcr.2021.112667DOI Listing
August 2021

Mesenchymal stem cells loaded with oncolytic reovirus enhances antitumor activity in mice models of colorectal cancer.

Biochem Pharmacol 2021 08 4;190:114644. Epub 2021 Jun 4.

Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran.

Oncolytic viruses (OVs) are promising alternative biological agents for treating cancer. However, triggered immune responses against viruses and their delivery to tumor sites are their primary limitations in cancer therapy. To address these challenges, mesenchymal stem cells (MSCs) can serve as permissive tools for OVs loading and delivery to tumor sites. Here, we evaluated the in vitro and in vivo antitumor capability of adipose-derived mesenchymal stem cells (AD-MSCs) as a new vehicle for Dearing strain of reovirus (ReoT3D) loading. We first isolated and confirmed the purity of MSCs, and the optimized dose of ReoT3D for MSCs loading was computed by a standard assay. Next, we used murine CT26 cell line to establish the colorectal cancer model in BALB/c mice and demonstrated the antitumor effects of MSCs loaded with reovirus. Our results demonstrated that multiplicity of infection (MOI) 1 pfu/cells of reovirus was the safe dose for loading into purified MSCs. Moreover, our anticancer experiments exhibited that treatment with MSCs loaded with ReoT3D was more effective than ReoT3D and MSCs alone. Higher anticancer impact of MSCs loaded with OV was associated with induction of apoptosis, cell cycle arrests, P53 expression in tumor sections, and reduced tumor growth and size. The present results suggest that MSCs as a permissive shuttle for oncolytic virus (OV) delivery increased the anticancer activity of ReoT3D in mice models of colorectal cancer and these findings should be supported by more preclinical and clinical studies.
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http://dx.doi.org/10.1016/j.bcp.2021.114644DOI Listing
August 2021

Gold nanoparticles show potential in vitro antiviral and anticancer activity.

Life Sci 2021 Nov 26;284:119652. Epub 2021 May 26.

Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Aims: Gold nanoparticles (AuNPs) have been attracted interests in the various areas of clinical therapeutics. In this study, we investigated the anticancer and antiviral potential activity of AuNPs against influenza A virus and human glioblastoma (GMB) U-87 and U-251 cell lines.

Main Methods: Gold nanoparticles (AuNPs) were synthesized by citrate reduction method. Then, ultraviolet-visible spectrophotometry (UV-vis spectra) and electron microscopy analysis confirmed the type, size (mean diameter of 17 nm) and distribution of the particles. The AuNPs in vitro antiviral and anticancer effects was evaluated by hemagglutination inhibition (HAI), tissue culture infectious dose 50 (TCID), real-time PCR, MTT, flow cytometry, and scratch assays.

Key Findings: The AuNPs were synthesized in spherical with a mean diameter of 17 ± 2 nm and an absorbance peak at 520 nm. The AuNPs were well tolerable by MDCK cells at concentrations up to 0.5μg/ml and they significantly inhibited the hemagglutination and virus infectivity, particularly when added pre- or during virus infection. Furthermore, anticancer results indicated that AuNPs treatment caused the marked induction of apoptosis and reduced growth and migration capability of U-87 and U-251 cell lines in a time-dependent manner.

Significance: The present results suggest that AuNPs provide promising antiviral and anticancer approaches. Further research is needed to fully elucidate the mode of antiviral and anticancer action of AuNPs against influenza virus infection and human glioblastoma cell lines.
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http://dx.doi.org/10.1016/j.lfs.2021.119652DOI Listing
November 2021
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