Saeid Abroun - Academia.edu (original) (raw)
Papers by Saeid Abroun
Scientific Journal of Iran Blood Transfus Organ, 2015
Journal of Research in Applied and Basic Medical Sciences, Apr 10, 2020
International journal of medical laboratory, Feb 10, 2016
Bone marrow transplantation Hematopoietic Mobilization Stem cell Hematopoietic stem/progenitor ce... more Bone marrow transplantation Hematopoietic Mobilization Stem cell Hematopoietic stem/progenitor cells (HSPCs) which give rise to different blood cell types are present within the bone marrow microenvironment, especially in flat bones such as skull, vertebrae, pelvis and chest. Interacting factors such as stromal derived factor-1/CXCR4, very late antigen-4/vascular cell adhesion molecule-1, Lymphocyte function-associated antigen-1/ intercellular adhesion molecule-1 retain the cells in the microenvironment. Any factor affecting these links may lead to migration and mobilization of HSPCs into peripheral blood. Several factors are involved in hematopoietic stem cells (HSC) mobilization such as granulocyte-colony stimulating factor, sphingosine-1-phosphate, hepatocyte growth factor, complement system, plasminogen system and matrix metalloproteinases. In bone marrow transplantation, HSC is transferred to the recipient from bone marrow of the donor, which can be performed in two ways. In the first method, Jamshidi needle is used for aspiration of bone marrow to extract hematopoietic cells usually from the hip. The second method uses mobilizer factors such as granulocyte-colony stimulating factor and granulocyte-macrophage colony-stimulating factor to mobilize the HSC into peripheral blood. Mobilized hematopoietic stem cells are suitable for the bone marrow transplantation in leukemias such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocyte leukemia, Hairy cell leukemia, etc.
The neoplastic niche comprises complex interactions between multiple cell types and molecules req... more The neoplastic niche comprises complex interactions between multiple cell types and molecules requiring cell-cell signaling as well as local secretion. These niches are important for both the maintenance of cancer stem cells and the induction of neoplastic cells survival and proliferation. Each niche contains a population of tumor stem cells supported by a closely associated vascular bed comprising mesenchyme-derived cells and extracellular matrix. Targeting cancer stem cells and neoplastic niche may provide new therapies to eradicate tumors. Much progress has been very recently made in the understanding of the cellular and molecular interactions in the microenvironment of neoplastic niches. This review article provides an overview of the neoplastic niches in the bone marrow. In addition to highlighting recent advances in the field, we will also discuss components of the niche and their signaling pathways.
Experimental Oncology, Dec 22, 2018
Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood an... more Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood and bone marrow involvement, which is usually observed in older people. Genetic mutations, epigenetic changes and miRs play a role in CLL pathogenesis. Del 11q, del l17q, del 6q, trisomy 12, p53 and IgVH mutations are the most important genetic changes in CLL. Deletion of miR-15a and miR-16a can increase bcl2 gene expression, miR-29 and miR-181 deletions decrease the expression of TCL1, and miR-146a deletion prevents tumor metastasis. Epigenetic changes such as hypo-and hypermethylation, ubiquitination, hypo-and hyperacetylation of gene promoters involved in CLL pathogenesis can also play a role in CLL. Expression of CD38 and ZAP70, presence or absence of mutation in IgVH and P53 mutation are among the factors involved in CLL prognosis. Use of monoclonal antibodies against surface markers of B-cells like anti-CD20 as well as tyrosine kinase inhibitors are the most important therapeutic approaches for CLL.
Research Square (Research Square), Jan 27, 2021
Background: The epidemiological studies indicated that colorectal cancer is one of the most commo... more Background: The epidemiological studies indicated that colorectal cancer is one of the most common types of cancer in the world and is considered a leading cause of cancer-related death. The present study aimed to investigate the inhibitory effect of lactobacillus acidophilus supernatant (LAS) and lactobacillus rhamnosus supernatant (LRS) on the growth and invasiveness of the human colon carcinoma cell line (Caco2) in-vitro. Methods: In this experimental study, the anti-proliferative activity and anti-invasion potential of LAS and LRS were determined by MTT and transwell chambers assays, respectively. The expression of mitochondrial membrane potential-9 (MMP-9) and matrix metalloproteinase-12 (MMP12) genes were analyzed by real-time PCR. Results: The results indicated that supernatants of these two lactobacilli had cytotoxic effects on Caco-2 cells at a concentration of 25% v/v and higher. Thus, the minimum concentrations (25% V/V) of supernatants were chosen for further experiments. LAS and LRS could signi cantly suppress the invasiveness of Caco-2 cells. Also, the expression of MMP12 was signi cantly increased in Caco-2 cells when treated with LAS, whereas LRS had no signi cant effect on the invasive capacity and the gene expression levels of MMP12. The expression of MMP-9 was statistically decreased in Caco2 cells treated with LAS and LRS (P<0.00001). Conclusion: In general, it was shown that LAS and LRS exert anti-cancer activity against the growth, invasion, and metastasis of Caco2 cells in-vitro. It seems that these two bacteria could be used as prophylactic and therapeutic agents for the prevention and treatment of colorectal cancer.
Cell journal, Mar 7, 2023
Objective: Umbilical cord blood (UCB) is an accessible and effective alternative source for hemat... more Objective: Umbilical cord blood (UCB) is an accessible and effective alternative source for hematopoietic stem cell (HSC) transplantation. Although the clinical application of UCB transplantation has been increased recently, quantitative limitation of HSCs within a single cord blood unit still remains a major hurdle for UCB transplantation. In this study we used microcarrier beads to evaluate the ex vivo expansion of UCB-derived HSCs in co-cultured with UCB-derived mesenchymal stem cells (MSC). Materials and methods: In this experimental study, we used microcarrier beads to expand UCB-derived MSCs. We investigated the simultaneous co-culture of UCB-derived CD34+ cells and MSCs with microcarrier beads to expand CD34+ cells. The colony forming capacity and stemness-related gene expression on the expanded CD34+ cells were assessed to determine the multipotency and self-renewal of expanded cells. Results: Our results indicated that the microcarrier-based culture significantly increased the total number and viability of UCB-derived MSCs in comparison with the monolayer cultures during seven days. There was a significant increase in the UCB-derived CD34+ cells expanded in the presence of microcarrier beads in this co-culture system. The expanded UCB-derived CD34+ cells had improved clonogenic capacity, as evidenced by higher numbers of total colony counts, granulocyte, erythrocyte, monocyte, megakaryocyte colony forming units (CFU-GEMM), and granulocyte-monocyte colony forming units (CFU-GM). There were significantly increased expression levels of key regulatory genes (CXCR4, HOXB4, BMI1) during CD34+ cells self-renewal and quiescence in the microcarrier-based co-culture. Conclusion: Our results showed that the increase in the expansion and multipotency of CD34+ cells in the microcarrierbased co-culture can be attributed to the enhanced hematopoietic support of UCB-derived MSCs and improved cell-cell interactions. It seems that this co-culture system could have the potential to expand primitive CD34+ cells.
Cell journal, Mar 7, 2023
Objective: Beta-thalassemia is a group of inherited hematologic. The most HBB gene variant among ... more Objective: Beta-thalassemia is a group of inherited hematologic. The most HBB gene variant among Iranian beta-thalassemia patients is related to two mutations of IVSII-1 (G>A) and IVSI-5 (G>C). Therefore, our aim of this study is to use the knock in capability of CRISPR Cas9 system to investigate the correction of IVSII-1 (G>A) variant in Iran. Materials and methods: In this experimental study, following bioinformatics studies, the vector containing Puromycin resistant gene (PX459) was cloned individually by designed RNA-guided nucleases (gRNAs), and cloning was confirmed by sequencing. Proliferation of TLS-12 was done. Then, the transfect was set up by the vector with GFP marker (PX458). The PX459 vectors carrying the designed gRNAs together with Single-stranded oligodeoxynucleotides (ssODNs) as healthy DNA pattern were transfected into TLS-12 cells. After taking the single cell clones, molecular evaluations were performed on single clones. Sanger sequencing was then performed to investigate homology directed repair (HDR). Results: The sequencing results confirmed that all three gRNAs were successfully cloned into PX459 vector. In the transfection phase, The TLS-12 containing PX459-gRNA/ssODN was selected. Molecular evaluations showed that the HBB gene was cleaved by the CRISPR/Cas9 system, that indicates that the performance of non-homologous end joining (NHEJ) repair system. Sequencing in some clones cleaved by the T7E1 enzyme showed that HDR was not confirmed in these clones. Conclusion: IVS-II-1 (G> A) mutation, which is the most common thalassemia mutation especially in Iran, the CRISPR/ Cas9 system was able to specifically target the HBB gene sequence. This could even lead to a correction in the mutation and efficiency of the HDR repair system in future research.
Clinical Immunology
Evasion and suppression of immune surveillance allow neoplastic cells to survive and expand. This... more Evasion and suppression of immune surveillance allow neoplastic cells to survive and expand. This phenomenon is noticeable in multiple myeloma (MM) because reciprocal interactions between myeloma cells and the bone marrow's immune microenvironment are essential for disease development and progression [1]. For years, the conventional MM treatment regimen has consisted of chemotherapy with alkylating drugs (primarily melphalan) and hematopoietic stem cell transplantation (HSCT). Although in allogeneic HSCT (allo-HSCT), donor T cells can eliminate myeloma cells via the graft versus myeloma effect, this unspecific immunotherapy is not the priority due to the high morbidity and mortality rate [2]. Decades of research have led to enormous advances in MM treatment, from cytotoxic chemotherapies to novel targeting agents [1,3]. There is a wide range of active therapies for treating MM, comprising immunosuppressive drugs, immunomodulatory agents, monoclonal antibodies, proteasome inhibitors, and histone deacetylase inhibitors [4,5]. Although these immunotherapy agents significantly improve the life expectancy of refractory/relapsed MM patients, responses to the immunotherapy agents are not permanent due to the ability of myeloma cells to escape from immune responses. More innovative immunotherapy approaches should be tried in such cases, including CAR T cells, antibody-drug conjugates, and bispecific antibodies [6]. T cell-based immunotherapy is a promising option against MM in all stages of the disease, from newly diagnosed MM to relapsed/refractory MM [4]. Although CAR-T cell therapy is associated with favorable outcomes in MM treatment, it may result in life-threatening side effects such as severe neurotoxicity and cytokine release syndrome. Contrarily, immunotherapy with natural killer (NK) and CAR-NK cells results in less toxicity [2]. The present review discusses NK cells' interaction with the MM microenvironment, NK cell immunotherapies, potentials, challenges, and prospects of this novel immunotherapy.
Background and Objective: Long noncoding RNAs (lncRNAs) are a new class of non-coding RNAs that a... more Background and Objective: Long noncoding RNAs (lncRNAs) are a new class of non-coding RNAs that are currently being studied extensively. LncRNAs have many biological roles in gene expression, cell development and diseases. Recent studies showed that lncRNAs have an important role in cancers, including hematopoietic disorders which can be a tool for easier diagnosis and prognosis of many diseases and also a possible alternative treatment. This study investigates the expression of long non-coding RNA HOTAIR, in chronic myelogenous leukemia (CML). Materials and Methods: Peripheral blood samples were collected from 30 patients with CML and 20 healthy controls. The selected patients had no history of treatment and all patients were positive for BCR-ABL. Healthy controls were chosen based on similarity with the patients' age and gender and had no history of disease. Total RNA was extracted from the patients and healthy controls and HOTAIR gene expression levels were measured using qRT...
Objective: Chronic myeloid leukemia (CML) develops when a hematopoietic stem cell acquires the BC... more Objective: Chronic myeloid leukemia (CML) develops when a hematopoietic stem cell acquires the BCR/ABL fusion gene. This causes these transformed hematopoietic cells to have a greater than normal proliferation rate. Scientists attempt to improve the CML treatment process by silencing the BCR/ABL oncogene. In this work, we used morpholino antisense oligos to silence the BCR/ABL oncogene. Materials and Methods: In this study, the K562 was used as a BCR/ABL fusion-gene positive cell line and the Jurkat cell line as a control. We explored the inhibiting capacity of morpholino antisense oligos in the the expression of the BCR/ABL oncogene and studied their p210 BCR/ABL suppression, inhibition of cell proliferation and stimulation of apoptosis in the K562 cells after 24 and 48 hours. Endo-Porter was used for delivery of morpholino antisense oligos into cell cytosols. Meanwhile, flow cytometric analysis was performed in order to determine the appropriate concentration of morpholino antisen...
Medical laboratory sciences, 2016
Acute lymphoblastic leukemia(ALL) is due to early stage arrest of lymphoblast development. The tr... more Acute lymphoblastic leukemia(ALL) is due to early stage arrest of lymphoblast development. The translocation of Philadelphia (Ph) chromosome occurs as a result of the BCR-ABL fusion gene, which constitutively produced activated tyrosine kinase. This gene fusion is an important indicator for prognosis in ALL and is associated with poor overall survival and remission duration. BCR-ABL could interfere in establishment of ALL. Therefore, in this study, we will try to investigate most pathological aspects involved in BCR-ABL fusion. Strategies for genetic alterations in B-ALL pathogenesis are discussed. Then, the main cytogenetic changes and genetic subtypes for ALL are highlighted. Moreover, intermediate reactions between cancer stem cells (CSC) related to ALL, its niche and microenvironment is discussed. The main objective in this review is to understand the principle prognosis in ALL to introduce new approaches and treatment alternatives. K e y w o r ds: Acute lymphoblastic leukemia,...
Scientific Journal of Iran Blood Transfus Organ, 2015
Journal of Cellular Biochemistry, 2019
Aim: Umbilical cord blood hematopoietic stem cells (UCB HSCs) have been considered for the treatm... more Aim: Umbilical cord blood hematopoietic stem cells (UCB HSCs) have been considered for the treatment of hematological malignancies due to their noninvasive collection, greater capacity of expansion, and remarkable tolerance for HLA mismatch in transplantation. On the other hand, the most considerable limitation of these cells is their inadequate amount of CD34 + HSCs which leads to delayed engraftment. The aim of this study was the expansion of CD34 + HSCs by coculturing with mesenchymal stem cells (MSCs) overexpressing stromal cellderived factor-1, soluble and membrane isoforms of stem cell factor (sSCF/mSCF). Keeping structure and function of overexpressed cytokines by MSCs was expected which could beneficially affect the CD34 + HSC expansion. Methods: MSCs and CD34 + HSCs were isolated from UCB mononuclear cells. UCB MSCs were nucleofected with one or more of sSCF, mSCF, and SDF-1 expression vectors. Isolated CD34 + HSCs were then cocultured with nucleofected MSCs in 10 groups in culture medium containing TPO and Flt3L with or without SCF (3F or 2F groups). Then the CD34 + HSCs numeration, clonogenic capacity, and transcriptional levels of well-known HSCs regulatory and stemness genes (CXCR4, HOXB4, BMI1, and SALL4) were assessed following coculture with modified MSCs. Results: CD34 + HSCs which expanded on MSCs overexpressing mSCF/sSCF/ SDF-1 in the 3F group showed the most significant increase in the expansion (4.73 ± 0.26 fold), clonogenic capacity (5.3 ± 0.25 fold) and also transcriptional levels of CXCR4, HOXB4, and BMI1 (3.49 ± 0.13, 9.49 ± 0.78, and 11.6 ± 0.9 fold), respectively (P < 0.05). Conclusion: Overexpression of SCF and SDF-1 by UCB MSCs in coculture system has efficient effect on UCB HSCs expansion. Furthermore nucleofected MSC overexpressing either sSCF/mSCF or mSCF/ sSCF /SDF-1 could substitute the rhu SCF in HSC expansion culture medium.
Iranian South Medical Journal, 2016
Background: Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach for treatmen... more Background: Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB) has known as an alternative for hematopoietic stem/progenitor cells (HPSC) in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB). Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D) culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells' proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D) microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.
Background and Objectives Recently, circulating hematopoietic stem cells (HSC) have been used for... more Background and Objectives Recently, circulating hematopoietic stem cells (HSC) have been used for the treatment of most types of leukemia. However, the G-CSF mechanism has not been known yet but it is believed that G-CSF is mostly effective by its indirect functions. The suppression of the nervous system affects G-CSF induced mobilization of HSC. The main gene involved in mobilization is CXCR4 that ligand to SDF-1. So, this study investigates the effect of the main catecholamine of nervous system-Epinephrin-on CXCR4 expression. Materials and Methods In this experimental study, isolated cord blood CD34 + cell of 20 healthy newborn with MACs columns treated with 10 μM Epinephrine and 1 μM Proporanolol. Expression of CXCR4 has been investigated at 1, 3 and 5 hours with qRT-PCR. Receptors of beta adrenergic expression have been studied with RT-PCR. Results Beta adrenergic receptors are expressed on CD34 + cells. Epinephrine led to significantly increased CXCR4 in hours 1 (3.2 ± 0.5), 3 (2.4 ± 0.4) and 5 (2.2 ± 0.4). Cells treated with propranolol, return increased CXCR4 induced by epinephrine. Conclusions It can be concluded that G-CSF affects the expression of CXCR4 through increasing secretion of epinephrine in bone marrow with on beta adrenergic receptors. Cells with increased CXCR4 mobilized to release SDF-1 in peripheral blood.
Objective: Average Age of population in the industrial countries has increased. Because of aging ... more Objective: Average Age of population in the industrial countries has increased. Because of aging the percent of the diseases related to the oldness such as multiple myeloma have also increased. It has both common and unique symptoms and effects. The unique effects ...
Utilization of fetal hemoglobin inducing drugs is of crucial importance in novel therapeutic appr... more Utilization of fetal hemoglobin inducing drugs is of crucial importance in novel therapeutic approach of β-thalassemia and sickle cell disease. These drugs induce fetal hemoglobin production by several mechanisms such as increasing the proliferation and differentiation of erythroid progenitors. Thalidomide and sodium butyrate are two fetal hemoglobin inducers used as single and combination treatments.This research performed on erythroid progenitors derived from CD133+ cord blood stem cells. Flow cytometry was used for evaluation of the homogeneity of isolated CD133+ cells. Then, the colony formation potential of defined treated groups was evaluated using colony formation assay. Flow cytometry analysis showed the homogeneity of isolated CD133+ cord blood stem cells more than 95%. Also, the results of colony formation assay showed the potential of thalidomide in increasing the hematopoietic and erythroid colony count (1.3- and 1.5- fold increase, respectively) as compared to the control (p<0.05). The results of this study showed that thalidomide has a high potential in colony formation without cytotoxic effects on erythroid progenitors as compared to sodium butyrate and combination treatment (p<0.05). Keywords: beta-Thalassemia; Anemia, Sickle Cell; CD133+ stem cells; fetal Hemoglobin; Thalidomide; Sodium Butyrate.,
Scientific Journal of Iran Blood Transfus Organ, 2015
Journal of Research in Applied and Basic Medical Sciences, Apr 10, 2020
International journal of medical laboratory, Feb 10, 2016
Bone marrow transplantation Hematopoietic Mobilization Stem cell Hematopoietic stem/progenitor ce... more Bone marrow transplantation Hematopoietic Mobilization Stem cell Hematopoietic stem/progenitor cells (HSPCs) which give rise to different blood cell types are present within the bone marrow microenvironment, especially in flat bones such as skull, vertebrae, pelvis and chest. Interacting factors such as stromal derived factor-1/CXCR4, very late antigen-4/vascular cell adhesion molecule-1, Lymphocyte function-associated antigen-1/ intercellular adhesion molecule-1 retain the cells in the microenvironment. Any factor affecting these links may lead to migration and mobilization of HSPCs into peripheral blood. Several factors are involved in hematopoietic stem cells (HSC) mobilization such as granulocyte-colony stimulating factor, sphingosine-1-phosphate, hepatocyte growth factor, complement system, plasminogen system and matrix metalloproteinases. In bone marrow transplantation, HSC is transferred to the recipient from bone marrow of the donor, which can be performed in two ways. In the first method, Jamshidi needle is used for aspiration of bone marrow to extract hematopoietic cells usually from the hip. The second method uses mobilizer factors such as granulocyte-colony stimulating factor and granulocyte-macrophage colony-stimulating factor to mobilize the HSC into peripheral blood. Mobilized hematopoietic stem cells are suitable for the bone marrow transplantation in leukemias such as chronic myeloid leukemia, acute myeloid leukemia, chronic lymphocyte leukemia, Hairy cell leukemia, etc.
The neoplastic niche comprises complex interactions between multiple cell types and molecules req... more The neoplastic niche comprises complex interactions between multiple cell types and molecules requiring cell-cell signaling as well as local secretion. These niches are important for both the maintenance of cancer stem cells and the induction of neoplastic cells survival and proliferation. Each niche contains a population of tumor stem cells supported by a closely associated vascular bed comprising mesenchyme-derived cells and extracellular matrix. Targeting cancer stem cells and neoplastic niche may provide new therapies to eradicate tumors. Much progress has been very recently made in the understanding of the cellular and molecular interactions in the microenvironment of neoplastic niches. This review article provides an overview of the neoplastic niches in the bone marrow. In addition to highlighting recent advances in the field, we will also discuss components of the niche and their signaling pathways.
Experimental Oncology, Dec 22, 2018
Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood an... more Chronic lymphocytic leukemia (CLL) is increased proliferation of B-cells with peripheral blood and bone marrow involvement, which is usually observed in older people. Genetic mutations, epigenetic changes and miRs play a role in CLL pathogenesis. Del 11q, del l17q, del 6q, trisomy 12, p53 and IgVH mutations are the most important genetic changes in CLL. Deletion of miR-15a and miR-16a can increase bcl2 gene expression, miR-29 and miR-181 deletions decrease the expression of TCL1, and miR-146a deletion prevents tumor metastasis. Epigenetic changes such as hypo-and hypermethylation, ubiquitination, hypo-and hyperacetylation of gene promoters involved in CLL pathogenesis can also play a role in CLL. Expression of CD38 and ZAP70, presence or absence of mutation in IgVH and P53 mutation are among the factors involved in CLL prognosis. Use of monoclonal antibodies against surface markers of B-cells like anti-CD20 as well as tyrosine kinase inhibitors are the most important therapeutic approaches for CLL.
Research Square (Research Square), Jan 27, 2021
Background: The epidemiological studies indicated that colorectal cancer is one of the most commo... more Background: The epidemiological studies indicated that colorectal cancer is one of the most common types of cancer in the world and is considered a leading cause of cancer-related death. The present study aimed to investigate the inhibitory effect of lactobacillus acidophilus supernatant (LAS) and lactobacillus rhamnosus supernatant (LRS) on the growth and invasiveness of the human colon carcinoma cell line (Caco2) in-vitro. Methods: In this experimental study, the anti-proliferative activity and anti-invasion potential of LAS and LRS were determined by MTT and transwell chambers assays, respectively. The expression of mitochondrial membrane potential-9 (MMP-9) and matrix metalloproteinase-12 (MMP12) genes were analyzed by real-time PCR. Results: The results indicated that supernatants of these two lactobacilli had cytotoxic effects on Caco-2 cells at a concentration of 25% v/v and higher. Thus, the minimum concentrations (25% V/V) of supernatants were chosen for further experiments. LAS and LRS could signi cantly suppress the invasiveness of Caco-2 cells. Also, the expression of MMP12 was signi cantly increased in Caco-2 cells when treated with LAS, whereas LRS had no signi cant effect on the invasive capacity and the gene expression levels of MMP12. The expression of MMP-9 was statistically decreased in Caco2 cells treated with LAS and LRS (P<0.00001). Conclusion: In general, it was shown that LAS and LRS exert anti-cancer activity against the growth, invasion, and metastasis of Caco2 cells in-vitro. It seems that these two bacteria could be used as prophylactic and therapeutic agents for the prevention and treatment of colorectal cancer.
Cell journal, Mar 7, 2023
Objective: Umbilical cord blood (UCB) is an accessible and effective alternative source for hemat... more Objective: Umbilical cord blood (UCB) is an accessible and effective alternative source for hematopoietic stem cell (HSC) transplantation. Although the clinical application of UCB transplantation has been increased recently, quantitative limitation of HSCs within a single cord blood unit still remains a major hurdle for UCB transplantation. In this study we used microcarrier beads to evaluate the ex vivo expansion of UCB-derived HSCs in co-cultured with UCB-derived mesenchymal stem cells (MSC). Materials and methods: In this experimental study, we used microcarrier beads to expand UCB-derived MSCs. We investigated the simultaneous co-culture of UCB-derived CD34+ cells and MSCs with microcarrier beads to expand CD34+ cells. The colony forming capacity and stemness-related gene expression on the expanded CD34+ cells were assessed to determine the multipotency and self-renewal of expanded cells. Results: Our results indicated that the microcarrier-based culture significantly increased the total number and viability of UCB-derived MSCs in comparison with the monolayer cultures during seven days. There was a significant increase in the UCB-derived CD34+ cells expanded in the presence of microcarrier beads in this co-culture system. The expanded UCB-derived CD34+ cells had improved clonogenic capacity, as evidenced by higher numbers of total colony counts, granulocyte, erythrocyte, monocyte, megakaryocyte colony forming units (CFU-GEMM), and granulocyte-monocyte colony forming units (CFU-GM). There were significantly increased expression levels of key regulatory genes (CXCR4, HOXB4, BMI1) during CD34+ cells self-renewal and quiescence in the microcarrier-based co-culture. Conclusion: Our results showed that the increase in the expansion and multipotency of CD34+ cells in the microcarrierbased co-culture can be attributed to the enhanced hematopoietic support of UCB-derived MSCs and improved cell-cell interactions. It seems that this co-culture system could have the potential to expand primitive CD34+ cells.
Cell journal, Mar 7, 2023
Objective: Beta-thalassemia is a group of inherited hematologic. The most HBB gene variant among ... more Objective: Beta-thalassemia is a group of inherited hematologic. The most HBB gene variant among Iranian beta-thalassemia patients is related to two mutations of IVSII-1 (G>A) and IVSI-5 (G>C). Therefore, our aim of this study is to use the knock in capability of CRISPR Cas9 system to investigate the correction of IVSII-1 (G>A) variant in Iran. Materials and methods: In this experimental study, following bioinformatics studies, the vector containing Puromycin resistant gene (PX459) was cloned individually by designed RNA-guided nucleases (gRNAs), and cloning was confirmed by sequencing. Proliferation of TLS-12 was done. Then, the transfect was set up by the vector with GFP marker (PX458). The PX459 vectors carrying the designed gRNAs together with Single-stranded oligodeoxynucleotides (ssODNs) as healthy DNA pattern were transfected into TLS-12 cells. After taking the single cell clones, molecular evaluations were performed on single clones. Sanger sequencing was then performed to investigate homology directed repair (HDR). Results: The sequencing results confirmed that all three gRNAs were successfully cloned into PX459 vector. In the transfection phase, The TLS-12 containing PX459-gRNA/ssODN was selected. Molecular evaluations showed that the HBB gene was cleaved by the CRISPR/Cas9 system, that indicates that the performance of non-homologous end joining (NHEJ) repair system. Sequencing in some clones cleaved by the T7E1 enzyme showed that HDR was not confirmed in these clones. Conclusion: IVS-II-1 (G> A) mutation, which is the most common thalassemia mutation especially in Iran, the CRISPR/ Cas9 system was able to specifically target the HBB gene sequence. This could even lead to a correction in the mutation and efficiency of the HDR repair system in future research.
Clinical Immunology
Evasion and suppression of immune surveillance allow neoplastic cells to survive and expand. This... more Evasion and suppression of immune surveillance allow neoplastic cells to survive and expand. This phenomenon is noticeable in multiple myeloma (MM) because reciprocal interactions between myeloma cells and the bone marrow's immune microenvironment are essential for disease development and progression [1]. For years, the conventional MM treatment regimen has consisted of chemotherapy with alkylating drugs (primarily melphalan) and hematopoietic stem cell transplantation (HSCT). Although in allogeneic HSCT (allo-HSCT), donor T cells can eliminate myeloma cells via the graft versus myeloma effect, this unspecific immunotherapy is not the priority due to the high morbidity and mortality rate [2]. Decades of research have led to enormous advances in MM treatment, from cytotoxic chemotherapies to novel targeting agents [1,3]. There is a wide range of active therapies for treating MM, comprising immunosuppressive drugs, immunomodulatory agents, monoclonal antibodies, proteasome inhibitors, and histone deacetylase inhibitors [4,5]. Although these immunotherapy agents significantly improve the life expectancy of refractory/relapsed MM patients, responses to the immunotherapy agents are not permanent due to the ability of myeloma cells to escape from immune responses. More innovative immunotherapy approaches should be tried in such cases, including CAR T cells, antibody-drug conjugates, and bispecific antibodies [6]. T cell-based immunotherapy is a promising option against MM in all stages of the disease, from newly diagnosed MM to relapsed/refractory MM [4]. Although CAR-T cell therapy is associated with favorable outcomes in MM treatment, it may result in life-threatening side effects such as severe neurotoxicity and cytokine release syndrome. Contrarily, immunotherapy with natural killer (NK) and CAR-NK cells results in less toxicity [2]. The present review discusses NK cells' interaction with the MM microenvironment, NK cell immunotherapies, potentials, challenges, and prospects of this novel immunotherapy.
Background and Objective: Long noncoding RNAs (lncRNAs) are a new class of non-coding RNAs that a... more Background and Objective: Long noncoding RNAs (lncRNAs) are a new class of non-coding RNAs that are currently being studied extensively. LncRNAs have many biological roles in gene expression, cell development and diseases. Recent studies showed that lncRNAs have an important role in cancers, including hematopoietic disorders which can be a tool for easier diagnosis and prognosis of many diseases and also a possible alternative treatment. This study investigates the expression of long non-coding RNA HOTAIR, in chronic myelogenous leukemia (CML). Materials and Methods: Peripheral blood samples were collected from 30 patients with CML and 20 healthy controls. The selected patients had no history of treatment and all patients were positive for BCR-ABL. Healthy controls were chosen based on similarity with the patients' age and gender and had no history of disease. Total RNA was extracted from the patients and healthy controls and HOTAIR gene expression levels were measured using qRT...
Objective: Chronic myeloid leukemia (CML) develops when a hematopoietic stem cell acquires the BC... more Objective: Chronic myeloid leukemia (CML) develops when a hematopoietic stem cell acquires the BCR/ABL fusion gene. This causes these transformed hematopoietic cells to have a greater than normal proliferation rate. Scientists attempt to improve the CML treatment process by silencing the BCR/ABL oncogene. In this work, we used morpholino antisense oligos to silence the BCR/ABL oncogene. Materials and Methods: In this study, the K562 was used as a BCR/ABL fusion-gene positive cell line and the Jurkat cell line as a control. We explored the inhibiting capacity of morpholino antisense oligos in the the expression of the BCR/ABL oncogene and studied their p210 BCR/ABL suppression, inhibition of cell proliferation and stimulation of apoptosis in the K562 cells after 24 and 48 hours. Endo-Porter was used for delivery of morpholino antisense oligos into cell cytosols. Meanwhile, flow cytometric analysis was performed in order to determine the appropriate concentration of morpholino antisen...
Medical laboratory sciences, 2016
Acute lymphoblastic leukemia(ALL) is due to early stage arrest of lymphoblast development. The tr... more Acute lymphoblastic leukemia(ALL) is due to early stage arrest of lymphoblast development. The translocation of Philadelphia (Ph) chromosome occurs as a result of the BCR-ABL fusion gene, which constitutively produced activated tyrosine kinase. This gene fusion is an important indicator for prognosis in ALL and is associated with poor overall survival and remission duration. BCR-ABL could interfere in establishment of ALL. Therefore, in this study, we will try to investigate most pathological aspects involved in BCR-ABL fusion. Strategies for genetic alterations in B-ALL pathogenesis are discussed. Then, the main cytogenetic changes and genetic subtypes for ALL are highlighted. Moreover, intermediate reactions between cancer stem cells (CSC) related to ALL, its niche and microenvironment is discussed. The main objective in this review is to understand the principle prognosis in ALL to introduce new approaches and treatment alternatives. K e y w o r ds: Acute lymphoblastic leukemia,...
Scientific Journal of Iran Blood Transfus Organ, 2015
Journal of Cellular Biochemistry, 2019
Aim: Umbilical cord blood hematopoietic stem cells (UCB HSCs) have been considered for the treatm... more Aim: Umbilical cord blood hematopoietic stem cells (UCB HSCs) have been considered for the treatment of hematological malignancies due to their noninvasive collection, greater capacity of expansion, and remarkable tolerance for HLA mismatch in transplantation. On the other hand, the most considerable limitation of these cells is their inadequate amount of CD34 + HSCs which leads to delayed engraftment. The aim of this study was the expansion of CD34 + HSCs by coculturing with mesenchymal stem cells (MSCs) overexpressing stromal cellderived factor-1, soluble and membrane isoforms of stem cell factor (sSCF/mSCF). Keeping structure and function of overexpressed cytokines by MSCs was expected which could beneficially affect the CD34 + HSC expansion. Methods: MSCs and CD34 + HSCs were isolated from UCB mononuclear cells. UCB MSCs were nucleofected with one or more of sSCF, mSCF, and SDF-1 expression vectors. Isolated CD34 + HSCs were then cocultured with nucleofected MSCs in 10 groups in culture medium containing TPO and Flt3L with or without SCF (3F or 2F groups). Then the CD34 + HSCs numeration, clonogenic capacity, and transcriptional levels of well-known HSCs regulatory and stemness genes (CXCR4, HOXB4, BMI1, and SALL4) were assessed following coculture with modified MSCs. Results: CD34 + HSCs which expanded on MSCs overexpressing mSCF/sSCF/ SDF-1 in the 3F group showed the most significant increase in the expansion (4.73 ± 0.26 fold), clonogenic capacity (5.3 ± 0.25 fold) and also transcriptional levels of CXCR4, HOXB4, and BMI1 (3.49 ± 0.13, 9.49 ± 0.78, and 11.6 ± 0.9 fold), respectively (P < 0.05). Conclusion: Overexpression of SCF and SDF-1 by UCB MSCs in coculture system has efficient effect on UCB HSCs expansion. Furthermore nucleofected MSC overexpressing either sSCF/mSCF or mSCF/ sSCF /SDF-1 could substitute the rhu SCF in HSC expansion culture medium.
Iranian South Medical Journal, 2016
Background: Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach for treatmen... more Background: Hematopoietic stem cell transplantation (HSCT) is a therapeutic approach for treatment of hematological malignancies and incompatibility of Bone marrow. Umbilical cord blood (UCB) has known as an alternative for hematopoietic stem/progenitor cells (HPSC) in allogeneic transplantation. The low volume of collected samples is the main hindrance in application of HPSC derived from umbilical cord blood. So, ex vivo expansion of HPSCs is the useful approach to overcome this restriction. The goal of using this system is to produce appropriate amount of hematopoietic stem cells, which have the ability of transplantation and long term haematopoiesis. Material & Methods: In current study CD133+ cells were isolated from cord blood (CB). Isolated cells were seeded on microwells. Then expanded cells proliferation rate and ability in colony formation were assessed and finally were compared with 2 Dimensional (2D) culture systems. Results: Our findings demonstrated that CD133+ cells derived from UCB which were cultivated on microwells had significantly higher rate of proliferation in compared with routine cell culture systems. Conclusion: In Current study, it was shown that CD133+ cells' proliferations which were seeded on PDMS microwells coated with collagen significantly increased. We hope that 3 dimensional (3D) microenvironment which mimics the 3D structure of bone marrow can solve the problem of using UCB as an alternative source of bone marrow.
Background and Objectives Recently, circulating hematopoietic stem cells (HSC) have been used for... more Background and Objectives Recently, circulating hematopoietic stem cells (HSC) have been used for the treatment of most types of leukemia. However, the G-CSF mechanism has not been known yet but it is believed that G-CSF is mostly effective by its indirect functions. The suppression of the nervous system affects G-CSF induced mobilization of HSC. The main gene involved in mobilization is CXCR4 that ligand to SDF-1. So, this study investigates the effect of the main catecholamine of nervous system-Epinephrin-on CXCR4 expression. Materials and Methods In this experimental study, isolated cord blood CD34 + cell of 20 healthy newborn with MACs columns treated with 10 μM Epinephrine and 1 μM Proporanolol. Expression of CXCR4 has been investigated at 1, 3 and 5 hours with qRT-PCR. Receptors of beta adrenergic expression have been studied with RT-PCR. Results Beta adrenergic receptors are expressed on CD34 + cells. Epinephrine led to significantly increased CXCR4 in hours 1 (3.2 ± 0.5), 3 (2.4 ± 0.4) and 5 (2.2 ± 0.4). Cells treated with propranolol, return increased CXCR4 induced by epinephrine. Conclusions It can be concluded that G-CSF affects the expression of CXCR4 through increasing secretion of epinephrine in bone marrow with on beta adrenergic receptors. Cells with increased CXCR4 mobilized to release SDF-1 in peripheral blood.
Objective: Average Age of population in the industrial countries has increased. Because of aging ... more Objective: Average Age of population in the industrial countries has increased. Because of aging the percent of the diseases related to the oldness such as multiple myeloma have also increased. It has both common and unique symptoms and effects. The unique effects ...
Utilization of fetal hemoglobin inducing drugs is of crucial importance in novel therapeutic appr... more Utilization of fetal hemoglobin inducing drugs is of crucial importance in novel therapeutic approach of β-thalassemia and sickle cell disease. These drugs induce fetal hemoglobin production by several mechanisms such as increasing the proliferation and differentiation of erythroid progenitors. Thalidomide and sodium butyrate are two fetal hemoglobin inducers used as single and combination treatments.This research performed on erythroid progenitors derived from CD133+ cord blood stem cells. Flow cytometry was used for evaluation of the homogeneity of isolated CD133+ cells. Then, the colony formation potential of defined treated groups was evaluated using colony formation assay. Flow cytometry analysis showed the homogeneity of isolated CD133+ cord blood stem cells more than 95%. Also, the results of colony formation assay showed the potential of thalidomide in increasing the hematopoietic and erythroid colony count (1.3- and 1.5- fold increase, respectively) as compared to the control (p<0.05). The results of this study showed that thalidomide has a high potential in colony formation without cytotoxic effects on erythroid progenitors as compared to sodium butyrate and combination treatment (p<0.05). Keywords: beta-Thalassemia; Anemia, Sickle Cell; CD133+ stem cells; fetal Hemoglobin; Thalidomide; Sodium Butyrate.,