جستجوی مقالات مرتبط با کلیدواژه « mesenchymal stem cells » در نشریات گروه « پزشکی »
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Objective (s)
Our previous study has showed that human amniotic mesenchymal stem cells (hAMSCs) transplantation improves neurological recovery after traumatic spinal cord injury (TSCI) in rats. However, less is known about the effects of exosomes derived from hAMSCs for TSCI. Here, we investigated whether hAMSCs-derived exosomes improve neurological recovery in TSCI rats and the underlying mechanisms.
Materials and MethodsA rat traumatic spinal cord injury (TSCI) mode was established using a weight drop device. At 2 hr after TSCI, rats were administered either hAMSCs-derived exosomes or phosphate buffered saline via the tail vein. Locomotor recovery was evaluated by an open-field locomotor rating scale and gridwalk task. Spinal cord water content, hematoxylin and eosin (H&E) staining, Evans blue (EB) dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were performed to elucidate the underlying mechanism.
ResultshAMSCs-derived exosomes significantly reduced the numbers of ED1+ macrophages/microglia and caspase-3+cells and decreased the levels of reactive oxygen species, myeloperoxidase activity and inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6 and interleukin-1β. In addition, hAMSCs-derived exosomes significantly attenuated spinal cord water content and Evans blue extravasation, and enhanced angiogenesis and axonal regeneration. Finally, hAMSCs-derived exosomes also significantly reduced the lesion volume, inhibited astrogliosis, and improved functional recovery.
ConclusionTaken together, these findings demonstrate that hAMSCs-derived exosomes have favourable effects on rats after acute TSCI, and that they may serve as an alternative cell-free therapeutic approach for treating acute TSCI.
Keywords: Angiogenesis, Exosomes, Mesenchymal Stem Cells, Neural Regeneration, Recovery Of Function} -
BackgroundResearchers are looking for a way to improve the myogenic differentiation of stem cells. Adipose-derived stem cells (ADSCs), known for their multipotency and regenerative capabilities, have been extensively studied for their therapeutic potential. Meanwhile, PC12 cells, derived from rat pheochromocytoma, have been found pivotal in neuroscience research, particularly as a neuronal model system. The current study investigated the effect of the PC12 adrenal pheochromocytoma cell line on the myogenic differentiation of ADSCs.MethodsThis experimental study was conducted during 2019-2022 (Ahvaz, Iran). Differentiation of ADSCs was induced by using 3 μg/mL 5-azacytidine for 24 hours. Then, the culture media was changed with Dulbecco’s Modified Eagle-High Glucose (DMEM-HG) containing 5% horse serum (HS) and kept for 7 days. Different percentages of differentiated ADSCs and PC12 (100:0, 70:30, 50:50, 30:70) were cocultured for 7 days in DMEM-HG containing 5% HS. PC12 was labeled with cell tracker C7000. The real-time polymerase chain reaction and Western blotting techniques were utilized to assess gene and protein expression. All experiments were repeated three times. Data were analyzed using GraphPad Prism 8.0.2 software with a one-way analysis of variance. P<0.05 was considered statistically significant.ResultsPC12 visualization confirmed the accuracy of the co-culture process. The differentiated cells showed an aligned, multinucleated shape. The differentiated ADSCs revealed significantly elevated levels of Myh1, Myh2, and Chrn-α1 gene expression compared with undifferentiated ADSCs (P<0.0001). The ADSCs cocultured with PC12 cells showed significantly higher Myh1, Myh2, and Chrn-α1 gene expression than differentiated ADSCs (P<0.001). ADSCs cocultured with 50% PC12 revealed significantly higher MYH and nAchR protein expression than the differentiated group (P<0.01 and P<0.001).ConclusionCoculturing PC12 cells and ADSCs improves the efficiency of myogenic differentiation. However, the effectiveness of myogenic differentiation depends on the proportions of administered PC12 cells.Keywords: Mesenchymal Stem Cells, PC12 Cells, Musculoskeletal Development, Coculture Techniques}
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Introduction
We recently discovered that microvesicles (MVs) derived from mesenchymal stem cells (MSCs) overexpressing miRNA-34a can alleviate experimental kidney injury in mice. In this study, we further explored the effects of miR34a-MV on renal fibrosis in the unilateral ureteral obstruction (UUO) models.
MethodsBone marrow MSCs were modified by lentiviruses overexpressing miR-34a, and MVs were collected from the supernatants of MSCs. C57BL6/J mice were divided into control, unilateral ureteral obstruction (UUO), UUO + MV, UUO + miR-34a-MV and UUO + miR-34a-inhibitor-MV groups. MVs were injected to mice after surgery. The mice were then euthanized on day 7 and 14 of modeling, and renal tissues were collected for further analyses by Hematoxylin and eosin (H&E), Masson’s trichrome, and Immunohistochemical (IHC) staining.
ResultsThe UUO + MV group exhibited a significantly reduced degree of renal interstitial fibrosis with inflammatory cell infiltration, tubular epithelial cell atrophy, and vacuole degeneration compared with the UUO group. Surprisingly, overexpressing miR-34a enhanced these effects of MSC-MV on the UUO mice.
ConclusionOur study demonstrates that miR34a further enhances the effects of MSC-MV on renal fibrosis in mice through the regulation of epithelial-to-mesenchymal transition (EMT) and Notch pathway. miR-34a may be a candidate molecular therapeutic target for the treatment of renal fibrosis.
Keywords: Microvesicles, Mesenchymal Stem Cells, Mir-34A, Obstruction, Renal Failure, Unilateral Ureteral} -
Objective (s)
Enhancement of proliferation, pluripotency, and self-renewal capacity as the unique features of MSCs can improve their therapeutic potential to regenerate tissues. In this context, crocin and curcumin, carotenoid compounds with outstanding medicinal properties, could be promising for cell protection and growth. This study aimed to evaluate the impact of nanocurcumin and crocin on BM-MSCs proliferation and pluripotency in vitro.
Materials and MethodsBM-MSC were isolated from the iliac crest of SCI patients who were candidates for stem cell therapy. The effect of crocin and nanocurcumin on MSC proliferation was evaluated using MTT and PDT assay. The percentage of apoptotic MSCs was measured by flow cytometry. Furthermore, mRNA and protein expression of OCT4 and SOX2 as the proliferation and self-renewal related genes were quantified by real-time PCR and western blotting, respectively.
ResultsOur findings demonstrated that only low concentrations of nanocurcumin (0.3 and 0.7 µM) and crocin (2.5 5 µM) significantly affected MSCs proliferation and protected them from apoptosis. Also, crocin and nanocurcumin at low doses caused an elevation in the mRNA and protein expression levels of OCT4 and SOX2 genes. In contrast, high concentrations decreased the survival of MSCs and led to increased apoptosis compared with the untreated group.
ConclusionOur results suggest that using nanocurcumin and crocin separately in culturing MSCs can be considered proliferative agents to prepare the more advantageous tool for cell therapies. However, more in vitro and preclinical research is needed in this area.
Keywords: Apoptosis, Cell Self Renewal, Cell Proliferation, Mesenchymal Stem Cells, Nanotechnology, Plant Extracts, Regenerative Medicine} -
International Journal of Hematology-Oncology and Stem Cell Research, Volume:18 Issue: 3, Jul 2024, PP 274 -284Background
Multiple myeloma (MM) is a malignancy of plasma cells, terminally differentiated B cells, with complications like hypercalcemia, renal failure, anemia, and bone disease, which are also known as CRAB criteria. MM develops from monoclonal gammopathy of unknown significance (MGUS), a pre-malignant plasma cell dyscrasia. Over some time, MGUS has the potential to progress into smoldering multiple myeloma (SMM), which can evolve into MM. MM rarely progresses into plasma cell leukemia (PCL), a condition in which malignant plasma cells no longer stay in the bone marrow niche and circulate in the peripheral blood. In MM, various soluble factors play important roles, and interleukin-6 has different vital roles. Interleukin-6, an inflammatory cytokine, has significant roles in the growth, survival, angiogenesis, metastasis, and apoptosis resistance in MM. Interleukin-6 is produced and secreted by both autocrine from myeloma cells and paracrine from bone marrow stromal cells. To tackle MM, various therapeutic approaches were applied over many years, and according to the results, most patients with MM can respond well to first-line treatment. However, the majority of patients may relapse as conventional treatment may not be curative. So, there is an urgent need for novel cell-based and cell-free therapeutic strategies, such as mesenchymal stem cell-based therapies and their products to offer new therapeutic strategies for MM.
Materials and MethodsIn the present study, we investigated the impacts of exosomes derived from human placental mesenchymal stem cells (hPMSCs) on apoptosis and interleukin-6 expression in a myeloma cell line, U-266, for the first time. hPMSCs were isolated from the human placenta and cultured in a DMEM medium. After characterizing the cells and acknowledging their identity, they underwent several passages and their supernatant was collected to harvest exosomes. The exosomes were isolated by ultracentrifugation and characterized by DLS and TEM, and their concentration was measured by BCA protein assay. U266 cells were treated with different concentrations of exosomes and then MTT and annexin/propidium iodide flow cytometry tests were performed to evaluate cell viability. Afterward, a real-time PCR test was performed to evaluate interleukin-6 gene expression.
ResultsAccording to our findings, treatment of U-266 cells with hPMSCS-derived exosomes led to the preservation of myeloma cells without changes in their cell cycle. Surprisingly, treatments did not hinder the expression of interleukin-6 in the myeloma cells.
ConclusionIn MM patients, interleukin-6 plays different roles, and it is a desirable target to design new therapeutic strategies. To evaluate the effects of new therapeutic strategies, we designed and performed our study to estimate the effects of cell-free therapeutic strategy. In the present study, the impacts of hPMSCS-derived exosomes on the viability of MM cells and interleukin-6 gene expression were evaluated. The results showed that hPMSCS-derived exosomes resulted in the perseverance of myeloma cells without changes in the cell cycle. Furthermore, the interleukin-6 gene expression level showed no significant change.
Keywords: Mesenchymal Stem Cells, Exosomes, Multiple Myeloma, Interleukin-6} -
Background
The aim of this study is to investigate the co-culture effects of human endometrial mesenchymal stem cells (EnMSCs) with mouse oocytes to enhance their maturation and development by using the hanging drop and sodium alginate hydrogel methods.
Materials and MethodsIn this experimental study, we prepared human EnMSCs (2.5×105 cells/mL) and co-cultured them with partially denuded mouse oocytes by the hanging drop (n=120) and sodium alginate hydrogel (n=120) methods. Control oocytes (n=230, total) were cultured in both systems in the absence of human EnMSCs for 18 hours. Both survival and maturation rates of the oocytes were analysed morphologically. After insemination with capacitated sperm, the fertilization and development of the embryos up to the blastocyst stage were assessed and compared statistically for all of the study groups via one-way ANOVA and the t tests.
ResultsOocytes cultured in the hanging drop method had a significantly higher survival rate than their control group (92.60 ± 4.36% vs. 84.20 ± 3.12%, P=0.018). There were no significant differences between the two experimental groups in terms of survival. The mean percent of oocytes that reached the metaphase II (MII) stage was 64.35 ± 3.19% and fertilised was 62.25 ± 4.43% in the hanging drop method; these rates were 63.43 ± 1.92% and 58.14 ± 4.14 in sodium alginate hydrogel method, respectively. These rates were higher than their controls (P<0.050), but there were no statistical differences between the two experimental groups (P>0.050). Among the studied groups, the highest significant blastocyst rate (32.55 ± 2.18%) was observed in the hanging drop experimental group (P=0.0017).
ConclusionThe results of this study show that human EnMSCs improve the survival, maturation, and development rates of oocytes and they could have future clinical applications.
Keywords: Co-Culture Techniques, In Vitro Maturation Of Oocyte, Mesenchymal Stem Cells, Sodium Alginate, 3-Dcell Culture} -
BackgroundAlzheimer’s disease (AD) is a neurodegenerative condition characterized by gradual cognitive impairment, including loss of synapses and nerve cells involved in learning, memory, and habit formation processes. Bone Marrow Mesenchymal Stem Cells (BM-MSCs) are multipotent cells. Because of their self-renewable, differentiation, and immunomodulatory capabilities, they are commonly used to treat many disorders. Hence, the current study intends to examine the effect of BM-MSCs transplantation on Aluminum chloride (AlCl3)-induced cognitive problems, an experimental model resembling AD’s hallmarks in rats.MethodsThe study was conducted in 2022 at The Biomedical Laboratory Faculty of Medicine, Andalas University, Indonesia. Adult male Wistar rats (three groups: negative control; no intervention+treatment with PBS; positive control: AlCl3+treatment with aqua dest; AlCl3+BM-MSCs: AlCl3+treatment with BM-MSCs, n=5 each) were treated daily with AlCl3 orally for five days. Stem cells were intraperitoneally injected into rats at a dose of 1x106 cells/rat. The same quantity of phosphate-buffered saline was given to the control group. One month after stem cell injection, the rat brain tissue was removed and placed in the film bottles that had been created. The expression of neural progenitor cell markers, including nestin and sex-determining Y-box 2 (SOX-2), was analyzed using real-time polymerase chain reaction (RT-PCR). Rats’ cognitive and functional memory were examined using Y-maze. Data were analyzed using SPSS software (version 26.0) with a one-way analysis of variance (ANOVA) test.ResultsThe gene expression of nestin (29.74±0.42), SOX-2 (31.44±0.67), and percent alternation of Y-maze (67.04±2.28) increased in the AlCl3+BM-MSCs group compared to that in the positive control group. RT-PCR analysis indicated that nestin (P<0.001) and SOX-2 (P<0.001) were significantly enhanced in the AlCl3+BM-MSCs group compared to the positive control group. This group also indicated an increased percent alternation of Y-maze (P<0.001) in the AlCl3+BM-MSCs group compared to the positive control group.ConclusionDue to its potential effects on cell therapy, BM-MSCs were found effective in a rat model of AD on the impairment of the rats’ behavior and increased expression of neural progenitor cell markers.Keywords: Mesenchymal Stem Cells, Neurodegenerative Diseases, Aluminum Chloride, Reverse Transcriptase Polymerase Chain Reaction, Nestin}
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Objective (s)
Skin aging is a degenerative process that can be induced by UV irradiation. UV radiation can produce reactive oxidate stress which causes premature aging. This study aims to examine the antiaging potential of secretome gel (SC) from human Wharton Jelly Mesenchymal Stem Cells (hWJ-MSCs) in a UVB-induced mice model.
Materials and MethodsThe secretome was obtained from hWJ-MSCs and made in gel form. Male mice were radiated by UVB for 15 min twice daily for 14 days. The gel was topically applied to the mice’s dorsal skin. Two treatments of secretome gel: secretome 1 is applied once and secretome 2 is applied twice daily after UVB radiation. TGF-β1, IL-10, and IL-18 gene expression was determined using RT-PCR. Hematoxylin Eosin staining was used to observe the inflammation and collagen density of skin tissue. An immunohistochemistry assay was used to analyze the protein expression of P53, COL4A1, MMP-2, and MMP-13. The data were statistically analyzed using the ANOVA test followed by the Tukey post hoc test (P<0.05).
ResultsUVB induction caused loss of collagen, increasing inflammation and high expression of aging mediators. SC increased the gene expression of TGF-β1 and IL-10 and decreased IL-18 gene expression. Histopathological tests showed that SG increased collagen density, lowered inflammation, and repaired cell damage in skin tissue. Immunohistochemistry test showed that SC decreased MMP-2, MMP-13, and P53 expression, in contrast, increased COL4A1.
ConclusionThe secretome gel of hWJ-MSCs showed antiaging activities with potential for preventing and curing skin aging.
Keywords: Inflammation, Mesenchymal stem cells, Oxidative stress, Secretome, Skin aging} -
Introduction
Although exogenous nitric oxide (NO) is used as medicine, in the previous we showed its inhibitory effect on the proliferation ability of rat bone marrow mesenchymal stem cells (BMSCs). In the present investigation, the inhibitory role of exogenous NO on BMSCs cell cycle was studied.
MethodsBMSCs after the third passage were treated for one hour every 48 hours with 100μM of sodium nitroprusside as an NO donor. Then, after 5,10,15, and 20 days of treatment, the viability, proliferation, and cell cycle of the BMSCs was investigated. In addition, the expression of the Raf1, CDK2, CDK4, P53, and GAPDH genes was studied.
ResultsCell treatment caused a significant reduction in viability and proliferation at 5,10,15, and 20 days. Also, the treatment caused cell cycle arrest at G1 after 20 days. In addition, it was found that the CDK2 and CDK4 expression were down-regulated whereas the P53 expression was up-regulated, but the expression of Raf1 as well as GAPDH remained the same.
ConclusionThis study showed that prolonged treatment with a NO donor arrest the BMSCs cell cycle due to overexpression of P53, which inhibits the expression of Cdk2 and Cdk4.
Keywords: Cell Cycle, Nitric Oxide, Mesenchymal Stem Cells, Cyclin-Dependent Kinases, Cell Proliferation} -
هدف
پوکی استخوان یک بیماری متابولیک مزمن است. کلریدکبالت (Cobalt (II) chloride; CoCl2) اثرات مطلوبی بر عملکرد سلول های بنیادی مزانشیمی مشتق شده از چربی انسانی (Human Adipose-Derived Mesenchymal Stem Cells; hAD-MSCs) ایجاد می کند. این مطالعه با هدف ارزیابی اثرات تزریق hAD-MSCs پره کاندیشن شده با کلریدکبالت جهت القاء هیپوکسی بر روی موش های صحرایی ماده مبتلا به پوکی استخوان ناشی از اوارکتومی انجام شد.
مواد و روش ها24 سر موش صحرایی ماده تحت جراحی اوارکتومی دو طرفه قرار گرفتند و بعد از 5/3 ماه، پیشرفت پوکی استخوان با استفاده از روش سی تی اسکن و با ارزیابی دانسیتومتری انجام شد. سپس، حیوانات به سه گروه شم (کنترل)، نورموکسی و هیپوکسی تقسیم شدند و به ترتیب فسفات بافر سالین (Phosphate Buffered Saline; PBS)، hAD-MSCs و hAD-MSCs پره کاندیشن شده با 100 میکرومول کلریدکبالت به مدت 48 ساعت را از طریق ورید دمی دریافت کردند. دو ماه بعد، نمونه برداری از استخوانهای تیبیا سمت راست و چپ جهت بررسی فاکتور القاء کننده هیپوکسی (Hypoxia-inducible factor-1α; HIF-1α) با روش وسترن بلات و هم چنین فاکتورهای رشد (Insulin-like Growth Factor; IGF1 و Transforming Growth Factor Beta; TGFβ) و سیتوکین های پیش التهابی (Tumor Necrosis Factor Alpha; TNFα و Interleukin-1beta; IL-1β) به روش Enzyme-Linked Immunosorbent Assay (ELISA) انجام شد.
یافته هادر گروه دریافت کننده hAD-MSCs پره کاندیشن شده با کلریدکبالت در مقایسه با گروه های دریافت کننده سلول های نورموکسی و PBS به ترتیب افزایش بیانHIF-1α (01/0<p و 001/0>P)، افزایش بیانIGF-I (01/0 P<و 001/0>P) و TGF-β (05/0<p و 01/0>P) و کاهش بیان TNF-α وIL-1β (001/0P< و 01/0>P) مشاهده شد.
نتیجه گیریکلریدکبالت منجر به افزایش کارایی و اثربخشی hAD-MSCs پره کاندیشن شده با کلریدکبالت بر افزایش ترشح فاکتورهای رشد و کاهش بیان سیتوکین های پیش التهابی از طریق افزایش بیان HIF-1α شد.
کلید واژگان: پوکی استخوان, هیپوکسی, کلرید کبالت, سلو ل های بنیادی مزانشیمی مشتق شده از چربی انسانی}Koomesh, Volume:25 Issue: 6, 2024, PP 679 -689IntroductionOsteoporosis (OP) is a chronic metabolic disease. Cobalt (II) chloride (CoCl2) induces favorable effects on hAD-MSCs (human Adipose-Derived Mesenchymal Stem Cells) function. This study aimed to assess the effects of CoCl2-preconditioned hAD-MSCs injection for hypoxia induction in female rats with ovariectomy-induced OP.
Materials and Methods24 adult female rats were subjected to bilateral ovariectomy. After 3.5 months, the OP progression was evaluated using CT scanning procedures with densitometric evaluation. Then, the animals were divided into 3 groups: sham (control), normoxia, and hypoxia groups receiving PBS (Phosphate Buffered Saline), hAD-MSCs, and 100 µM CoCl2-exposed hAD-MSCs for 48 h, respectively, via the tail vein. After 2 months, to investigate the hypoxia-inducing factor-1α (HIF-1α) by western blot analysis and to assess growth factors Insulin-like Growth Factor (IGF1) and Transforming Growth Factor Beta (TGFβ) and pro-inflammatory cytokines Tumor Necrosis Factor Alpha (TNFα) and Interleukin-1beta (IL-1β) using the ELISA (Enzyme-Linked Immunosorbent Assay) method, sampling of right and left tibia bone tissue markers was respectively done.
ResultsIn the group receiving 100 µM CoCl2-pretreated hAD-MSCs for 48 h, compared to the groups receiving normoxia cells and PBS, an increase in the expression of HIF-1α (P> 0.01 and P> 0.001), IGF-I (P> 0.01 and P>0.001), and TGF-β (P> 0.05 and P> 0.01), and a decrease in the expression of TNF-α and IL-1β (P> 0.001 and P>0.01) were significantly observed in right and left tibia bone, respectively.
ConclusionCoCl2 led to increased efficiency and effectiveness of CoCl2-pretreated hAD-MSCs in reducing the expression of pro-inflammatory cytokines and increasing growth factors through increasing the expression of HIF-1α.
Keywords: Osteoporosis, Hypoxia, Cobalt Chloride, Mesenchymal Stem Cells} -
IntroductionAn optimal culture medium that can rapidly and efficiently proliferate cells ex vivo is very crucial for developing mesenchymal stem cells (MSCs)-based tissue engineering and regenerative medicine. We developed a set of MSCs ex vivo proliferation medium, mscGOTM XF, which consists of a basal medium and a screened human platelet lysate.Materials and MethodsIn this study, the developed mscGOTM XF medium was prepared, and then testified by human MSCs isolated from bone marrow, umbilical cord, and fat tissue. The proliferation, surface markers, differentiation, and chromosomal stability of MSCs cultured in mscGOTM XF medium were investigated.ResultsThe mscGOTM XF medium could sustain MSCs at a high proliferation rate, with the population doubling time of 16 to 39 hours (depending on the type and passage number of MSCs). The proliferated MSCs could express CD105, CD90, and CD73, lack expression of CD34 and CD45; and maintain the capacity to differentiate into adipocytes, osteoblasts, and chondrocytes. Additionally, G-Band karyotyping data confirmed chromosome stability in the duration of cell culture at passage 5 and passage 7.ConclusionsThe mscGOTM XF medium could sustain MSCs proliferation ex vivo and exhibit the potential to be developed into a clinical-grade cell culture medium kit.Keywords: Xeno-Free Medium, Mesenchymal Stem Cells, Cell Proliferation, Cell Differentiation}
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In this article published in Cell J, Vol 24, No 12, 2022, on pages 741-747, the authors found that there was somemistakes in the Table 1 and we have corrected them in the following table.The authors would like to apologize for any inconvenience.
Keywords: Alginates, Cell Therapy, Encapsulation, Graphene Oxide, Mesenchymal Stem Cells} -
مجله دانشگاه علوم پزشکی شهید صدوقی یزد، سال سی و دوم شماره 2 (پیاپی 210، اردیبهشت 1403)، صص 7480 -7491مقدمه
زنان متعلق به گروه سنی باروری ممکن است با چالش هایی در مورد ناباروری یا سقط جنین به دلیل شرایطی مانند نارسایی زودرس تخمدان (POF) مواجه شوند. POF یک درصد از زنان زیر 40 سال را تحت تاثیر قرار می دهد که منجر به ناباروری می شود. تاکنون، داده ها نشان داده است که درمان POF با سلول های بنیادی در مقایسه با سایر گزینه ها موثرترین روش برای درمان POF است. استفاده از سلول های بنیادی مزانشیمی مشتق از بند ناف HUC-MSCs)) به دلیل ویژگی هایی مانند ایمنی زایی نسبتا کم، چند توانی (Multipotent)، منشا های چندگانه، مقرون به صرفه بودن، راحتی در تولید و کارایی بالا انتخاب خوبی برای درمان POF اولیه می باشد. این مطالعه مروری در نظر دارد تمام مزایا و معایبHUC-MSCs را به منظور درمان POF مورد بررسی قرار دهد.
نتیجه گیرییکی از راه های درمان POF استفاده از سلول های بنیادی مزانشیمی مشتق از بند ناف می باشد، این سلول ها ظرفیت فوق العاده ای را به منظور ترمیم و بازسازی دارند که این ویژگی به آن ها در ترمیم تخمدان های تحلیل رفته کمک می کند. نتایج این مقاله مروری نشان دهنده این است که استفاده از HUC-MSCs می تواند به عنوان یک روش درمانی بالقوه در درمان این بیماران مد نظر قرار گیرد.
کلید واژگان: یائسگی, زودرس, سلول های بنیادی مزانشیمی, ناباروری}Journal of Shaeed Sdoughi University of Medical Sciences Yazd, Volume:32 Issue: 2, 2024, PP 7480 -7491IntroductionWomen of reproductive age may encounter challenges related to infertility or miscarriage, due to conditions such as premature ovarian failure (POF). POF, affecting approximately one percent of women under the age of 40, can lead to infertility. Current data have suggested that utilizing stem cell therapy was the most effective approach for treating POF compared to alternative options. Among the various stem cell types, mesenchymal stem cells derived from the umbilical cord (HUC-MSCs) was a promising choice for treatment due to its features such as relatively low immunogenicity, multipotent, multiple origins, cost-effectiveness, ease of production, and high efficiency.
ConclusionOne of the ways to treat POF is the use of mesenchymal stem cells derived from the umbilical cord, these cells have an extraordinary capacity for repair and regeneration, which helps them in repairing depleted ovaries. The results of this review article indicate that the use of HUC-MSCs can be considered as a potential treatment method in these patients.
Keywords: Menopause, Premature, Mesenchymal Stem Cells, Infertility} -
Objective (s)
Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins.
Materials and MethodsBMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed.
ResultsThe results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group.
ConclusionThe results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis.
Keywords: Apoptosis, Mesenchymal stem cells, Conditioned medium, Myelin protein zero, Nerve growth factor, Sciatic nerve} -
ارزیابی تاثیر نانو ذرات پلاتینوم بر چرخه سلولی و بیان ژن های Sox-2 Oct-4 در سلول های بنیادی مزانشیمیپیش زمینه و هدف
سلول های بنیادی مزانشیمی (MSCs) گروهی از سلول های مهم قابل استفاده در سلول/ ژن درمانی هستند که نیاز به حفظ خواص بنیادینگی آن ها در سطح سلولی و مولکولی است تا عملکرد صحیح آن ها در کاربردهای پزشکی را تضمین نماید. یکی از موادی که کاربردهای مختلف در دنیای پزشکی دارد نانو ذرات پلاتینیوم می باشند. هدف از این کار بررسی تاثیر نانو ذرات پلاتینیوم بر چرخه سلولی و بیان ژن های Sox-2 و Oct-4 در سلول های بنیادی مزانشیمی در شرایط آزمایشگاهی بود.
مواد و روش کاردر این مطالعه تجربی، پس از سنتز نانو ذرات پلاتینوم، شکل و سایز دینامیکی آن ها با TEM و بار آن ها توسط تست DLS، چک گردید. سپس، کشت سلول های بنیادی مزانشیمی و زنده مانی آن ها پس از تیمار با نانو ذرات پلاتینیوم (pt) بررسی شد. علاوه بر این، میزان بیان ژن های Sox-2 و Oct-4 در سلول های تیمار شده با نانو ذرات ارزیابی شد. همچنین، اثرات نانو ذرات پلاتین بر چرخه سلولی و تشکیل کلنی در سلول های بنیادی مورد ارزیابی قرار گرفت. آنالیزهای آماری با نرم افزار Graph Pad prism نسخه 10 انجام گردید. سطح معنی داری p<0.05 تعریف گردید.
یافته هابر اساس نتایج به دست آمده، مورفولوژی نانو ذرات کروی و اندازه آن ها 180 نانومتر و بار آن ها +25.8 بود. تست سمیت سلولی نشان داد که اثرات این نانو ذرات ها بر سلول ها وابسته به دوز و زمان هستند. همچنین در حضور پلاتینیوم، چرخه سلولی سلول های بنیادی دچار تغییرات زیادی به ویژه افزایش درصد سلول ها در فاز S گردید. نتایج Real-time PCR نشان داد که در حضور نانو ذرات پلاتین، کاهش بیان ژن Sox-2 و Oct4 وجود دارد که منجر به کاهش خواص بنیادینگی سلول های بنیادی مزانشیمی شده است. همچنین پتانسیل کلون زایی آن ها نیز تضعیف شد.
بحث و نتیجه گیریدرمجموع، به دلیل اثرات منفی احتمالی نانو ذرات پلاتینیوم بر بنیادینگی MSCs، بایستی از نانو ذرات پلاتین در مصارف پزشکی طولانی مدت با احتیاط استفاده شود. لذا پیشنهاد می شوند دوز، دفعات و مدت زمان استفاده از نانو ذرات پلاتینوم حتی الامکان کاهش داده شود.
کلید واژگان: چرخه سلولی, سلول های بنیادی مزانشیمی, بیان ژن Oct-4, نانو ذرات پلاتین, بیان ژن Sox2}Background & AimsThe Mesenchymal Stem Cells (MSCs) are a population of widely used cells in cell/gene therapy which are necessary to maintain their stemness properties to guarantee their proper function in medical applications. Platinum nanoparticles are one of the materials that have various applications in the medical world. The aim of this work was to evaluate platinum nanoparticles effect on MSCs cell cycle and Oct-4 and Sox-2 expression in vitro.
Materials & MethodsIn this experimental study, after the synthesis of platinum nanoparticles, their dynamic shape and size were checked by TEM and their charge by DLS test. Then, the culture of mesenchymal stem cells and their survival after treatment with platinum nanoparticles (pt) were investigated. In addition, the expression levels of Sox-2 and Oct-4 genes were evaluated in cells treated with nanoparticles. Also, the effects of platinum nanoparticles on cell cycle and colony formation in stem cells were evaluated. Statistical analyzes were performed with Graph Pad Prism version 10 software. The significance level was defined as p<0.05.
ResultsBased on the obtained results, the morphology of spherical nanoparticles and their size was 180 nm and their charge was +25.8. Cytotoxicity test showed that the effects of these nanoparticles on cells are dose and time dependent. Also, in the presence of platinum, the cell cycle of stem cells underwent many changes, especially the increase in the percentage of cells in the S phase. Real-time PCR results showed that in the presence of platinum nanoparticles, there is a decrease in Sox-2 and Oct4 gene expression, which has led to a decrease in the stemness properties of mesenchymal stem cells. Also, their clonogenic potential was also weakened.
ConclusionWe concluded that due to the possible negative effects of platinum nanoparticles on the stemness of MSCs, platinum nanoparticles should be used with caution in long-term medical applications. Therefore, it is suggested to reduce the dose, frequency and duration of using platinum nanoparticles as much as possible.
Keywords: Cell Cycle, Mesenchymal Stem Cells, Oct-4 Expression, Platinum Nanoparticle, Sox-2 Expression} -
Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and self-tolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells. MSCs were harvested from human umbilical cord Wharton’s Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry. Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJ-MSCs derived exosome group and control group. Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells.
Keywords: Exosome, Mesenchymal Stem Cells, Regulatory T-Cells, Toll-Like Receptor3} -
International Journal of Hematology-Oncology and Stem Cell Research, Volume:18 Issue: 2, Apr 2024, PP 117 -122Background
miR-29c-3p manages a set of genes involved in regenerative medicine, and It seems that hyperglycemia in diabetic patients influences the power of stem cells to tissue regeneration the difficulties of diabetes by affecting the expression miR-29c-3p in mesenchymal stem cells. The study aims to analyze the effect of various glucose concentrations on the miR-29c-3p expression in mesenchymal stem cells.
Materials and MethodsAfter receiving donated mesenchymal stem cells from Tarbiat Modares University, these cells were cultivated in a DMEM culture medium, including three different concentrations of glucose 250, 140, and 100 mg/dl. RNA was extracted from these cells after 72 hours, the Real-Time PCR technique assessed the expression of miR-29c-3p, and the results were analyzed by REST software.
ResultsmiR-29c-3p expression in cells at concentrations of 140 and 250 mg/dL compared to typical situations (100 mg/dl) was significantly decreased (P˂0.05), which declined at a concentration of 250 mg/dl was more.
ConclusionReduced miR-29c-3p expression in mesenchymal stem cells in chronic and mild diabetic situations demonstrated that diabetes might be one of the significant reasons for mesenchymal stem cells' reduced ability to repair tissue damage.
Keywords: Diabetes, Mesenchymal stem cells, miR-29c-3p expression} -
Introduction
Stem cells isolated from the amniotic membrane can produce and release substances that can regenerate damaged tissues and contain proteins and other factors that via numerous major and minor mechanisms lead to increasing angiogenesis and tissue survival. This research was conducted to prove the defensive characteristics of the secretome in the face of temporary focal cerebral ischemia in mouse stroke models.
MethodsCerebral ischemia protocol in a specific area was implemented in rats with middle cerebral artery occlusion for 60 minutes and then reperfusion was given for 6, 20, and 30 minutes. Within 30 minutes after the start of reperfusion, conditioned medium derived from the human amniotic membrane (AMSC-CM) was poured into the right ventricle (ICV) at a dose of 0.5 µL. Finally, the volume of the injury, cerebral tissue water, sensorimotor activity, and the strength of the blood-brain barrier integrity were evaluated 24 hours after drug injection.
ResultsICV injection of conditioned medium at the start of reperfusion phase considerably decreased the volume of the injury 6, 20, and 30 hours after reperfusion compared to the MCAO-operated group (P<0.01). Cerebral tissue water in the treatment group decreased considerably after the intervention in comparison with the MCAO group in the core and penumbral area not in the subcortical area (P<0.05). Also, the amount of Evans blue infiltration at all times in the core and half-foot area in the AMSC-CM group was significantly reduced in parallel with the MCAO group (P<0.05).
ConclusionTreatment with AMSC-CM during 6-30 h after ischemia-reperfusion insult exerts some beneficial effects against ischemia-reperfusion injury. These findings provide an important vision for more complementary research and treatment of stroke.
Keywords: Conditioned medium, Mesenchymal Stem Cells, Blood-brain barrier, Stroke, Rats} -
Background
Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive destruction of behavioral and cognitive functions. Various therapies have been tested to improve or at least effectively change the course of AD. In recent years; stem cell therapy has emerged as a hopeful potential treatment for Alzheimer's. Stem cells can differentiate into various types of cells, including brain cells, potentially replacing damaged cells and improving cognitive function.
ObjectivesIn the present study we investigated the inhibitory effect of mesenchymal stem cells isolated from amniotic membrane (AM-MSCs) on neural progenitor cells (NPC) treated with Scopolamine.
MethodsNPC cell was provided by the Iranian Biological Resource Center. To expose these cells to Alzheimer's situations, scopolamine (0.05 mg/ml) treatment has been used. The inhibitory effect of mesenchymal stem cells isolated from the amniotic membrane was evaluated by using the co-cultivation method. The expression of amyloid beta (Aβ), TERM2, Tau, and ABCA7 genes, was assessed in NPC cells co-cultivated with AM-MSC by Real-time PCR. After the Co-culture of AM-MSC and NPC cells for 72 hours, we evaluated the expression of BDNF and CHAT protein in Co-cultured NPC cells by immunocytochemical test.
ResultsResults of Real-time PCR and Immunocytochemistry showed that in Co-culture of AM-MSC with NPC decreased Aß, TREM2, and Tau gene expression and increased ABCA7 expression. As well, the expression of BDNF and CHAT protein enhanced.
ConclusionsAM-MSCs have attracted much consideration. MSCs have the capability of immune regulation, regeneration, and neuroprotection These cells are a potential candidate for cell therapy due to their easy accessibility and compliance with ethical issues.
Keywords: Mesenchymal stem cells, neural progenitor cell, TERM2, Tau, Aβ, ABCA7} -
Background
The isolation of Mesenchymal Stem Cells (MSCs) from various tissues is possible, with the umbilical cord emerging as a competitive alternative to bone marrow. In order to fulfill the demands of cell therapy, it is essential to generate stem cells on a clinical scale while minimizing time, cost, and contamination. Here is a simple and effective protocol for isolating MSC from Wharton's Jelly (WJ-MSC) using the explant method with various supplements.
MethodsUtilizing the explant method, small fragments of Wharton's jelly from the human umbilical cord were cultured in a flask. The multipotency of the isolated cells, were confirmed by their differentiation ability to osteocyte and adipocyte. Additionally, the immunophenotyping of WJ-MSCs showed positive expression of CD73, CD90, and CD105, while remaining negative for hematopoietic markers CD34 and CD45, meeting the criteria for WJ-MSC identification. Following that, to evaluate cells' proliferative capacity, various supplements, including basic Fibroblast Growth Factor (bFGF), Non- Essential amino acids (NEA), and L-Glutamine (L-Gln) were added to either alpha- Minimal Essential Medium (α-MEM) or Dulbecco's Modified Eagle's Medium-F12 (DMEM-F12), as the basic culture media.
ResultsWJ-MSCs isolated by the explant method were removed from the tissue after seven days and transferred to the culture medium. These cells differentiated into adipocyte and osteocyte lineages, expressing CD73, CD90, and CD105 positively and CD34 and CD45 negatively. The results revealed that addition of bFGF to α-MEM or DMEMF12 media significantly increased the proliferation of MSCs when compared to the control group. However, there were no significant differences observed when NEA or LGln were added.
ConclusionAlthough bFGF considerably enhances cell proliferation, our study demonstrates that MSCs can grow and expand when properly prepared Wharton's jelly tissues of the human umbilical cord.
Keywords: Fibroblast growth factor 2, Mesenchymal stem cells, Umbilical cord}
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