AIM:To improve hepatic differentiation of human mesenchymal stem cell(MSC)using insulin growth factor 1(IGF-Ⅰ),which has important role in liver development,hepatocyte differentiation and function.METHODS:Bone marrow...AIM:To improve hepatic differentiation of human mesenchymal stem cell(MSC)using insulin growth factor 1(IGF-Ⅰ),which has important role in liver development,hepatocyte differentiation and function.METHODS:Bone marrow of healthy donors was aspirated from the iliac crest.The adherent cells expanded rapidly and were maintained with periodic passages until a relatively homogeneous population was established.The identification of these cells was carried out by immunophenotype analysis and differentiation potential into osteocytes and adipocytes.To effectively induce hepatic differentiation,we designed a protocol based on a combination of IGF-Ⅰ and liver specificfactors(hepatocyte growth factor,oncostatin M and dexamethasone).Morphological features,hepatic functions and cytological staining were assessed to evaluate transdifferentiation of human marrow-derived MSCs.RESULTS:Flow cytometric analysis and the differentiation potential into osteoblasts and adipocytes showed that more than 90% of human MSCs which were isolated and expanded were positive by specif ic markers and functional tests.Morphological assessment and evaluation of glycogen storage,albumin and α-feto protein expression,as well as albumin and urea secretion revealed a statistically signif icant difference between the experimental groups and control.CONCLUSION:In vitro differentiated MSCs using IGF-Ⅰwere able to display advanced liver metabolic functions,supporting the possibility of developing them as potential alternatives to primary hepatocytes.展开更多
AIM: To improve the isolation and expansion of human marrow-derived mesenchymal stem cells (MSCs) based on rat samples. METHODS: Based on the fact that rat MSCs are relatively easy to obtain from a small aspirate, bon...AIM: To improve the isolation and expansion of human marrow-derived mesenchymal stem cells (MSCs) based on rat samples. METHODS: Based on the fact that rat MSCs are relatively easy to obtain from a small aspirate, bone marrow-derived MSCs from rat were cultured and characterized to set up the different protocols used in this study. Then, accordingly, almost the same protocols were performed on human healthy bone marrow samples, after obtaining approval of the ethics committee and gaining informed consent. We used different protocols and culture conditions, including the type of basal media and the culture composition. The MSCs were characterized by immunophenotyping and differentiation. RESULTS: There was no difference in morphology and proliferation capacity between different culture media at the first passage. During the 5-7th passages, the cells gradually lost their morphology and proliferation potential on Dulbecco’s modified Eagle’s medium (DMEM) high glucose and α modified Eagle’s medium. Although the cells expanded rapidly for up to 10 passages on DMEM low glucose containing 10% to 15% fetal calf serum (FCS), their proliferation was arrested without change in morphology and differentiation capacity at the third passage on 5% FCS. Flow cytometric analysis and functional tests confirmed that more than 90% of marrow cells which were isolated and expanded by our selective protocols were MSCs. CONCLUSION: We improved the isolation and expansion of human bone marrow derived MSCs, based on rat sample experiments, for further experimental and clinical use.展开更多
Lymphomas are a diverse group of haematologic malignancies, which occur in infection-fighting cells of the lymphatic system. Long non-coding RNAs (lncRNAs) are non-coding RNAs, which have recently received significant...Lymphomas are a diverse group of haematologic malignancies, which occur in infection-fighting cells of the lymphatic system. Long non-coding RNAs (lncRNAs) are non-coding RNAs, which have recently received significant attention as the main mediators of gene expression. In this review, we summarize the current knowledge on lncRNAs involved in lymphomas, their molecular functions, as well as their potential clinical value. Relevant literature was identified by a PubMed search of English language papers using the following terms: Lymphoma, LncRNA, leukemia, proliferation, apoptosis, and prognosis. LncRNAs are imperative for lymphoma carcinogenesis through affecting apoptosis, cell proliferation, invasion, and response to chemotherapy. The expression level of lncRNAs can affect chemotherapy-induced apoptosis. Taken together, lncRNA dysregulation in lymphoma cells is not only an epiphenomenon but also lncRNA transcription is critically related to the initiation and progression of lymphomas. Aberrant expression of lncRNAs can lead to the transformation of normal lymphocytes into lymphoma cells.展开更多
Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This stu...Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This study aimed to assess the safety and efficacy of usingmesenchymal stemcell(MSC)exosomes to treat refractory fistulas in patients with inflammatory bowel disease.Methods:MSCs were derived from the umbilical cords and their exosomes were isolated.Five patients with refractory perianal Crohn’s disease fistulas with amedian age of 35 years(range 31–47 years)were enrolled in the study.Exosome injections were administered in the operating roomto patients with refractory fistula(fistulas that are irresponsive to anti-tumor necrosis factor-αadministration within 6months).Sixmonths later,a physical examination,face-to-face interviews,andmagnetic resonance imaging were employed to evaluate the therapy responses of patients.Results:The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy.Three patients who received exosome injections exhibited complete healing,while one reported no improvement and active discharge from the fistula site.In addition,five patients(100%)reported neither systemic nor local adverse effects.Conclusions:Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect,as evidenced in this and other studies,and may play a significant role in the future treatment of gastrointestinal fistulas.展开更多
MicroRNAs （miRNAs） play an essential role in the development and progression of acute lymphoblastic leukemia （ALL）, and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lympho...MicroRNAs （miRNAs） play an essential role in the development and progression of acute lymphoblastic leukemia （ALL）, and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lymphoid differentiation has been here with discussed. However, the role of this miRNA in the outcome of ALL is not well understood. Peripheral blood of 48 patients with ALL and 20 age- and sex-matched healthy control subjects was used to accurately evaluate the expression of miR-146a by stem-loop Real time PCR. No statistically significant difference was found between patients and controls in total miR-146a expression. The expression of miR-146a was high （18.75%）, low （27.08~o） and not different （54.17%） in ALL patients. Our analysis indicated no association between the expression of miR-146a and any prognostic factors such as WBC/PLT counts, Hb, fusion genes （P190 and some translocations） with ALL type. This study revealed that miR-146a cannot be an independent factor for predicting the outcome of ALL patients. We suggest a multi-parameter analysis including miRNAs, transcription factors and critical genes to achieve a precise clinical panel for prognostic values.展开更多
BACKGROUND： Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lin...BACKGROUND： Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages. OBJECTIVE： This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis. METHODS： Relevant English-language studies were identified and retrieved from the PubMed search engine （1981-2017） using the following keywords： ＂Erythropoiesis＂, ＂Catecholamines＂, ＂Nervous system＂, and ＂Cytokines.＂ RESULTS： Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis. CONCLUSION： Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells （RBCs） in both chronic and physiological catecholamine activation.展开更多
基金Supported by A grant from Stem Cell Organization:www.stem cell.ir
文摘AIM:To improve hepatic differentiation of human mesenchymal stem cell(MSC)using insulin growth factor 1(IGF-Ⅰ),which has important role in liver development,hepatocyte differentiation and function.METHODS:Bone marrow of healthy donors was aspirated from the iliac crest.The adherent cells expanded rapidly and were maintained with periodic passages until a relatively homogeneous population was established.The identification of these cells was carried out by immunophenotype analysis and differentiation potential into osteocytes and adipocytes.To effectively induce hepatic differentiation,we designed a protocol based on a combination of IGF-Ⅰ and liver specificfactors(hepatocyte growth factor,oncostatin M and dexamethasone).Morphological features,hepatic functions and cytological staining were assessed to evaluate transdifferentiation of human marrow-derived MSCs.RESULTS:Flow cytometric analysis and the differentiation potential into osteoblasts and adipocytes showed that more than 90% of human MSCs which were isolated and expanded were positive by specif ic markers and functional tests.Morphological assessment and evaluation of glycogen storage,albumin and α-feto protein expression,as well as albumin and urea secretion revealed a statistically signif icant difference between the experimental groups and control.CONCLUSION:In vitro differentiated MSCs using IGF-Ⅰwere able to display advanced liver metabolic functions,supporting the possibility of developing them as potential alternatives to primary hepatocytes.
基金Supported by A grant from Stem Cell Organization: www.stem-cell.ir
文摘AIM: To improve the isolation and expansion of human marrow-derived mesenchymal stem cells (MSCs) based on rat samples. METHODS: Based on the fact that rat MSCs are relatively easy to obtain from a small aspirate, bone marrow-derived MSCs from rat were cultured and characterized to set up the different protocols used in this study. Then, accordingly, almost the same protocols were performed on human healthy bone marrow samples, after obtaining approval of the ethics committee and gaining informed consent. We used different protocols and culture conditions, including the type of basal media and the culture composition. The MSCs were characterized by immunophenotyping and differentiation. RESULTS: There was no difference in morphology and proliferation capacity between different culture media at the first passage. During the 5-7th passages, the cells gradually lost their morphology and proliferation potential on Dulbecco’s modified Eagle’s medium (DMEM) high glucose and α modified Eagle’s medium. Although the cells expanded rapidly for up to 10 passages on DMEM low glucose containing 10% to 15% fetal calf serum (FCS), their proliferation was arrested without change in morphology and differentiation capacity at the third passage on 5% FCS. Flow cytometric analysis and functional tests confirmed that more than 90% of marrow cells which were isolated and expanded by our selective protocols were MSCs. CONCLUSION: We improved the isolation and expansion of human bone marrow derived MSCs, based on rat sample experiments, for further experimental and clinical use.
文摘Lymphomas are a diverse group of haematologic malignancies, which occur in infection-fighting cells of the lymphatic system. Long non-coding RNAs (lncRNAs) are non-coding RNAs, which have recently received significant attention as the main mediators of gene expression. In this review, we summarize the current knowledge on lncRNAs involved in lymphomas, their molecular functions, as well as their potential clinical value. Relevant literature was identified by a PubMed search of English language papers using the following terms: Lymphoma, LncRNA, leukemia, proliferation, apoptosis, and prognosis. LncRNAs are imperative for lymphoma carcinogenesis through affecting apoptosis, cell proliferation, invasion, and response to chemotherapy. The expression level of lncRNAs can affect chemotherapy-induced apoptosis. Taken together, lncRNA dysregulation in lymphoma cells is not only an epiphenomenon but also lncRNA transcription is critically related to the initiation and progression of lymphomas. Aberrant expression of lncRNAs can lead to the transformation of normal lymphocytes into lymphoma cells.
文摘Background:Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stemcells.This study aimed to assess the safety and efficacy of usingmesenchymal stemcell(MSC)exosomes to treat refractory fistulas in patients with inflammatory bowel disease.Methods:MSCs were derived from the umbilical cords and their exosomes were isolated.Five patients with refractory perianal Crohn’s disease fistulas with amedian age of 35 years(range 31–47 years)were enrolled in the study.Exosome injections were administered in the operating roomto patients with refractory fistula(fistulas that are irresponsive to anti-tumor necrosis factor-αadministration within 6months).Sixmonths later,a physical examination,face-to-face interviews,andmagnetic resonance imaging were employed to evaluate the therapy responses of patients.Results:The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy.Three patients who received exosome injections exhibited complete healing,while one reported no improvement and active discharge from the fistula site.In addition,five patients(100%)reported neither systemic nor local adverse effects.Conclusions:Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect,as evidenced in this and other studies,and may play a significant role in the future treatment of gastrointestinal fistulas.
文摘MicroRNAs （miRNAs） play an essential role in the development and progression of acute lymphoblastic leukemia （ALL）, and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lymphoid differentiation has been here with discussed. However, the role of this miRNA in the outcome of ALL is not well understood. Peripheral blood of 48 patients with ALL and 20 age- and sex-matched healthy control subjects was used to accurately evaluate the expression of miR-146a by stem-loop Real time PCR. No statistically significant difference was found between patients and controls in total miR-146a expression. The expression of miR-146a was high （18.75%）, low （27.08~o） and not different （54.17%） in ALL patients. Our analysis indicated no association between the expression of miR-146a and any prognostic factors such as WBC/PLT counts, Hb, fusion genes （P190 and some translocations） with ALL type. This study revealed that miR-146a cannot be an independent factor for predicting the outcome of ALL patients. We suggest a multi-parameter analysis including miRNAs, transcription factors and critical genes to achieve a precise clinical panel for prognostic values.
文摘BACKGROUND： Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages. OBJECTIVE： This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis. METHODS： Relevant English-language studies were identified and retrieved from the PubMed search engine （1981-2017） using the following keywords： ＂Erythropoiesis＂, ＂Catecholamines＂, ＂Nervous system＂, and ＂Cytokines.＂ RESULTS： Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis. CONCLUSION： Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells （RBCs） in both chronic and physiological catecholamine activation.
