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Rasti, M. ,
Piri ardekani, H. ,
Mirhendi, H. ,
Mofidi, M. ,
Dehghani, L. ,
Azimian, V. Journal of Cosmetic Dermatology (14732165) 24(4)
Background: Lipofilling is a natural, low-risk, and long-lasting method for filling, reconstructing, and improving soft tissues such as the face, with minimal discomfort for patients. Many plastic surgeons prefer autologous fat grafting in aesthetic surgery due to its availability, cost-effectiveness, biocompatibility, and absence of allergic and carcinogenic concerns. Despite the advantages of autologous fat injection, one of the main drawbacks is the variable persistence of injected fat tissue. Given the significant implications of this issue in advanced countries, this study aims to investigate the survival of fat cells after freezing at different time intervals (1, 3, and 6 months). Methods: Thirty female participants were enlisted for this research, and the viability of fat cell specimens was assessed at intervals of 0, 1, 3, and 6 months post-freezing at −18°C. The evaluation of viable adipocytes was conducted using the XTT assay, a live/dead staining method using fluorescence microscopy after staining with fluorescein diacetate (FDA) and propidium iodide (PI), along with histological analysis of fat tissue after freezing at the indicated time intervals. Results: The results showed that the viability of frozen fat samples decreases by 34%, 60%, and 80% after 1, 3, and 6 months, respectively, compared to non-frozen samples on Day 0. Conclusions: The findings of this study underscore a rapid decline in adipocyte viability after storage at −18°C at different time intervals (1, 3, and 6 months), at which points only around 60%, 40%, and 20% of fat cells remained viable, respectively. These results suggest that current fat preservation techniques utilizing either a −18°C freezer are not sufficient for maintaining the long-term viability of adipocytes, and alternative cryopreservation methods are needed to preserve fat cells. © 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.
Mozaffari, S. ,
Morovati, H. ,
Gharibi, S. ,
Azimian, V. ,
Mohammadi, R. Current Medical Mycology (24233420) 10
Background and Purpose: Various attempts have been made to find potent and effective alternatives with natural origin and fewer side effects for the current antifungals. This study aimed to determine the antifungal effects of the Hydroalcoholic Extract (HE) and Lyophilized Extract (LE) of Prunus amygdalus hulls on clinical isolates of Candida albicans. Moreover, their effects were compared with fluconazole. Materials and Methods: Following the preparation of botanical compounds, the toxicity, cell viability, and high-performance liquid chromatography (HPLC) of phenolic compounds analyses were assayed. The broth microdilution method was applied to determine the minimum inhibitory concentration (MIC) values of fluconazole, LEs, and HEs against clinical isolates of C. albicans. Results: According to the HPLC results, the HEs and LEs comprised the main nine components, of which chlorogenic and tannic acids were the most abundant ones. Results of the toxicity assays revealed that no dilution of the extract was toxic to the cells, and the percentage of cell viability was similar to that of the control and above 90% in all dilutions. All isolates showed susceptibility to fluconazole (MIC range: 0.12-1 μg/mL). The MIC geometric mean values of C. albicans isolates were 0.29, 11.47, and 48.50 μg/mL for fluconazole, LE, and HE, respectively. Conclusion: Due to their insignificant side effects and cost-effectiveness, these extracts can be introduced as effective antifungals. Further in vivo studies and clinical trials should support the study results. Copyright© 2024, Published by Mazandaran University of Medical Sciences on behalf of Iranian Society of Medical Mycology and Invasive Fungi Research Center.
Rasti, M. ,
Parniaei, A.H. ,
Dehghani, L. ,
Nasr esfahani, S. ,
Mirhendi, H. ,
Yazdani, V. ,
Azimian, V. Regenerative Therapy (23523204) 26pp. 281-289
Introduction: The skin plays a crucial role as a protective barrier against external factors, but disruptions to its integrity can lead to wound formation and hinder the natural healing process. Scar formation and delayed wound healing present significant challenges in skin injury treatment. While alternative approaches such as skin substitutes and tissue engineering exist, they are often limited in accessibility and cost. Exosomes have emerged as a potential solution for wound healing due to their regenerative properties. Methods: In this study, exosomes were isolated from human blood serum using a kit. The exosomes were characterized, and their effects on cell migration were assessed in vitro. Additionally, the wound healing capacity of exosomes was evaluated in vivo using a rat full-thickness wound model. Results: Our in vitro findings revealed that exosomes significantly promoted cell migration. In vivo experiments demonstrated that the injection of exosomes at different areas of the wound accelerated the wound healing process, resulting in wound closure, collagen synthesis, vessel formation, and angiogenesis in the wound area. These results suggest that exosomes have a promising therapeutic potential for expediting wound healing and minimizing scar formation. Conclusions: The findings of this study highlight the potential of exosomes as a novel approach for enhancing wound healing. Exosomes showed positive effects on both cell migration and wound closure in in vitro and in vivo studies, suggesting their potential use as a regenerative therapy for skin injuries. Further research is needed to fully understand the mechanisms underlying the beneficial effects of exosomes on wound healing and to optimize their application in clinical settings. © 2024 The Author(s)
Toghiani, R. ,
Azimian, V. ,
Najafi, H. ,
Mirian, M. ,
Azarpira, N. ,
Abolmaali, S.S. ,
Varshosaz, J. ,
Tamaddon, A.M. Stem Cell Research and Therapy (17576512) 15(1)
Background: Recent advancements in mesenchymal stem cell (MSC) technology have paved the way for innovative treatment options for various diseases. These stem cells play a crucial role in tissue regeneration and repair, releasing local anti-inflammatory and healing signals. However, challenges such as homing issues and tumorigenicity have led to exploring MSC-exosomes as a promising alternative. MSC-exosomes have shown therapeutic potential in conditions like renal ischemia-reperfusion injury, but low production yields hinder their clinical use. Methods: To address this limitation, we examined hypoxic preconditioning of Wharton jelly-derived MSCs (WJ-MSCs) 3D-cultured in spheroids on isolated exosome yields and miR-21 expression. We then evaluated their capacity to load miR-210 into HEK-293 cells and mitigate ROS production, consequently enhancing their survival and migration under hypoxia-reoxygenation conditions. Results: MiR-210 overexpression was significantly induced by optimized culture and preconditioning conditions, which also improved the production yield of exosomes from grown MSCs. The exosomes enriched with miR-210 demonstrated a protective effect by improving survival, reducing apoptosis and ROS accumulation in damaged renal cells, and ultimately promoting cell migration. Conclusion: The present study underscores the possibility of employing advanced techniques to maximize the therapeutic attributes of exosomes produced from WJ-MSC spheroid for improved recovery outcomes in ischemia-reperfusion injuries. © The Author(s) 2024.
Soleiman-dehkordi, E. ,
Reisi-vanani, V. ,
Hosseini, S. ,
Lorigooini, Z. ,
Azimian, V. ,
Farzan, M. ,
Khorasgani, E.M. ,
Lozano, K. ,
Abolhassanzadeh, Z. International Journal of Biological Macromolecules (01418130) 262
Wound infection is still an important challenge in healing of different types of skin injuries. This highlights the need for new and improved antibacterial agents with novel and different mechanisms of action. In this study, by electrospinning process Tanacetum polycephalum essential oil (EO), as a natural antibacterial and anti-inflammatory agent, along with Amoxicillin (AMX) as an antibiotic are incorporated into PVA/gelatin-based nanofiber mats individually and in combination to fabricate a novel wound dressing. Briefly, we fabricated PVA/gelatin loaded by Amoxicillin as first layer for direct contact with wound surface to protects the wound from exogenous bacteria, and then built a PVA/gelatin/Tanacetum polycephalum essential oil layer on the first layer to help cleanses the wound from infection and accelerates wound closure. Finally, PVA/gelatin layer as third layer fabricated on middle layer to guarantee desirable mechanical properties. For each layer, the electrospinning parameters were adjusted to form bead-free fibers. The morphology of fabricated nanofiber scaffolds was characterized by Fourier-transform infrared (FTIR) and scanning electron microscopy (SEM). Microscopic images demonstrated the smooth bead-free microstructures fabrication of every layer of nanofiber with a uniform fiber size of 126.888 to 136.833 nm. While, EO and AMX increased the diameter of nanofibers but there was no change in physical structure of nanofiber. The water contact angle test demonstrated hydrophilicity of nanofibers with 47.35°. Although EO and AMX had little effect on reducing hydrophilicity but nanofibers with contact angle between 51.4° until 65.4° are still hydrophilic. Multilayer nanofibers loaded by EO and AMX killed 99.99 % of both gram-negative and gram-positive bacteria in comparison with control and PVA/gelatin nanofiber. Also, in addition to confirming the non-toxicity of nanofibers, MTT results also showed the acceleration of cell proliferation. In vivo wound evaluation in mouse models showed that designed nanofibrous scaffolds could be an appropriate option for wound treatment due to their positive effect on angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound closure. © 2024
Mahvash, S. ,
Azimian, V. ,
Taymouri, S. ,
Mirian, M. ,
Ramezani-aliakbari, M. ,
Dousti, F. ,
Rostami, M. Journal of Drug Delivery Science and Technology (17732247) 87
Novel biocompatible nanocomposites (NCs) of Anderson-type manganese polyoxomolybdate (MnMo6) in chitosan imidazolium platform (MnMo6@CSIm NCs) were introduced for modulating cytotoxicity profile. The anticancer activity of optimized NCs was evaluated against breast cancer cell lines (MCF-7 & MDA-MB-231) and HUVEC normal cells using the MTT assay. Cellular uptake, apoptosis ratio, and cell migration inhibition were also evaluated on the MDA-MB-231 cell line. The optimized pH-responsive NCs had better anticancer activity than free MnMo6 without cytotoxicity against normal HUVEC cells. The cellular uptake was about 100%, and the apoptosis value was higher (81%) than free MnMo6. Interestingly, the MnMo6@CSIm NCs inhibited the cell migration 1.5 times better than the free MnMo6. These results are fascinating to follow more pre-clinical studies. © 2023 Elsevier B.V.
Shirvanian, M. ,
Azimian, V. ,
Zamanzadeh, Z. ,
Janghorban, M. ,
Mohammadi, E. ,
Ahangarzadeh, S. Advanced Biomedical Research (22779175) 12(1)pp. 242-242
Background: Breast milk is always the best choice for infant's nutrition due to its useful compounds such as immune cells and molecules, oligosaccharides, as well as bacteria and their metabolites. We identified and characterized the isolated strain from human breast milk in this study. Materials and Methods: A total of 20 lactating mothers aged 25 to 34 years were enrolled in our study. We collected the breast milk samples in sterile microtubes. 100 μl of each sample was spread on de Man-Rogosa-Sharpe (MRS) agar plates and incubated aerobically at 37°C for 48 hr. After identifying the isolated strain, initial tests (hemolysis inactivity and L-arginine hydrolysis, catalase), the acid tolerance, bile tolerance, and antibiotics susceptibility of the isolated strain were estimated. Furthermore, the antiproliferative and proapoptotic activities of heat-killed cells) HKC) and cell-free supernatant (CFS) of the strain on the HT-29 cell line were evaluated using MTT assay and flow cytometry analysis, respectively. Results: The isolated strain was Gram-positive, bacilli in shape, catalase-negative, non-hemolytic, and negative for L-arginine hydrolysis. By 16S rRNA gene sequencing, the isolated strain was Lactobacillus fermentum. According to MTT assay and flow cytometry results, the HKC and CFS of the isolated strain reduced the viability of the HT-29 cells. The total apoptosis induced in HT-29 cells by HKC and CFS was 65.98% and 70.1%, respectively. Conclusion: Our findings suggest that this strain, despite the properties of probiotic bacteria, has potential antiproliferative and proapoptotic capabilities. © 2023 Wolters Kluwer Medknow Publications. All rights reserved.
Azimian, V. ,
Gharibi, S. ,
Hosseini rizi, M. ,
Nekookar, A. ,
Mirhendi, H. ,
Rahimmalek, M. ,
Szumny, A. Cells (20734409) 12(23)
Overcoming drug resistance and specifically targeting cancer stem cells (CSCs) are critical challenges in improving cancer therapy. Nowadays, the use of novel and native medicinal plants can provide new sources for further investigations for this purpose. The aim of this study was to assess the potential of S. bachtiarica, an endemic plant with diverse medicinal applications, in suppressing and targeting cancer and cancer stem cells in glioblastoma and breast cancer. The effect of S. bachtiarica on viability, migration, invasion, and clonogenic potential of MDAMB-231 and U87-MG cells was assessed in both two- and three-dimensional cell culture models. Additionally, we evaluated its effects on the self-renewal capacity of mammospheres. The experimental outcomes indicated that S. bachtiarica decreased the viability and growth rate of cells and spheroids by inducing apoptosis and inhibited colony formation, migration, and invasion of cells and spheroids. Additionally, colony and sphere-forming ability, as well as the expression of genes associated with EMT and stemness were reduced in mammospheres treated with S. bachtiarica. In conclusion, this study provided valuable insights into the anti-cancer effects of S. bachtiarica, particularly in relation to breast CSCs. Therefore, S. bachtiarica may be a potential adjuvant for the treatment of cancer. © 2023 by the authors.
Naghi-ganji, N. ,
Saghaei, L. ,
Tavakoli, F. ,
Azimian, V. ,
Mirian, M. ,
Sirous, H. ,
Rostami, M. Research In Pharmaceutical Sciences (17355362) 17(5)pp. 572-584
Background and purpose: Histone deacetylation is one of the essential cellular pathways in the growth and spread of cancer, so the design of histone deacetylase (HDAC) inhibitors as anticancer agents is of great importance in pharmaceutical chemistry. Here, a series of indole acylhydrazone derivatives of 4-pyridone have been introduced as potential histone deacetylase inhibitors. Experimental approach: Seven indole-acylhydrazone-pyridinone derivatives were synthesized via simple, straightforward chemical procedures. The molecular docking studies were accomplished on HDAC2 compared to panobinostat. The cytotoxicity of all derivatives was studied on MCF-7 and MDA-MB-231 breast cancer cell lines by MTT assay. Findings / Results: Molecular docking studies supported excellent fitting to the HADC2 active site with binding energies in the range of -10 Kcal/mol for all derivatives. All compounds were tested for their cytotoxicity against MCF-7 and MDA-MB-231 cell lines; derivatives A, B, F, and G were the best candidates. The half-maximal inhibitory concentration (IC 50) values on MCF-7 were below 25 mg/mL and much lower than those obtained on the MDA-MB-231 cell line. Conclusion and implications: The derivatives showed selectivity toward the MCF-7 cell line, probably due to the higher HDAC expression in the MCF-7 cell line. In this regard, debenzylated derivatives F and G showed slightly better cytotoxicity, which should be more studied in the future. Derivatives A, B, F, and G were promising for future enzymatic studies. © 2022 Wolters Kluwer Medknow Publications. All rights reserved.
Azimian, V. ,
Rafiee l., L. ,
Sheikholeslam, M. ,
Shariati, L. ,
Vaseghi, G. ,
Savoji, H. ,
Javanmard, S.H. ACS Biomaterials Science and Engineering (23739878) 8(11)pp. 4648-4672
Common models used in breast cancer studies, including two-dimensional (2D) cultures and animal models, do not precisely model all aspects of breast tumors. These models do not well simulate the cell-cell and cell-stromal interactions required for normal tumor growth in the body and lake tumor like microenvironment. Three-dimensional (3D) cell culture models are novel approaches to studying breast cancer. They do not have the restrictions of these conventional models and are able to recapitulate the structural architecture, complexity, and specific function of breast tumors and provide similar in vivo responses to therapeutic regimens. These models can be a link between former traditional 2D culture and in vivo models and are necessary for further studies in cancer. This review attempts to summarize the most common 3D in vitro models used in breast cancer studies, including scaffold-free (spheroid and organoid), scaffold-based, and chip-based models, particularly focused on the basic and translational application of these 3D models in drug screening and the tumor microenvironment in breast cancer. © 2022 American Chemical Society. All rights reserved.
Nabavi, S.M. ,
Karimi, S. ,
Arab, L. ,
Sanjari, L. ,
Mardpour, S. ,
Azimian, V. ,
Jarughi, N. ,
Ghaheri, A. ,
Hosseini, S. ,
Aghdami, N. Cell Journal (Yakhteh) (22285806) 23(7)pp. 772-778
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with very limited treatment options. Stem cells have been raised as a new treatment modality for these patients. We have designed a single-center, prospective, open-label, and single arm clinical trial to assess the safety, feasibility, and rather efficacy of administrating allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) in ALS patients. We enrolled 17 patients with confirmed ALS diagnosis with ALS Functional Rating Scale-Revised (ALSFRS-R) ≥24 and predicted forced vital capacity (FVC) ≥40%. Allogeneic Ad-MSCs were transplanted intravenously for all patients. Follow-ups were done at 24 hours, 2, 4, 6, and 12 months after cell infusion by checking adverse events, laboratory tests, and clinically by ALSFRS-R and FVC. Patients were also followed five years later and ALSFRS-R score was recorded in the survived individuals. There was no report of severe adverse events related to cell infusion. Two patients experienced dyspnea and chest pain 36 and 65 days after cell infusion due to pulmonary emboli. The progressive decrease in ALSFRS-R and FVC levels was recorded and three patients died in the first year. During five years follow up, despite a notable decrease in functional scores, 5 patients survived. Intravenous (IV) infusion of allogeneic Ad-MSCs in ALS patients is safe and feasible. The survival rate of the patients is more than IV autologous MSCs. © 2021 Royan Institute (ACECR). All rights reserved.
Azimian, V. ,
Dehghani-ghobadi, Z. ,
Ebrahimi, M. ,
Mirzazadeh, K. ,
Nazarenko, I. ,
Hossein, G. Scientific Reports (20452322) 11(1)
Wnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs) formation. We found here, that Wnt5A regulates differently the expression of its receptors in the stable Wnt5A overexpressing clones. The expression levels of Frizzled (FZD)-2 and -5, were increased in different clones. However ROR-1, -2 expression levels were differently regulated in clones. Wnt5A overexpressing clones showed increased cell proliferation, migration, and clonogenicity. Moreover, Wnt5A overexpressing SKOV-3 clone showed increased MCAs formation ability. Cell invasion had been increased in OVCAR-3-derived clones, while this was decreased in SKOV-3-derived clone. Importantly, αv integrin expression levels were increased in all assessed clones, accompanied by increased cell attachment to fibronectin and focal adhesion kinase activity. Moreover, the treatment of clones with Box5 as a Wnt5A/FZD5 antagonist abrogates ITGAV increase, cell proliferation, migration, and their attachment to fibronectin. Accordingly, we observed significantly higher expression levels of ITGAV and ITGB3 in human high-grade serous ovarian cancer specimens and ITGAV correlated positively with Wnt5A in metastatic serous type ovarian cancer. In summary, we hypothesize here, that Wnt5A/FZD-5 signaling modulate αv integrin expression levels that could be associated with ovarian cancer cell proliferation, migration, and fibronectin attachment. © 2021, The Author(s).
Keyghobadi, F. ,
Mehdipour, M. ,
Nekoukar, V. ,
Firouzi, J. ,
Kheimeh, A. ,
Nobakht lahrood, F. ,
Azimian, V. ,
Azimi, M. ,
Mohammadi, M. ,
Sodeifi, N. Frontiers in Oncology (2234943X) 10
Notch suppression by gamma-secretase inhibitors is a valid approach against melanoma. However, most of studies have evaluated the short-term effect of DAPT on tumor cells or even cancer stem cells. In the present study, we surveyed the short-term and long-term effects of DAPT on the stem cell properties of A375 and NA8 as melanoma cell lines. The effects of DAPT were tested both in vitro and in vivo using xenograft models. In A375 with B-raf mutation, DAPT decreased the level of NOTCH1, NOTH2, and HES1 as downstream genes of the Notch pathway. This was accompanied by enhanced apoptosis after 24 h treatment, arrest in the G2−M phase, and impaired ability of colony and melanosphere formation at the short term. Moreover, tumor growth also reduced during 13 days of treatment. However, long-term treatment of DAPT promoted tumor growth in the xenograft model and enhanced the number and size of colonies and spheroids in vitro. The gene expression studies confirmed the up-regulation of Wnt and Notch downstream genes as well as AXIN1, CSNK2A3, and CEBPA2 following the removal of Notch inhibitor in vitro and in the xenograft model. Moreover, the Gompertz-based mathematical model determined a new drug resistance term in the present study. Our data supported that the long-term and not short-term inhibition of Notch by DAPT may enhance tumor growth and motility through up-regulation of AXIN1, CSNK2A3, and CEBPA2 genes in B-raf mutated A375 cells. © Copyright © 2020 Keyghobadi, Mehdipour, Nekoukar, Firouzi, Kheimeh, Nobakht Lahrood, Azimian Zavareh, Azimi, Mohammadi, Sodeifi and Ebrahimi.
Nabavi, S.M. ,
Arab, L. ,
Jarooghi, N. ,
Bolurieh, T. ,
Abbasi, F. ,
Mardpour, S. ,
Azimian, V. ,
Moeininia, F. ,
Maroufizadeh, S. ,
Sanjari, L. Cell Journal (Yakhteh) (22285806) 20(4)pp. 592-598
Objective: Amyotrophic lateral sclerosis (ALS) is the most severe disorder within the spectrum of motor neuron diseases (MND) that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous (IV) and intrathecal (IT) injections of bone marrow derived mesenchymal stromal cells (BM-MSCs) in patients with ALS. Materials and Methods: This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale (ALS-FRS) ≥24, and ≥40% predicted forced vital capacity (FVC). All patients underwent bone marrow (BM) aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 (n=6) received an IV and patients in group 2 (n=8) received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging (MRI). In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection. Results: During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups. Conclusion: This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible (Registration numbers: NCT01759797 and NCT01771640). © 2019 Royan Institute (ACECR). All rights reserved.
Shadmanfar, S. ,
Labibzadeh, N. ,
Emadedin, M. ,
Jaroughi, N. ,
Azimian, V. ,
Mardpour, S. ,
Kakroodi, F.A. ,
Bolurieh, T. ,
Hosseini, S. ,
Chehrazi, M. Cytotherapy (14772566) 20(4)pp. 499-506
Background: In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625. Methods: This single-center, randomized, triple-blind, placebo-controlled phase 1/2 clinical trial randomized RA patients with knee involvement to receive either an intra-articular knee implantation of 40 million autologous bone marrow–derived MSCs per joint or normal saline (placebo). Patients were followed up for 12 months to assess therapy outcomes. Results: A total of 30 patients, 15 in the MSC group and 15 in the placebo group, enrolled in this study. There were no adverse effects reported after MSC administration or during follow-up. Patients who received MSCs had superior findings according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analogue scale (VAS), time to jelling and pain-free walking distance. However, this improvement could not be significantly sustained beyond 12 months. The MSC group exhibited improved standing time (P = 0.01). In addition, the MSCs appeared to contribute to reductions in methotrexate and prednisolone use. Conclusion: Intra-articular knee implantation of MSCs appeared to be safe and well tolerated. In addition, we observed a trend toward clinical efficacy. These results, in our opinion, have justified the need for further investigations over an extended assessment period with larger numbers of RA patients who have knee involvement. © 2018
Azimian, V. ,
Hossein, G. ,
Ebrahimi, M. ,
Dehghani-ghobadi, Z. Experimental Cell Research (10902422) 369(1)pp. 90-104
The present study investigated the role of Wnt11 in multicellular tumor spheroid-like structures (MCTS) ovarian cancer cell proliferation, migration and invasion in vitro and in vivo tumorigenesis and metastasis in xenograft nude mice model. Moreover, samples from human serous ovarian cancer (SOC) were used to assess the association of Wnt11 with integrins and cadherins. The data showed that Wnt11 overexpressing SKOV-3 cells became more compact accompanied by increased expression of E-and N-cadherin and lower expression of EpCAM and CD44. The α5, β2, β3 and β6 integrin subunits expression levels were significantly reduced in Wnt11 overexpressing cells accompanied with significantly reduced disaggregation of Wnt11 overexpressing SKOV-3 MCTS on ECM components. Moreover, Wnt11 overexpressing SKOV-3 MCTS showed decreased migration, invasion as well as no tumor growth and metastasis in vivo. We found that Wnt11 significantly and negatively correlated with ITGB2, ITGB6, and EpCAM and positively with CDH-1 in high-grade SOC specimens. Our results suggest that Wnt11 impedes MCTS attachment to ECM components and therefore can affect ovarian cancer progression. © 2018 Elsevier Inc.
Emadedin, M. ,
Labibzadeh, N. ,
Fazeli, R. ,
Mohseni, F. ,
Hosseini, S. ,
Moghadasali, R. ,
Mardpour, S. ,
Azimian, V. ,
Goodarzi, A. ,
Liastani, M.G. Cell Journal (Yakhteh) (22285806) 19(1)pp. 159-165
Objective: Nonunion is defined as a minimum of a 9-month period of time since an injury with no visibly progressive signs of healing for 3 months. Recent studies show that application of mesenchymal stromal cells (MSCs) in the laboratory setting is effective for bone regeneration. Animal studies have shown that MSCs can be used to treat nonunions. For the first time in an Iranian population, the present study investigated the safety of MSC implantation to treat human lower limb long bone nonunion. Materials and Methods: It is a prospective clinical trial for evaluating the safety of using autologus bone marrow derived mesenchymal stromal cells for treating nonunion. Orthopedic surgeons evaluated 12 patients with lower limb long bone nonunion for participation in this study. From these, 5 complied with the eligibility criteria and received MSCs. Under fluoroscopic guidance, patients received a one-time implantation of 20-50×106 MSCs into the nonunion site. All patients were followed by anterior-posterior and lateral X-rays from the affected limb, in addition to hematological, biochemical, and serological laboratory tests obtained before and 1, 3, 6, and 12 months after the implantation. Possible adverse effects that included local or systemic, serious or non-serious, and related or unrelated effects were recorded during this time period. Results: From a safety perspective, all patients tolerated the MSCs implantation during the 12 months of the trial. Three patients had evidence of bony union based on the after implantation X-rays. Conclusion: The results have suggested that implantation of bone marrow-derived MSCs is a safe treatment for nonunion. A double-blind, controlled clinical trial is required to assess the efficacy of this treatment (Registration Number: NCT01206179).
Sharifiaghdas, F. ,
Tajalli, F. ,
Taheri, M. ,
Naji, M. ,
Moghadasali, R. ,
Aghdami, N. ,
Baharvand, H. ,
Azimian, V. ,
Jaroughi, N. International Journal of Urology (14422042) 23(7)pp. 581-586
Objectives: To evaluate the effect of autologous muscle-derived cells injection in the treatment of complicated stress urinary incontinence in female patients. Methods: Female patients presenting with severe and complicated stress urinary incontinence secondary to the bladder neck and/or urethral trauma or congenital epispadias (with or without exstrophy) were enrolled in this prospective study. They underwent transurethral injection of autologous muscle-derived cells. In selected cases, another injection was given after 6 months, as per the surgeon's assessment. All patients were monitored for 1 year, and the effect of autologous muscle-derived cells was evaluated by cough stress test, 1-h pad test and Incontinence Impact Questionnaire-short form score. A multichannel urodynamic study and maximum urethral closure pressure were carried out before and 12 months after the last treatment session. Cough stress test, 1-h pad test and uroflowmetry were repeated 36 months after the last injection. Severity and occurrence of complications were recorded at each visit. Results: All 10 patients who completed the study were monitored for 36 months. Three patients were cured, four had improved and three did not respond to the treatment. There was no major adverse effect related to the treatment. Conclusions: Muscle-derived cell therapy might represent a minimally-invasive and a safe procedure in the treatment of patients with severe and complicated stress urinary incontinence. © 2016 The Japanese Urological Association
Mohamadnejad, M. ,
Vosough, M. ,
Moossavi, S. ,
Nikfam, S. ,
Mardpour, S. ,
Akhlaghpoor, S. ,
Ashrafi, M. ,
Azimian, V. ,
Jarughi, N. ,
Hosseini, S. Stem Cells Translational Medicine (21576564) 5(1)pp. 87-94
The present study assessed the effects of intraportal infusions of autologous bone marrow-derived mononuclear cells (MNCs) and/or CD133+ cells on liver function in patients with decompensated cirrhosis. We randomly assigned 27 eligible patients to a placebo, MNCs, and/or CD133+ cells. Cell infusions were performed at baseline and month 3. We considered the absolute changes in the Model for End-Stage Liver Disease (MELD) scores at months 3 and 6 after infusion as the primary outcome. The participants and those who assessed the outcomes were unaware of the treatment intervention assignments. After 6 months, 9 patients were excluded because of liver transplantation (n = 3), hepatocellular carcinoma (n = 1), loss to follow-up (n = 3), and death (n = 2). The final analysis included 4 patients from the CD133+ group, 8 from the MNC group, and 6 from the placebo group. No improvement was seen in the MELD score at month 6 using either CD133+ cells or MNC infusions compared with placebo. However, at month 3 after infusion, a trend was seen toward a higher mean absolute change in the MELD score in patients who had received CD133+ cells compared with placebo (−2.00 ± 1.87 vs. −0.13 ± 1.46; p = .08). No significant adverse events occurred in the present study. A transient improvement in the MELD score was observed in subjects treated with CD133+ cells but not in the MNC or placebo group. Although the study was not powered to make definitive conclusions, the data justify further study of CD133+ therapy in cirrhotic patients. © AlphaMed Press.
Labibzadeh, N. ,
Emadedin, M. ,
Fazeli, R. ,
Mohseni, F. ,
Hosseini, S. ,
Moghadassali, R. ,
Mardpour, S. ,
Azimian, V. ,
Liastani, M.G. ,
Bafghi, A.M. Cell Journal (Yakhteh) (22285806) 18(3)pp. 302-309
Objective: Nonunion is defned as a minimum of 9 months since injury without any visible progressive signs of healing for 3 months. Recent literature has shown that the application of mesenchymal stromal cells is safe, in vitro and in vivo, for treating long bone nonunion. The present study was performed to investigate the safety of mesenchymal stromal cell (MSC) implantation in combination with platelet lysate (PL) product for treating human long bone nonunion. Materials and Methods: In this case series clinical trial, orthopedic surgeons visited eighteen patients with long bone nonunion, of whom 7 complied with the eligibility criteria. These patients received mesenchymal stromal cells (20 million cells implanted once into the nonunion site using a?uoroscopic guide) in combination with PL product. For evaluation of the effects of this intervention all the patients were followed up by taking anterior-posterior and lateral X-rays of the affected limb before and 1, 3, 6, and 12 months after the implantation. All side effects (local or systemic, serious or non-serious, related or unrelated) were observed during this time period. Results: From a safety perspective the MSC implantation in combination with PL was very well tolerated during the 12 months of the trial. Four patients were healed; based on the control X-ray evidence, bony union had occurred. Conclusion: Results from the present study suggest that the implantation of bone marrow-derived MSCs in combination with PL is safe for the treatment of nonunion. A double blind, controlled clinical trial is required to assess the effcacy of this treatment (Registration Number: NCT01206179).
Vosough, M. ,
Moossavi, S. ,
Mardpour, S. ,
Akhlaghpoor, S. ,
Azimian, V. ,
Jarughi, N. ,
Hosseini, S. ,
Ashrafi, M. ,
Nikfam, S. ,
Aghdami, N. Archives Of Iranian Medicine (10292977) 19(2)pp. 131-136
Background: Transplantation of mesenchymal stem cells (MSCs) in combination with pioglitazone, an agonist of peroxisome prolifera-tor-activated receptor-y (PPAR-y), can reduce liver fibrosis in models of liver injury. In this study, we conducted a pilot study of intraportal infusion of autologous MSCs in combination with pioglitazone to assess safety, feasibility, and effectiveness in patients with compensated cirrhosis. Methods: Two patients with compensated cirrhosis were enrolled in this study. Intraportal autologous bone marrow-derived MSCs were transplanted twice (6 months interval) to the patients. Meanwhile, 30 mg/day pioglitazone was prescribed for 12 months. Patients were assessed at baseline and months 1, 3, 6, and 12 post-infusion. Results: Procedural complications or any major adverse effects did not occur in this pilot study. The patients' clinical conditions remained stable with no evidence of deterioration during the course of the study. A transient improvement in the Model for End-Stage Liver Disease (MELD) score was observed at month 3 post-infusion in one patient, which eventually returned to baseline at month 12. Conclusion: The combination of pioglitazone with MSCs is safe and feasible. The data justify further study of the combination therapy in cirrhotic patients. © 2016, Academy of Medical Sciences of I.R. Iran, INIA. All rights reserved.
Indian Journal of Pharmacology (02537613) 44(6)pp. 714-721
Objective: Glycogen synthase kinase-3β (GSK-3β) has been reported to be required for androgen receptor (AR) activity. This study sought to determine the usefulness of lithium chloride (LiCl) as a highly selective inhibitor of GSK-3β to increase the sensitivity of LNCap cells to doxorubicin (Dox), etoposide (Eto), and vinblastine (Vin) drugs. Materials and Methods: Thiazolyl Blue Tetrazolium Blue (MTT) assay was used to determine the cytotoxic effect to LiCl alone or in combination with low dose and IC 50 doses of drugs. Subsequently, cell cycle analysis was performed by using flow cytometry. Results: LiCl showed cytotoxic effect in a dose- and time-dependent manner (P<0.001). Both Dox (100 or 280 nM) and Vin IC 50 (5 nM) doses caused G2/M-phase arrest (P<0.001) compared with control. However, low dose (10 μM) or IC 50 (70 μM) Eto doses showed G2/M or S-phase arrests, respectively (P<0.001). Combination of low dose or IC50 dose of Eto with LiCl showed increased apoptosis as revealed by high percent of cells in SubG1 (P<0.05, P<0.01, respectively). Moreover, Eto (10 μM) led to decreased percent of cells in G2/M phase when combined with LiCl (P<0.05). Conclusion: This study showed that LiCl increases apoptosis of (LNCap) Lymph Node Carcinoma of the Prostate cells in the presence of Eto, which is S- and G2-phase-specific drug.
