Publications by authors named "Somayeh Shahrokhi"

15 Publications

  • Page 1 of 1

Macrophage polarization in wound healing: role of aloe vera/chitosan nanohydrogel.

Drug Deliv Transl Res 2019 12;9(6):1027-1042

Department of Immunology, School of Medicine, Lorestan University of Medical Sciences, P.O. Box: 381351698, Khorramabad, Iran.

The balance between M1 and M2 macrophages plays an important role in wound healing. Interestingly, this immune response can be modulated by natural biomaterials such as chitosan nanohydrogel (Ch) and aloe vera (AV). Therefore, we aimed to improve wound recovery response by exploiting the potential healing properties of Ch and AV. Wounds were created in rats and were treated daily with either saline (control), AV, Ch, or different ratios of AV (volume):Ch (weight) (1:1), (2:1), and (3:1). M1 (iNOS, TNF-α) and M2 (CD163, TGF-β) responses were analyzed at days 3, 7, 14, 21, and 28. Wound healing increased within the third and seventh days in AV-Ch (3:1) (P < 0.001 and P < 0.002, respectively). In the treated groups, immunohistochemistry of iNOS expression decreased on the third day (P < 0.0001) while CD163 increased (P < 0.0001) on the 3rd, 7th, and 14th days. The gene expression of TGF-β decreased on the third day in AV group (P < 0.03) and on the 21st and 28th days in Ch-treated group (P < 0.00). TNF-α expression decreased in AV, Ch, and AV-Ch (3:1 v/w) on the 14th and 28th days (P < 0.00). TGF-β and TNF-α proteins decreased on the 28th day compared to the control and AV-Ch (3:1 v/w), respectively. AV-Ch (1 and 3:1 v/w) and Ch resulted in optimum wound repair by decreasing M1 after 3 days and increasing M2 after 14. Thus, Ch nanohydrogel, especially in combination with 1:1 and 1:3 ratio to AV, could be a proper candidate for modulating macrophages in response to wound healing.
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http://dx.doi.org/10.1007/s13346-019-00643-0DOI Listing
December 2019

Corrigendum to "Impact and Challenges of Mesenchymal Stem Cells in Medicine: An Overview of the Current Knowledge".

Stem Cells Int 2019 10;2019:5493654. Epub 2019 Mar 10.

Institute for Macromolecular Chemistry, Faculty of Chemistry and Pharmacy, BIOSS-Centre for Biological Signalling Studies, University of Freiburg, Hermann Staudinger Haus, Stefan-Meier Strasse 31, Freiburg D-79104, Germany.

[This corrects the article DOI: 10.1155/2018/5023925.].
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http://dx.doi.org/10.1155/2019/5493654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431428PMC
March 2019

Impact and Challenges of Mesenchymal Stem Cells in Medicine: An Overview of the Current Knowledge.

Stem Cells Int 2018 17;2018:5023925. Epub 2018 Dec 17.

Department of Cell Biology, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1155/2018/5023925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312597PMC
December 2018

CXCR4 expression is associated with time-course permanent and temporary myocardial infarction in rats.

Iran J Basic Med Sci 2017 Jun;20(6):648-654

Razi Herbal Medicines Research Center, Department of Physiology, Lorestan University of Medical Sciences, Khorramabad, Iran.

Objectives: Experimental myocardial infarction triggers secretion of Stromal cell-derived factor1 and lead to increase in the expression of its receptor "CXCR4" on the surface of various cells. The aim of this study was to evaluate the expression pattern of CXCR4 in peripheral blood cells following time-course permanent and temporary ischemia in rats.

Materials And Methods: Fourteen male Wistar rats were divided into two groups of seven and were placed under permanent and transient ischemia. Peripheral blood mononuclear cells were isolated at different time points, RNAs extracted and applied to qRT-PCR analysis of the CXCR4 gene.

Results: Based on repeated measures analysis of variance, the differences in the expression levels of the gene in each of the groups were statistically significant over time (the effect of time) (<0.001). Additionally, the difference in gene expression between the two groups was statistically significant (the effect of group), such that at all times, the expression levels of the gene were significantly higher in the permanent ischemia than in the transient ischemia group (<0.001). Moreover, the interactive effect of time-group on gene expression was statistically significant (<0.001).

Conclusion: CXCR4 is modulated in an induced ischemia context implying a possible association with myocardial infarction. Checking of CXCR4 expression in the ischemic changes shows that damage to the heart tissue trigger the secretion of inflammatory chemokine SDF, Followed by it CXCR4 expression in blood cells. These observations suggest that changes in the expression of CXCR4 may be considered a valuable marker for monitoring myocardial infarction.
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http://dx.doi.org/10.22038/IJBMS.2017.8832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501928PMC
June 2017

Evaluation of AD-MSC (adipose-derived mesenchymal stem cells) as a vehicle for IFN-β delivery in experimental autoimmune encephalomyelitis.

Clin Immunol 2016 08 1;169:98-106. Epub 2016 Jul 1.

Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran; Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Interferon-β (IFN-β) is commonly used as a disease modifying drug for the treatment of relapse-remitting multiple sclerosis (RR-MS). However, the underlying mechanism by which IFN-β mediate this immunosuppressive effect is still unknown. In this study, we analyzed the effects of genetically modified adipose-derived mesenchymal stem cells (AD-MSCs) expressing murine interferon beta (MSCs-VP/IFN-β) on the animal model of MS, experimental autoimmune encephalomyelitis (EAE). Lymph node mononuclear cells and serum were examined by using RT-PCR and ELISA methods to measure the production of IL-10 and IL-17 gene and protein expression, respectively. Our results indicated that in the MSCs-VP/IFN-β treated group induction of Tregs and IL-10 and reduction of IL-17 were significant. Taken together, we showed that using AD-MSCs expressing IFN-β as an anti-inflammatory agent, offer evidence supporting that the stem cell therapies in EAE conceivably will improve the valuable effects of IFN-β in this autoimmune disease.
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http://dx.doi.org/10.1016/j.clim.2016.06.015DOI Listing
August 2016

Immunomodulatory effects of adipose-derived mesenchymal stem cells on the gene expression of major transcription factors of T cell subsets.

Int Immunopharmacol 2014 Jun 3;20(2):316-21. Epub 2014 Apr 3.

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

It has been proposed that the immunomodulatory properties of mesenchymal stem cells (MSCs) play a crucial role in establishing and leading T lymphocytes, especially Th cell subsets, toward different functional subsets. To determine the effect of the immunomodulatory and regulatory functions of adipose-derived MSCs (AD-MSCs) on C57BL/6 spleen-isolated mononuclear cells (Spleen-MNCs), the gene expression of well-known effector and regulatory Th cell-related transcription factors, i.e., t-bet, GATA-3, Ror-γt and Foxp3, and their related cytokines, i.e., IFN-γ for Th1 cells, IL-4 for Th2 cells, IL-17 for Th17 cells and IL-10 and TGF-β for regulatory T cells, was studied using a co-culture condition system. The proliferation index of Spleen-MNCs was analyzed using a cell proliferation assay kit that utilized the CFSE staining method. Our findings indicate that AD-MSCs greatly impact the up-regulation of immunomodulatory cytokines, such as TGF-β (p<0.001), and the down-regulation of inflammatory cytokines, such as IFN-γ (p<0.005), and transcription factors, such as t-bet (p<0.001). Considering the immunomodulatory effects of MSCs in the differentiation of Th cell subsets, understanding and harnessing this property of MSCs could be a powerful strategy in the treatment of inflammatory autoimmune diseases such as multiple sclerosis.
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http://dx.doi.org/10.1016/j.intimp.2014.03.003DOI Listing
June 2014

Tumor necrosis factor-α/CD40 ligand-engineered mesenchymal stem cells greatly enhanced the antitumor immune response and lifespan in mice.

Hum Gene Ther 2014 Mar 4;25(3):240-53. Epub 2014 Mar 4.

1 Department of Immunology, School of Medicine, Lorestan University of Medical Sciences , Khorramabad, Iran 381351698.

The interaction between mesenchymal stem cells (MSCs) and dendritic cells (DCs) affects T cell development and function. Further, the chemotactic capacity of MSCs, their interaction with the tumor microenvironment, and the intervention of immune-stimulatory molecules suggest possible exploitation of tumor necrosis factor-α (TNF-α) and CD40 ligand (CD40L) to genetically modify MSCs for enhanced cancer therapy. Both DCs and MSCs were isolated from BALB/c mice. DCs were then cocultured with MSCs transduced with TNF-α and/or CD40L [(TNF-α/CD40L)-MSCs]. Major DCs' maturation markers, DC and T cell cytokines such as interleukin-4, -6, -10, -12, TNF-α, tumor growth factor-β, as well as T cell proliferation, were assessed. Meantime, a BALB/c mouse breast tumor model was inducted by injecting 4T1 cells subcutaneously. Mice (n = 10) in each well-defined test groups (n = 13) were cotreated with DCs and/or (TNF-α/CD40L)-MSCs. The controls included untreated, empty vector-MSC, DC-lipopolysaccharide, and immature DC mouse groups. Eventually, cytokine levels from murine splenocytes, as well as tumor volume and survival of mice, were assessed. Compared with the corresponding controls, both in vitro and in vivo analyses showed induction of T helper 1 (Th1) as well as suppression of Th2 and Treg responses in test groups, which led to a valuable antitumor immune response. Further, the longest mouse survival was observed in mouse groups that were administered with DCs plus (TNF-α/CD40L)-MSCs. In our experimental setting, the present pioneered study demonstrates that concomitant genetic modification of MSCs with TNF-α and CD40L optimized the antitumor immunity response in the presence of DCs, meantime increasing the mouse lifespan.
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http://dx.doi.org/10.1089/hum.2013.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955978PMC
March 2014

Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia.

Hematology 2013 Nov 20;18(6):315-22. Epub 2013 Feb 20.

University of Newcastle, Callaghan, New South Wales, Australia; Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.

Measurement of minimal residual disease (MRD) maintains an important role in the clinical management of acute lymphoblastic leukemia (ALL). Recently, we identified Fat1 cadherin as a unique and independent prognostic factor for relapse-free and overall survival in pediatric pre-B-ALL. Here, we analyzed Fat1 mRNA for its potential as a novel marker of MRD in cases of pre-B- and T-ALL. Analyses of microarray data from 125 matched diagnosis/relapse samples across three independent datasets indicate that Fat1 mRNA is detectable in an average of 31.3% of diagnosed pre-B-ALL, of which 67.5% of cases remained positive at relapse. Furthermore, some 20% of cases with undetectable levels of Fat1 mRNA at diagnosis became positive upon relapse. T-ALL cases were 83.3% positive for Fat1 expression at diagnosis with 77.7% remaining positive at relapse. Towards proof of concept, we developed a quantitative polymerase chain reaction assay and demonstrate detection of Fat1 mRNA in leukemic cells mixed with normal peripheral blood cells at a sensitivity of 1 in 10 000 to 100 000 cells. Fat1 may therefore provide a new marker of MRD for patients with ALL lacking known genomic aberrations or within a multiplex approach to MRD detection.
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http://dx.doi.org/10.1179/1607845413Y.0000000080DOI Listing
November 2013

Insights and hopes in umbilical cord blood stem cell transplantations.

J Biomed Biotechnol 2012 31;2012:572821. Epub 2012 Oct 31.

Department of Immunology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad 381351698, Iran.

Over 20.000 umblical cord blood transplantations (UCBT) have been carried out around the world. Indeed, UCBT represents an attractive source of donor hematopoietic stem cells (HSCs) and, offer interesting features (e.g., lower graft-versus-host disease) compared to bone marrow transplantation (BMT). Thereby, UCBT often represents the unique curative option against several blood diseases. Recent advances in the field of UCBT, consisted to develop strategies to expand umbilical stem cells and shorter the timing of their engraftment, subsequently enhancing their availability for enhanced efficacy of transplantation into indicated patients with malignant diseases (e.g., leukemia) or non-malignant diseases (e.g., thalassemia major). Several studies showed that the expansion and homing of UCBSCs depends on specific biological factors and cell types (e.g., cytokines, neuropeptides, co-culture with stromal cells). In this review, we extensively present the advantages and disadvantages of current hematopoietic stem cell transplantations (HSCTs), compared to UBCT. We further describe the importance of cord blood content and obstetric factors on cord blood selection, and report the recent approaches that can be undertook to improve cord blood stem cell expansion as well as engraftment. Eventually, we provide two majors examples underlining the importance of UCBT as a potential cure for blood diseases.
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http://dx.doi.org/10.1155/2012/572821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509718PMC
April 2013

Role of substance P (SP) and calcitonin gene-related peptide (CGRP) in gibbon-ape-leukemia virus (GALV) transduction of CD34+ cells.

Neuropeptides 2010 Dec 20;44(6):491-4. Epub 2010 Sep 20.

Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Aims: Optimization of transduction condition is an important goal to improve gene transduction. Therefore, we aimed to assess the effect of SP and/or CGRP as novel growth/transducing factors on the efficacy of CD34(+) transduction.

Methods: CD34(+) cells were transduced with Gibbon-Ape-Leukemia virus (GALV), containing Neomycin gene. CD34(+) cells were transduced with GALV presence of SP and/or CGRP. Real Time PCR and colony formation assay (CFU-C) was performed.

Results: Viral vectors titration on Hela cells indicated transduction efficiency of 1×10(6)CFU/ml. Real Time PCR of Neo and CFU-C showed stimulatory role of SP on gene transfer 5.9% and 14.84% compared to 3.6% and 12.58% in control group, while opposite role observed for CGRP 0.89% and 7.86%. Both SP and CGRP showed no significant effect in these assays.

Discussion: This study showed including of SP in growth factor cocktail is beneficial for CD34(+) transduction, which could be applied to genetic modification procedures.
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http://dx.doi.org/10.1016/j.npep.2010.08.002DOI Listing
December 2010

Communication of substance P, calcitonin-gene-related neuropeptides and chemokine receptor 4 (CXCR4) in cord blood hematopoietic stem cells.

Neuropeptides 2010 Oct;44(5):385-9

Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: Modulation of the expression of CXCR4 as a critical adhesion molecule on cord blood (CB) CD34+ cells could overcome delay following cord blood transplantation. Identification of beneficial effects of growth factors including cytokines and neuropeptides on CXCR4 expression would enable our understanding of this complicated network. Therefore, we aimed to assess the role of substance P (SP) and Calcitonin gene related peptide (CGRP) on CXCR4 levels.

Material And Methods: CD34+cells purified from CB were cultured in a serum-free liquid culture system. Different concentrations of SP and CGRP were used in combination with cytokine cocktail. Expression of CXCR4 at protein and genomic levels was assessed by flow cytometry and real time RT-PCR.

Results: Our results indicate increased CXCR4+ CD34+ cells after 7 days cultivation with SP and/or CGRP. Increased gene expression of the CXCR4 molecule was observed at 10(-9) M either SP or CGRP individually, by day 11 as compared to control group.

Conclusions: Our study indicates that SP and CGRP induce CXCR4 protein expression in short term culture, and stimulate its expression. Consequently, the increased expression of CXCR4 could improve engraftment of CB CD34+ cells.
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http://dx.doi.org/10.1016/j.npep.2010.06.002DOI Listing
October 2010

Effects of neuropeptide substance P on the expression of adhesion molecules in cord blood hematopoietic stem cells.

Ann Hematol 2010 Dec 17;89(12):1197-205. Epub 2010 Jun 17.

Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Modulation of adhesion molecules expression on the surface of cord blood (CB) CD34(+) cells may assist in overcoming the delay in cord blood engraftment. Likewise, utilization of diverse growth factors such as neuropeptides could also be helpful. Therefore, we aimed to assess the role of Substance P (SP) along with a cytokine cocktail on CB CD34(+) adhesion molecule expression. CB CD34(+) cells were cultured in a serum-free media containing different concentrations of SP in combination with a cytokine cocktail (SCF, FL, TPO, IL-3, and IL-6). Expression of adhesion molecules CXCR4, CD44, CD49e, and CD62L was analyzed after 7 and/or 11 days of cell cultivation. Additionally, the colonogenic capacity of cells was analyzed by colony formation unit assay. Our results show an enhanced percentage of CD34(+)cells with CXCR4, CD44, and CD62L on day 7, as compared with control. Furthermore, an increase in frequency was observed for CD49e(+) CD34(+)cells by day 7 in both test and control groups compared with day 0. Colonogenic assays show occurrence of more total colony formation and immature progenitor cells in SP-treated cells. Our study indicates that SP could act as an effective modulator for expression of cell adhesion molecules.
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http://dx.doi.org/10.1007/s00277-010-1006-1DOI Listing
December 2010

Gibbon ape leukemia virus transduction of peripheral blood CD34+-derived dendritic cells.

Hematol Oncol Stem Cell Ther 2010 ;3(1):399-402

Faculty of Paramedical Sciences, Tehran University of Medical Sciences, Tehran, Iran.

Background: Dendritic cells (DCs) play a critical role in the immune response and are a candidate for immunotherapy in cancer. Since gibbon ape leukemia virus (GALV) transduction of CD34+ cells is reasonably efficacious, we assessed the efficacy of GALV transduction of CD34+ derived DCs as a possible approach to creating genetically modified DCs for immunotherapy.

Methods: Peripheral blood CD34+ cells were transduced with retroviruses obtained from the PG13/LN C8 cell line, with the neomycin gene as a marker gene. After prestimulation of hematopoietic cells for 24 hours with 10 ng/mL interleukin (IL)-3, 10 ng/mL IL-6, 100 ng/mL stem cell factor, 100 ng/mL granulocyte-macrophage colony stimulating factor and 8 Amicrog/mL protamine sulfate, the cells were cultured in a transforming media prior to differentiating into DCs by GM-CSF, TNF-a and IL-4. Immunophenotyping analyses for confirmation of the generated DCs, colony formation assay and PCR were done for the expression of neomycin gene in the transduced cells.

Results: Titration of viral vectors indicated a transduction efficiency of 1×10(5) CFU/mL. Transduction efficiency for the CD34+ cells transformed to DCs was 45% and 38% before and after DC differentiation, respectively. Additionally, a mean (SEM) of 26.9% (11.4%) and 41.4% (11.8%) of the genetically modified DCs were positive for CD86+ HLA-DR and CD1a+CD14, respectively

Conclusion: This study showed that the majority of transduced CD34+ cells were successfully differentiated into cells identical to DCs according to morphology and immunophenotyping features, which could be a potential application in immunotherapy.
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February 2012

Substance P and calcitonin gene-related neuropeptides as novel growth factors for ex vivo expansion of cord blood CD34(+) hematopoietic stem cells.

Growth Factors 2010 Feb;28(1):66-73

Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

There is little evidence on roles of growth factors other than cytokines in expansion of cord blood (CB) stem cells. We aimed to explore a novel approach for expansion, using Substance P (SP) and calcitonin gene-related peptide (CGRP) neuropeptides. CB CD34(+) cells were cultured in different concentrations of SP and/or CGRP in combination with a cytokine cocktail. Phenotypic and functional analysis was performed by flowcytometry and colonogenic assay. Our results show a significant improvement of total expansion of neuropeptide treated cells. There was a selective effect of CGRP on CD34(+) CD133(+) cells, SP on CD34(+) CD45(dim) cells, and 10(- 9) M SP and/or CGRP on expansion of CD34(+) CD38(- ) cells. There was also a tendency for erythroid and granulocyte-myeloid colony formation in SP and CGRP treated cultures, respectively. Supplementation of cytokines with other growth factors, such as neuropeptides, might enable us to overcome the difficulties of ex vivo expansion of CB cells.
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http://dx.doi.org/10.3109/08977190903369404DOI Listing
February 2010

Low molecular weight fraction of shark cartilage can modulate immune responses and abolish angiogenesis.

Int Immunopharmacol 2005 Jun;5(6):961-70

Department of Immunology, School of Medical Sciences, Tarbiat Modarres University, P.O. Box: 14115-111, Tehran, IR Iran.

Shark cartilage has proven to have inhibitory effects on angiogenesis. In this research, we studied the effects of shark cartilage on the immune system. Firstly, we isolated and purified a shark cartilage protein fraction with the most immunostimulatory effects. Our fraction was composed of two proteins with molecular weights of about 14 and 15 kDa. This fraction highly augments delayed-type hypersensitivity response against sRBC in mice, and decreases the cytotoxic activity of Natural Killer cells. Furthermore, intraperitoneal injection of this fraction to tumor-bearing mice could increase T-cell infiltration into the tumor, and decrease the tumor lesion size. Also, this fraction has strong inhibitory effect on HBMEC proliferation and migration in fibrin matrix. According to these results, we suppose that this fraction is a good candidate for further studies in cancer therapy.
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http://dx.doi.org/10.1016/j.intimp.2005.01.006DOI Listing
June 2005