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28 May 2023, Volume 27 Issue 15 Previous Issue    Next Issue

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Effects of beta-catenin gene silencing on stemness transcription factors in hepatocellular carcinoma stem cells Sun Hua, Qin Yanchun, Rong Zhen, Li Zulong, Jiang Ruiyuan, Zhong Xiaoting, Mo Chunmei 2023, 27 (15):  2297-2303.  doi: 10.12307/2023.364 Abstract ( 340 )   PDF (1941KB) ( 63 )   Save BACKGROUND: Hepatocellular carcinoma stem cell is responsible for the formation, renewal and proliferation of cancer cells. It is a major topic to find key targets for hepatocellular carcinoma stem cell therapy and to further expand comprehensive treatment means for liver cancer. OBJECTIVE: To observe changes of stemness transcription factors after β-catenin gene silencing on CD133+HepG2 cells, and investigate the action mechanism of β-catenin regulating stemness of hepatocellular carcinoma stem cells.  METHODS: After CD133+HepG2 hepatocellular carcinoma stem cells were screened by magnetic activated cell sorting, these cells were induced and cultured in stem cell culture medium. Positive rate of CD133+HepG2 hepatocellular carcinoma stem cells was identified by flow cytometry. β-Catenin shRNA lentiviral plasmid was constructed to inhibit β-catenin expression by RNA interference. After transfected CD133+HepG2 hepatocellular carcinoma stem cells for 72 hours, plasmid was labeled with fluorescence, which evaluated transfection efficiency. After β-catenin silencing was confirmed, CD133+HepG2 hepatocellular carcinoma stem cell proliferation was measured by plate clone formation assay. CD133+HepG2 hepatocellular carcinoma stem cell cycle was detected by flow cytometry. RT-PCR and western blot assay were used to detect the mRNA and protein expression of stemness transcription factors SOX2, NANOG and OCT4.  RESULTS AND CONCLUSION: Compared with blank control group and virus-free group, clone formation ability was decreased in virus-blockade group. Percentage of G0/G1 phase cells increased significantly, while that of S phase cells and G2/M phase cells decreased. Protein and mRNA expression of NANOG, SOX2 and OCT4 was significantly decreased in virus-blockade group (P < 0.05). It is indicated that down-regulation of β-catenin expression may have a potential effect on suppressing the stemness of hepatocellular carcinoma stem cells. Figures and Tables | References | Related Articles | Metrics

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Valproic acid promotes osteogenic differentiation of rat bone marrow mesenchymal stem cells Ling Xuwei, Sun Jie, Liu Chang, Wang Yi, Shi Qin, Yang Huilin 2023, 27 (15):  2304-2310.  doi: 10.12307/2023.365 Abstract ( 351 )   PDF (1974KB) ( 47 )   Save BACKGROUND: Valproic acid, as a histone deacetylase inhibitor, has the ability to promote osteogenic differentiation of cells, but the mechanism is still unclear. OBJECTIVE: To investigate the effect and mechanism of valproic acid on osteogenic differentiation of rat bone marrow mesenchymal stem cells.  METHODS: Bone marrow mesenchymal stem cells were isolated from Sprague-Dawley rats and identified by flow cytometry. CCK-8 assay was used to detect the effects of different concentrations of valproic acid on the proliferation of rat bone marrow mesenchymal stem cells, and determine the used concentration of valproic acid. After adding valproic acid, rat bone marrow mesenchymal stem cells were induced to osteogenic differentiation. Alkaline phosphatase staining was performed on day 7 of osteogenic induction culture, and alizarin red staining was performed on day 21 of osteogenic induction culture. Quantitative real-time polymerase chain reaction was used to detect the expression of osteogenesis-related genes and EZH2 on days 3 and 7 of osteogenic induction culture. The protein expression levels of Runt-related transcription factor 2, EZH2 and H3K27me3 were detected by western blot assay on day 5 of osteogenic induction culture.  RESULTS AND CONCLUSION: (1) CCK-8 cell proliferation assay showed that bone marrow mesenchymal stem cell proliferation was significantly inhibited by increasing the concentration of valproic acid. (2) The results of alkaline phosphatase staining and alizarin red staining showed that valproic acid could increase the expression of alkaline phosphatase and enhance the ability of bone mineralization. (3) qRT-PCR results showed that valproic acid could increase the expression of osteogenesis-related genes and decrease the expression of EZH2 gene. (4) Western blot assay results showed that valproic acid could increase the expression of Runt-related transcription factor 2 protein and decrease the expression of EZH2 and H3K27me3 protein. (5) It is concluded that valproic acid can promote osteogenic differentiation of rat bone marrow mesenchymal stem cells by down-regulating EZH2 expression.  Figures and Tables | References | Related Articles | Metrics

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Efficient removal of a decellularized reagent sodium dodecyl sulfate in allogeneic tissue Hu Kai, Li Miao, Shao Yiran, Wang Jingjing, Chen Jinfa 2023, 27 (15):  2311-2317.  doi: 10.12307/2023.617 Abstract ( 334 )   PDF (2948KB) ( 112 )   Save BACKGROUND: Sodium dodecyl sulfate is commonly used for decellularization of allogeneic matrix, whereas it is hard to remove from matrix. Only a small amount of sodium dodecyl sulfate in matrix can cause cytotoxicity.   OBJECTIVE: To provide a high effective method to remove sodium dodecyl sulfate, which residuals in allogeneic matrix. METHODS: The pure water, potassium salt solution and ethanol were chosen to remove sodium dodecyl sulfate. The decellularization degree, residual amount of sodium dodecyl sulfate, composition, structure and tensile properties and cytotoxicity of allogeneic dermis and allogeneic tendon were detected to evaluate the cleaning effect.   RESULTS AND CONCLUSION: In total, ethanol + potassium chloride and 75% ethanol + potassium chloride produced little significant impacts on the component and structure of allogeneic matrix. Firstly, on condition that sodium dodecyl sulfate was infiltrated into allogeneic matrix since DNA amount was controlled under 50 ng/mg (dry weight), the sodium dodecyl sulfate residual results showed a tremendous reduction of 96.7% and 97% in allogeneic dermis and allogeneic tendon, respectively. Secondly, no significant changes occurred in allogeneic dermis and allogeneic tendon for glycosaminoglycan and collagen. Moreover, after carefully washing, the allogeneic tendon exhibited higher the maximum tensile force, strength, and modulus than those after decellularization. Meanwhile, there was no significant difference compared with the raw material. Finally, the cytotoxicity test showed that cell viability was higher than 80% after washing of allogeneic dermis and allogeneic tendon; the cytotoxicity grade was not greater than lever 1. Figures and Tables | References | Related Articles | Metrics

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Biological characteristics of human amniotic mesenchymal stem cells pretreated with different volume fractions of oxygen Tang Jianhong, Zhang Nini, Huang Guilin, Long Yuanzhu, Cui Tianning, Luo Qinliang, Lang Jiachan, Dai Min, Zhang Ligang 2023, 27 (15):  2318-2324.  doi: 10.12307/2023.392 Abstract ( 401 )   PDF (3911KB) ( 40 )   Save BACKGROUND: In recent years, stem cell plays an important role in the repair of tissue injury, among which mesenchymal stem cell transplantation is the most widely used. Mesenchymal stem cells can secrete cytokines through paracrine effect to promote the repair of damaged tissue. Hypoxia pretreatment can improve the biological characteristics of mesenchymal stem cells. Hypoxic preconditioning of human amniotic mesenchymal stem cells may play a better therapeutic role in tissue injury repair.  OBJECTIVE: To study the effects of different hypoxic pretreatment on the proliferation, antiapoptotic ability, and parocrine effect of human amniotic mesenchymal stem cells.   METHODS: The primary human amniotic mesenchymal stem cells were obtained by enzyme digestion method. Passage 3 human amniotic mesenchymal stem cells were pretreated with different hypoxic concentrations for 48 hours and randomly divided into hypoxic pretreatment group (1% O2, 3% O2, 5% O2, and 10% O2) and control group (21% O2). The morphology of human amniotic mesenchymal stem cells was observed under an inverted microscope. The proliferation ability of human amniotic mesenchymal stem cells was detected by CCK-8 assay. Annexin V-FITC/PI kit was used to detect the apoptosis of human amniotic mesenchymal stem cells. The apoptosis gene and hypoxia-inducible factor of human amniotic mesenchymal stem cells were detected by real-time quantitative PCR. The cytokine secretion capacity of human amniotic mesenchymal stem cells in each group was detected by enzyme-linked immunosorbent assay.   RESULTS AND CONCLUSION: Under the microscope, the morphology of human amniotic mesenchymal stem cells in different hypoxic pretreatment groups showed no significant difference. Hypoxic pretreatment could enhance the proliferation, anti-apoptotic and paracrine cytokine capacity of human amniotic mesenchymal stem cells. Pretreatment effect of 1% O2 concentration was better than that of 3% O2, 5% O2, 10% O2 and 21% O2.    Figures and Tables | References | Related Articles | Metrics

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Identification and function of differentially expressed long noncoding RNAs in the chondrogenesis of human adipose-derived mesenchymal stem cells Sun Hong, Deng Jin, Peng Guoxuan, Zhuang Yong, Liu Miao, Ning Xu, Yang Hua 2023, 27 (15):  2325-2332.  doi: 10.12307/2023.370 Abstract ( 436 )   PDF (4112KB) ( 125 )   Save BACKGROUND: The chondrogenic differentiation of human adipose-derived mesenchymal stem cells is affected by many factors. Studies have confirmed that long noncoding RNAs (lncRNAs) play important roles in epigenetic regulation, transcription and post-transcriptional regulation. However, there are few reports on the changes of its expression profile and its regulatory role during the chondrogenic differentiation of human adipose-derived mesenchymal stem cells.   OBJECTIVE: To preliminarily analyze the differentially expressed lncRNAs and their potential functions during the chondrogenesis of human adipose-derived mesenchymal stem cells. METHODS: The human adipose-derived mesenchymal stem cells at 0 day (undifferentiated group) and 14 days (differentiated group) after chondrogenic differentiation were used as research objects. RNA-seq was used to screen lncRNAs and messenger RNAs (mRNAs) with expressed fold change larger than twice between groups. Quantitative real time PCR (qRT-PCR) was used to verify the sequencing results. Bioinformatics analyses including GO function analysis and KEGG pathway analysis were performed for differentially expressed genes to screen adjacent genes and co-expressed genes of lncRNAs.   RESULTS AND CONCLUSION: (1) Compared with the undifferentiated group, a total of 816 lncRNAs and 5 138 mRNAs were significantly differentially expressed in the differentiated group. (2) GO function and KEGG signaling pathway analysis showed that differentially expressed genes were enriched in several biological processes including cellular processes, biological regulation, and metabolic processes, and multiple pathways including focal adhesion kinase, insulin signaling pathway, and Wnt signaling pathway. (3) Analysis results of adjacent genes and co-expressed genes of differentially expressed lncRNAs indicated that some lncRNAs such as SNHG16 and XLOC_003886 might play critical roles in the chondrogenic differentiation of adipose-derived mesenchymal stem cells and cartilage degeneration. (4) These findings suggest that the expression profiles of lncRNAs were significantly altered during the chondrogenesis of adipose-derived mesenchymal stem cells. The biological functions of differentially expressed lncRNAs may be closely related to the functions of adjacent genes and co-expressed genes, thereby regulating the chondrogenic differentiation of adipose-derived mesenchymal stem cells. However, further experiments should be employed to uncover the regulatory roles and underlying molecular mechanisms of differentially expressed lncRNAs. Figures and Tables | References | Related Articles | Metrics

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Transcriptome sequencing analysis of osteogenic rat bone marrow mesenchymal stem cells induced by osteomyelitis Wen Hongjie, Chen Zhong, Yang Huagang, Xu Yongqing 2023, 27 (15):  2333-2338.  doi: 10.12307/2023.387 Abstract ( 285 )   PDF (2696KB) ( 50 )   Save BACKGROUND: Recently, osteomyelitis environment has been found to significantly inhibit the osteogenic differentiation of bone marrow mesenchymal stem cells, thereby affecting bone formation and bone metabolism, but the specific mechanism remains unclear.  OBJECTIVE: Transcriptome analysis was conducted on rat bone marrow mesenchymal stem cells with osteogenic differentiation induced by staphylococcal protein A to search for potential differentially expressed lncRNAs and related regulatory networks.  METHODS: Bone marrow mesenchymal stem cells of rats were divided into experimental group and control group. The former group was induced osteogenic differentiation for 7 and 14 days in staphylococcal protein A (1 μg/mL) (to simulate osteomyelitis environment), while the control group was induced osteogenic differentiation for 7 and 14 days without any treatment. The content detection of alkaline phosphatase and alizarin red staining were used to observe the osteogenic induction of the cells. Two groups of cells were collected for transcriptome sequencing, gene ontology and KEGG bioinformatics analysis. Differential expression levels of lncRNAs were further verified by real-time fluorescence quantitative PCR. RESULTS AND CONCLUSION: (1) After 7 and 14 days of osteogenic differentiation, the staining area of alizarin red in the control group was larger than that in the experimental group, and the alkaline phosphatase activity in the control group was significantly higher than that in the experimental group (P < 0.01). (2) Transcriptome sequencing results found 328 lncRNAs with significant differential expression level, with 184 significantly up-regulated and 144 significantly down-regulated. (3) Gene enrichment analysis showed that the function of differentially expressed genes mainly involved biological process, cell classification and molecular function. KEGG enrichment analysis found that the main signal pathways included tumor necrosis factor, MAPK and intestinal inflammatory disease signaling pathways, which were related to bone formation and bone metabolism. (4) Six differentially expressed lncRNAs related to osteogenesis differentiation were selected, and the expression trends of ENSRNOT00000092811, TCONS_00023877, and XR_001836916.1 were consistent with high-throughput sequencing after qPCR validation. (5) The results showed that multiple lncRNAs were involved in the regulation of osteogenic differentiation ability of rat bone marrow mesenchymal stem cells in osteomyelitis, and they may play a role through signal pathway, such as tumor necrosis factor and MAPK signaling pathways.  Figures and Tables | References | Related Articles | Metrics

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Experimental method of simultaneous culture of primary cortical neurons and astrocytes of Sprague-Dawley suckling rats Ming Jiang, Liao Yidong, Song Wenxue, Mu Deyong, Liu Zongwei, Xu Kaya 2023, 27 (15):  2339-2343.  doi: 10.12307/2023.621 Abstract ( 309 )   PDF (10663KB) ( 50 )   Save BACKGROUND: At present, there are many methods to obtain primary cortical neurons and astrocytes. The traditional method is usually to obtain these two kinds of cells separately, but the experimental method is too cumbersome and wastes experimental materials. It is particularly important to find a simple, economical, and feasible culture method that simultaneously extracts both types of cells.   OBJECTIVE: To observe the effect and precautions of simultaneously extracting neurons and astrocytes from the cerebral cortex of Sprague-Dawley suckling rats. METHODS: The suckling rats within 24 hours of birth were selected and sterilized with 75% alcohol. After the suckling rats were in a coma, they were sacrificed by cutting their spines. The head was severed with scissors along the neck of the suckling rats and placed in a small beaker containing high-glucose DMEM. The skull was opened through the suture and the brain was removed and placed in a petri dish containing high glucose DMEM. The meninges and blood vessels were peeled off on ice, and the brain tissue 2.0-3.0 mm on the surface of the cortex was clipped, digested with papain and DNase, and terminated with DMED/F12 containing 10% fetal bovine serum. Samples were seeded at a density of 1.0×109/L in six-well plates containing slides (treated with polylysine). The morphological changes of neurons were observed under an inverted fluorescence microscope at 1, 3, 5, and 7 days, respectively. Calcien-AM was used for live cell staining to observe cell viability, and β-Tubulin and MAP2 immunofluorescence staining was used to identify neurons. Astrocytes were extracted from the remaining cerebral cortex. After trypsin digestion, filtration, and pipetting, they were inoculated into culture flasks at a suitable concentration. When the cell confluency reached 90%, the astrocytes were shaken on a constant temperature horizontal shaker for 24 hours to purify the astrocytes. After the cells were passaged and purified, they were seeded in six-well plates at 1.0×109/L. Astrocytes were identified by GFAP immunofluorescence staining.  RESULTS AND CONCLUSION: (1) After 1 day of culture, neurons could be seen to adhere to the wall; the cell body increased, and some of the cells grew together, and there were a few synaptic connections between cells. After 3 and 5 days, the cell body further increased, and the synapses were thickened and elongated to form a sparse network. After 7 days, the neurons were obviously aggregated; the synapses grew and thickened, and they connected to each other to form a dense cell network. Calcien-AM live cell staining showed better neuronal viability. The purity of the two identification methods was greater than 90% identified by β-Tubulin and MAP2 immunofluorescence staining. (2) After 3 days of culture, the astrocyte bodies were enlarged, showing spindle and irregular shapes, with a small amount of interconnected cells and many microglia between cells. After 5 days of culture, the cell bodies and protrusions further increased. After 7 days of culture, it was found that the microglia and other impurities between the cells were reduced compared with the previous ones, and the background was relatively clean. The purity of the cells was greater than 95% identified by GFAP immunofluorescence staining. (3) The obtained cortical neurons and astrocytes have good morphology, less impurities and high purity. They can meet the needs of high-purity cortical neurons and astrocytes for neuroscience research. Figures and Tables | References | Related Articles | Metrics

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Primary culture and identification of neurons from cerebral cortex of newborn Sprague-Dawley rats Wang Jing, Lu Sitong, Wu Yinlin, Liu Yudong, Zou Weiyan, Sun Meiqun 2023, 27 (15):  2344-2349.  doi: 10.12307/2023.390 Abstract ( 342 )   PDF (3646KB) ( 41 )   Save BACKGROUND: The quality of cultured neurons is the key to the study of central nervous system diseases, but there has been no unified standard for the methods used. OBJECTIVE: To explore the effects of best selection site and cytarabine treatment conditions on the viability, purity and maturity of primary cultured neurons.  METHODS:  The cells were obtained at 2.0-3.0 mm on the surface of the cerebral cortex of Sprague-Dawley rats within 24 hours of the newborn, and treated with cytarabine at a concentration of 5 μmol/L or 10 μmol/L at 24, 48, and 72 hours after culture. In addition, the whole cerebral cortex was removed for primary culture and treated with cytarabine at a concentration of 5 μmol/L for 48 hours at 48 hours after culture. At 7 days after culture, the morphology of neuron was observed using inverted microscope and the effect of cytarabine on neuronal viability was detected by CCK-8 assay. The purity and maturity of neurons were assessed by immunofluorescence and western blot assay.  RESULTS AND CONCLUSION: (1) Inverted microscope: The density of neurons in the 10 μmol/L cytarabine group at 24, 48, and 72 hours was lower than that in the 5 μmol/L cytarabine group at the same time point, and the neuronal processes in the six groups could be connected to each other to form a dense network structure. The neuron cell body was plump and full of refractive properties. The cell density of the whole cortex group was lower than that of the normal control group, and non-neuronal cells could be clearly observed. (2) CCK-8 assay: The cell viability of each cytarabine group was lower than that of the normal control group (P < 0.001), and the neuronal viability of the 10 μmol/L cytarabine 24-, 48-, and 72-hour groups was lower than that of 5 μmol/L cytarabine group at the same time point (P < 0.05). The neuronal viability in the 5 μmol/L cytarabine 24-hour group was lower than that in the 5 μmol/L cytarabine 48- and 72-hour group (P < 0.01). (3) Immunofluorescence staining: The purity of neurons in each cytarabine group was greater than that in the normal control group and all cortical groups (P < 0.001), and there was no difference in the purity of neurons in each cytarabine group. (4) Western blot assay detection of neuron-specific enolase protein expression: The neuron maturity of each cytarabine group was higher than that of the normal control group (P < 0.05), and the 5 μmol/L cytarabine 48-hour group had the highest maturity. (5) The results showed that the cortex at 2.0-3.0 mm on the surface of the rat cerebral cortex within 24 hours of the newborn treated with 5 μmol/L cytarabine at 48 hours after culture can obtain better neuronal viability, maturity and purity. Figures and Tables | References | Related Articles | Metrics

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Ecto-mesenchymal stem cell-conditioned medium lyophilized powder combined with fibrin glue to repair skin injury in rats Chen Di, Xue Yu, Tang Yu, Fei Xiaoming, Zhuang Qin, Zhou Wenwen, Lyu Demin, Shi Wentao, Zhang Zhijian, Zheng Wenjuan, Jiang Yu 2023, 27 (15):  2350-2355.  doi: 10.12307/2023.386 Abstract ( 298 )   PDF (4043KB) ( 46 )   Save BACKGROUND: Recently, most studies have combined tissue engineering materials with stem cells or factors to improve animal skin injury models. Ecto-mesenchymal stem cells derived from nasal mucosa can be preserved for a long time and has unique advantages in repairing skin damage. OBJECTIVE: To observe the effect of ecto-mesenchymal stem cells-conditioned medium lyophilized powder combined with fibrin glue on the wound healing of skin defects in rats. METHODS: Ecto-mesenchymal stem cells derived from Sprague-Dawley rat nasal mucosa were cultured in vitro, and the conditioned medium from passage 3 was collected and lyophilized. The 30 rat models of skin defects were divided into three groups according to treatment (n=10): the injury control group, received no specific treatment as control; the fibrin glue group, received topical application of fibrin glue; the combination group, received topical application of the fibrin glue contained ecto-mesenchymal stem cells-conditioned medium lyophilized powder. After treatments, the wound healing was observed dynamically and the wound area was measured. The tissue sections of the skin were stained with hematoxylin and eosin and subjected to immunohistochemical staining of cytokeratin-8 and protein-63.  RESULTS AND CONCLUSION: The wound healing rate of the combination group was higher than that of the fibrin glue group and the injury control group (P < 0.001). The staining of tissue sections showed that the epidermis and dermis of the combination group were all regenerated and repaired in 21 days; the regenerated skin in the fibrin glue group was thinner and the skin healing in the injury control group was incomplete. Ecto-mesenchymal stem cells-conditioned medium lyophilized powder in combination with fibrin glue can enhance wound healing of the injured skin in rat models.  Figures and Tables | References | Related Articles | Metrics

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Editing immune-related gene HLA-DRA for the first time by CRISPR/Cas9 technology combined with liposome transfection of endometrial cancer cells with single-plasmid gene knockout method Cai Bo, Li Xiaoxiao, Zhang Linghan, Liu Yanxing, Mao Genhong 2023, 27 (15):  2356-2362.  doi: 10.12307/2023.622 Abstract ( 395 )   PDF (3158KB) ( 75 )   Save BACKGROUND: The abnormal expression of HLA-DR gene is related to the progression and prognosis of various tumors. The research on editing the HLA-DRA gene of endometrial cancer using CRISPR/Cas9 technology has not been reported at home and abroad.   OBJECTIVE: The HLA-DRA gene of HEC-1-A cells was targeted knocked out by CRISPR/Cas9 genome engineering technology, and the function of HLA-DRA was preliminarily explored. METHODS: According to the HLA-DRA gene sequence, sgRNA was designed for HLA-DRA exons, and sg RNA, CRISPR/Cas9, enhanced green fluorescent protein and puromycin were cloned into YKO vector, respectively. The plasmid expressing sgRNA was transfected into HEC-1-A cells by liposome. After evaluating the knockout efficiency of sgRNA according to fluorescence expression, the plasmid expressing sgRNA was transfected and screened with the best concentration of puromycin to obtain stable green fluorescent protein positive cells, which were verified and analyzed by PCR, gene sequencing, and transcriptome sequencing.   RESULTS AND CONCLUSION: After transfection and puromycin screening, HEC-1-A cells stably expressing green fluorescent protein were obtained. Sanger sequencing showed that the HLA-DRA exon gene in HEC-1-A cells was targeted knockout. The transcriptome sequencing results were screened for differential genes. According to the 686 differentially expressed genes screened, GO enrichment analysis and KEGG enrichment analysis were carried out, and the protein interaction network was constructed. Through the analysis of differential genes related to tumor proliferation and differentiation, it was found that the expression of COL3A1, BCL2A1, TACSTD2 and CXCR2 genes was up-regulated, and the expression of GNG11, BMP7, IL1RN, PLEK2 and CDH6 genes was down regulated. It is concluded that the HLA-DRA gene is involved in the functional regulation of a variety of organs, tissues, and cells. In addition, HLA-DRA genes may regulate the proliferation, differentiation, migration, and invasion of endometrial adenocarcinoma cells through two pathways (upregulation/downregulation). To establish a single plasmid gene knockout method using CRISPR/Cas9 technology combined with liposome transfection, HLA-DRA was knocked out for the first time, which laid the experimental foundation for the study of endometrial cancer immunotherapy. Figures and Tables | References | Related Articles | Metrics

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Effects of neural stem cell transplantation in different ways on neuroinflammation in amyotrophic lateral sclerosis Lin Yanchen, Li Jingjing, Lu Guangxu, Dai Erqing, Chen Jing, Zhong Shijiang 2023, 27 (15):  2363-2370.  doi: 10.12307/2023.371 Abstract ( 418 )   PDF (3792KB) ( 108 )   Save BACKGROUND: Neuroinflammation affects the progression of amyotrophic lateral sclerosis. In vitro studies have shown that neural stem cells have anti-inflammatory effect, but whether they can be anti-inflammatory in amyotrophic lateral sclerosis mouse, and the mechanism and optimal transplantation route are still unclear.   OBJECTIVE: To investigate the anti-inflammatory effect and mechanism of neural stem cell transplantation in different ways on amyotrophic lateral sclerosis model G93A-SOD1 mice. METHODS: Neural stem cells were isolated and identified, transfected with green fluorescent protein. Totally 78 G93A-SOD1 mice aged 70 days were divided into lateral ventricle group, tail vein group, and control group. After adaptive feeding, 5×105 green fluorescent protein-transfected neural stem cells were transplanted into the lateral ventricle, and 1×106 green fluorescent protein-transfected neural stem cells were injected through the tail vein at the age of 84 days. From the age of 85 days, modified Wrathall motor score and rotation test were performed every week to evaluate motor function. Onset time, disease duration and survival time were recorded. At the age of 105 days, immunofluorescence method was conducted to detect survival, migration and differentiation of neural stem cells transfected with green fluorescent protein. The number of motor neurons was measured by Nissl staining. The expression of ChAT was detected by western blot assay. Immunofluorescence was used to detect the expression of NeuN in spinal cord anterior horn motor neurons. The protein and mRNA levels of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6 and transforming growth factor beta in cerebrospinal fluid were detected by ELISA and RT-PCT. Western blot assay was used to detect the expression of iNOS, CD206 and NF-κB pathway proteins in the spinal cord. The pathological changes of gastrocnemius muscle were detected by hematoxylin-eosin staining.   RESULTS AND CONCLUSION: (1) The extracted neural stem cells grew and differentiated well and could be transfected by green fluorescent protein. (2) The lateral ventricle pathway was more favorable for neural stem cells to enter the central nervous system in the super-early stage after the onset of disease, and decreased the levels of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, increased the level of tumor necrosis factor-β, reduced the expression of inducible nitric oxide synthase and increased the expression level of CD206, inhibited the activation of NF-κB pathway, slowed down the progression of motor function damage, and reduced the degree of pathological damage of skeletal muscle. (3) In the super-early stage after the onset of the disease, the effects of two ways of transplanting neural stem cells to protect the anterior horn motor neurons and prolong the course of disease and survival time of mice were limited. (4) Results show that in the super early stage after the onset of amyotrophic lateral sclerosis, the lateral ventricle may be a better way of transplanting neural stem cells, which has a good anti-inflammatory effect. The mechanism may be regulating the polarization direction of microglia and inhibiting the activation of NF-κB pathway. Figures and Tables | References | Related Articles | Metrics

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Eucommia ulmoides Oliver aqueous extract promotes bone marrow mesenchymal stem cell proliferation and osteoblastic differentiation through upregulating Nur77 protein expression He Zike, Wang Shangzeng 2023, 27 (15):  2371-2378.  doi: 10.12307/2023.382 Abstract ( 390 )   PDF (2595KB) ( 187 )   Save BACKGROUND: Bone marrow mesenchymal stem cells are precursor cells of osteoblasts. Exploring its differentiation mechanism is of great significance for guiding the prevention and treatment of osteoporosis. Eucommia ulmoides Oliver can induce the osteogenic differentiation of bone marrow mesenchymal stem cells. However, it is unclear about the effects of Eucommia ulmoides Oliver on proliferation and differentiation of bone marrow mesenchymal stem cells and Nur77/MDM2/p53 pathway.   OBJECTIVE: To investigate the effect and mechanism of Eucommia ulmoides Oliver aqueous extract on bone marrow mesenchymal stem cell proliferation and differentiation. METHODS: The aqueous extract from Eucommia ulmoides Oliver bark was used to treat human and mouse bone marrow mesenchymal stem cells. The CCK-8 assay and Annexin V-FITC/PI assay were used to detect the proliferation and apoptosis of bone marrow mesenchymal stem cells. The expression of proliferation and apoptosis related proteins and the expression of Nur77 and its downstream MDM2, p53 pathway related proteins and the ubiquitination of p53 protein were detected by western blot assay. After directed induction of adipogenic and osteogenic differentiation, the degree of differentiation was evaluated by detecting the expression of adipocytes and osteoblasts marker proteins using western blot assay. Nur77 small interfering RNA (siRNA) was transfected into bone marrow mesenchymal stem cells treated with 10 mg/mL Eucommia ulmoides Oliver aqueous extract. Cell proliferation, apoptosis and differentiation were detected. Finally, after knocking down Nur77, bone marrow mesenchymal stem cells were treated with p53 inhibitor (Pifithrin-α), and the changes of cell proliferation, apoptosis and differentiation were detected to clarify the mechanism.   RESULTS AND CONCLUSION: (1) The Eucommia ulmoides Oliver aqueous extract promoted the proliferation and osteoblastic differentiation of bone marrow mesenchymal stem cells, inhibited cell apoptosis and adipogenic differentiation. (2) Eucommia ulmoides Oliver aqueous extract upregulated Nur77 and MDM2 protein expression and promoted p53 ubiquitination. Knockdown of Nur77 inhibited MDM2 protein expression and p53 protein ubiquitination, promoted p53 protein expression, and further inhibited bone marrow mesenchymal stem cell proliferation and osteogenic differentiation. (3) Pifithrin-α reversed the effects of Nur77 siRNA, promoted bone marrow mesenchymal stem cell proliferation and osteoblastic differentiation, and inhibited cell apoptosis and adipogenic differentiation. (4) It is concluded that the Eucommia ulmoides Oliver aqueous extract promotes bone marrow mesenchymal stem cell proliferation and osteoblastic differentiation via the Nur77/MDM2/p53 pathway, which provides a theoretical reference for the research of Eucommia ulmoides Oliver in bone-related disease. Figures and Tables | References | Related Articles | Metrics

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Cell co-culture system of dental pulp regenerative tissue engineering Zhang Chuhan, Zhang Dongmin, Xu Wenan 2023, 27 (15):  2379-2384.  doi: 10.12307/2023.376 Abstract ( 556 )   PDF (1782KB) ( 44 )   Save BACKGROUND: By removing all pulp tissue from the tooth, conventional root canal therapy will cause teeth to lose their physiological function and ability to regenerate tissue. The cultivation of dental pulp stem cells in vitro, the formation of dental pulp-like tissue, and the transplantation of this tissue into the pulp cavity have become an ideal method of dental pulp regeneration.   OBJECTIVE: To summarize research progress on forming dental pulp-like tissue from dental pulp stem cells via a co-culture system, as well as provide ideas for stem cell therapy for dental pulp tissue regeneration. METHODS: The first author searched PubMed, CNKI, and Wanfang databases for relevant literature published before May 2022. The English search terms were “dental pulp regeneration, dental pulp stem cell, co-culture, tissue engineering, signaling pathway”, and the Chinese search terms were “dental pulp regeneration, dental pulp stem cells, co-culture, tissue engineering, scaffold, signaling pathway”. Totally 67 articles meeting the criteria were summarized and described.   RESULTS AND CONCLUSION: (1) Different combinations of cells are used in co-culture systems to form the main body of the cell and the combined body. (2) Direct co-culture and indirect co-culture are the two types of combination modes at present. Through the intervention of biological scaffold materials and a change in culture conditions, the co-culture outcome can be divided into two-dimensional regenerated tissues and three-dimensional regenerated tissues. (3) Direct co-culture creates an extracellular matrix and microenvironment that facilitates stem cell proliferation and differentiation through intercellular contact. (4) Indirect co-culture addresses the problem of insufficient sources of combined cells and immune rejection between individuals. The biological factors produced by the combined cells can be more easily made into clinical drugs and biological scaffold materials. (5) Though the co-culture system has superior performance in angiogenesis, there are few reports on other structures, and the regeneration of tissue from the co-culture outcome is uncertain. Furthermore, there are limitations to applying newly generated tissue generated by the co-culture system to clinical practice due to tooth anatomical constraints and rejection mechanisms. Figures and Tables | References | Related Articles | Metrics

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Action mechanism of traditional Chinese medicine to regulate neural stem cells in treatment of Alzheimer’s disease Ying Chunmiao, Ma Yucheng, Fan Feiyan, Gao Chen, Wang Shaona, Yang Xing, Zhang Yunke 2023, 27 (15):  2385-2394.  doi: 10.12307/2023.361 Abstract ( 416 )   PDF (1713KB) ( 220 )   Save BACKGROUND: Neural stem cells have the effect of repairing, replacing damaged nerve cells, stimulating neurogenesis, rebuilding cell circuits, inhibiting apoptosis, and have shown a good therapeutic effect in the study of Alzheimer’s disease. Traditional Chinese medicine also has significant efficacy on regulating the proliferation and differentiation of neural stem cells and improving nerve cell viability and cell survival.   OBJECTIVE: To review the mechanism of traditional Chinese medicine regulating neural stem cells in the treatment of Alzheimer’s disease, so as to provide a reference for the research and treatment of new drugs for Alzheimer’s disease. METHODS: The articles on Wanfang, CNKI, PubMed, Web of Science and other databases about neural stem cell regulated by traditional Chinese medicine in the treatment of Alzheimer’s disease from 2010 to 2022 were searched, with “neural stem cells, traditional Chinese medicine, Alzheimer’s disease” as the key words in Chinese and English. The outdated and repetitive viewpoints were excluded, and the retrieved articles were analyzed and sorted out, and a total of 121 articles were included for analysis.   RESULTS AND CONCLUSION: (1) The definition and pathogenesis of neural stem cells and Alzheimer’s disease were sorted out. (2) The mechanism of action of traditional Chinese medicine in regulating neural stem cells in the treatment of Alzheimer’s disease was summarized, mainly including promoting the proliferation of neural stem cells, improving the microenvironment in the brain, inhibiting the apoptosis of nerve cells, inducing neural stem cell differentiation into neurons, improving neuroinflammation, and regulating vascular nerve units. (3) Through the existing research, the relevant factors and signaling pathways of traditional Chinese medicine to regulate neural stem cells in the treatment of Alzheimer’s disease were summarized, such as Nestin protein, microtubule-associated protein, cerebrogenic neurotrophic factor, vascular endothelial growth factor and Notch signal pathway, P13k/Akt signaling pathway, brain-derived neurotrophic factor/TrkB signaling pathway, and Wnt/β-catenin signaling pathway. It may provide a relevant reference for the future research on new drugs for Alzheimer’s disease and new clinical treatment methods. Figures and Tables | References | Related Articles | Metrics

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Role of macrophage migration inhibitory factor for stem cells Zheng Xiaohan, Wei Yanzhao, Huang Ting, Wei Xufang, Sun Shengtong, Wang Tan, Zhao Zhenqiang 2023, 27 (15):  2395-2403.  doi: 10.12307/2023.355 Abstract ( 398 )   PDF (1720KB) ( 67 )   Save BACKGROUND: Stem cells are self-renewing cells with differentiation potential and stem cell therapy is a promising therapeutic approach. Macrophage migration inhibitory factor is expressed in almost all mammalian cells and is essential for many physiological processes. Current studies have demonstrated that macrophage migration inhibitory factor is expressed on a variety of stem cells and regulates the proliferation, differentiation and migration of many stem cells.   OBJECTIVE: To describe the basic characteristics of macrophage migration inhibitory factor and to elaborate on the role and mechanism of macrophage migration inhibitory factor on stem cells. METHODS: PubMed and CNKI databases were searched for relevant articles published in the past ten years. The key words were “macrophage migration inhibitory factor, cancer stem cell, embryonic stem cell, neural stem cell, mesenchymal stem cell, endothelial progenitor cell, stem cell therapy, tissue engineering” in Chinese and English, respectively. After removal of poorly related, outdated, and duplicate studies by reading the title and abstract, 85 articles were finally included in result analysis.   RESULTS AND CONCLUSION: (1) Macrophage migration inhibitory factor protein consists of three subunits that interact on the cell surface by interacting with receptors CD74, CD44, CXCR2, CXCR4 and CXCR7. Macrophage migration inhibitory factor is stored intracellularly and secreted through non-classical pathways, and a variety of factors can affect macrophage migration inhibitory factor expression as well as secretion. (2) Macrophage migration inhibitory factor promotes migration, invasion, metastasis, escape and tumorigenicity of tumor stem cells through different signaling pathways. (3) Currently, it is relatively clear that macrophage migration inhibitory factor promotes neural differentiation of mouse embryonic stem cells. (4) Macrophage migration inhibitory factor promotes the proliferation and survival of neural stem cells through multiple signaling pathways. (5) Macrophage migration inhibitory factor acts on mesenchymal stem cells to inhibit apoptosis, promote survival, delay senescence, and increase paracrine effects of mesenchymal stem cells. In addition, macrophage migration inhibitory factor has also been shown to inhibit mesenchymal stem cell homing by binding to the receptor CD74. (6) Several studies have demonstrated that macrophage migration inhibitory factor activates downstream signaling pathways through CXCR4 receptors to promote endothelial cell migration and revascularization. (7) Macrophage migration inhibitory factor acts on tumor stem cells, embryonic stem cells, neural stem cells, mesenchymal stem cells, and endothelial progenitor cells to affect their proliferation, differentiation, migration, and apoptosis processes. Some of these effects are still controversial, and the exact mechanisms need to be further verified.   Figures and Tables | References | Related Articles | Metrics

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Feasibility and advantages of mesenchymal stem cells for repairing Achilles tendon injury Li Wei, Lin Meina, Lu Yongping, Sui Yu, Jiang Miao 2023, 27 (15):  2404-2411.  doi: 10.12307/2023.362 Abstract ( 420 )   PDF (1758KB) ( 106 )   Save BACKGROUND: The Achilles tendon is a common site of injury in sports, especially in excessive or improper sports, which is more likely to be affected and difficult to recover after injury. To find a safe, effective, and rapid repair method is always the direction of clinical treatment of Achilles tendon injury, but the effect is not ideal. In recent years, due to the strong repair potential, mesenchymal stem cells have been tried to be used in the treatment of a variety of diseases, and some studies have applied mesenchymal stem cells to repair Achilles tendon injury, with good results.   OBJECTIVE: To review the application of mesenchymal stem cells derived from bone marrow, adipose tissue, and tendon in the treatment of Achilles tendon injury, and explore the feasibility and advantages of mesenchymal stem cells in the treatment of Achilles tendon injury, providing a new idea for the treatment of Achilles tendon injury. METHODS: The articles included in CNKI database, Wanfang database, Baidu Academic Database, Web of Science database, PubMed database and Google Academic Database were searched by computer. The Chinese and English search terms were “Achilles tendon, Achilles tendon injury, Achilles tendon rupture, stem cells, mesenchymal stem cells, MSCs, biological materials, tissue engineering”. The screened articles were sorted out and summarized, and those that did not meet the inclusion criteria were excluded. Finally, 101 articles were selected for review.   RESULTS AND CONCLUSION: The application of mesenchymal stem cells from different tissues independently or in combination with biomaterials is beneficial for tendon injury repair, but the specific mechanisms involved are not clear, which may include the differentiation of mesenchymal stem cells into tendon cells, regulation of growth factor release and tendon related gene expression. Finding the most suitable seed cells and biomaterials for the treatment of Achilles tendon injury is the key to tissue engineering repair of Achilles tendon. Figures and Tables | References | Related Articles | Metrics

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Differentiation of bone marrow mesenchymal stem cells into meniscus fibrochondrocytes induced by transforming growth factor beta Yang Jun, Li Peng 2023, 27 (15):  2412-2419.  doi: 10.12307/2023.609 Abstract ( 290 )   PDF (1651KB) ( 78 )   Save BACKGROUND: Bone marrow mesenchymal stem cells can be induced to differentiate into fibrochondrocytes as seed cells in tissue engineering, and the application of cytokines transforming growth factor beta 1 (TGF-β1) and transforming growth factor beta 3 (TGF-β3) in inducing differentiation is still a research hotspot at present.   OBJECTIVE: To review the literature on the differentiation of bone marrow mesenchymal stem cells into chondrocytes induced by TGF-β1 and TGF-β3, and provide a theoretical basis for further guiding the differentiation of bone marrow mesenchymal stem cells into fibrochondrocytes, as well as a new strategy for the treatment of meniscus injury and degeneration in clinic in the future.   METHODS: Retrieval of PubMed database, CNKI database and Wanfang database from January 1990 to March 2022 was performed. The Chinese and English key words were “transforming growth factor beta 1; transforming growth factor beta 3; bone marrow mesenchymal stem cells; meniscus; fibrochondrocyte”. According to the screening criteria, 78 articles were finally included and reviewed.  RESULTS AND CONCLUSION: (1) TGF-β is mainly divided into TGF-β1, TGF-β2 and TGF-β3 subtypes, among which the most studied cytokines are TGF-β1 and TGF-β3. (2) TGF-β induces the differentiation of bone marrow mesenchymal stem cells into chondrocytes by activating SOX9 transcription factors in the nucleus mainly through TGF-β/Smad signaling pathway. (3) TGF-β1 can induce the differentiation of bone marrow mesenchymal stem cells into hyalchondrocytes. With the extension of culture time, hyalchondrocytes can undergo dedifferentiation and become fibrochondrocytes. (4) TGF-β3 mainly induces the differentiation of bone marrow mesenchymal stem cells into fibrochondrocytes and promotes the synthesis and secretion of type I collagen and proteoglycan. (5) At present, the treatment of meniscus injury and degeneration is not ideal, and the emergence of tissue engineering provides a new strategy for its treatment. The specific method is to implant seed cells into the meniscus injury site, which can restore the meniscus function and regenerate fibrocartilage tissue. However, the experiment is still in vitro and animal model stage, and its clinical treatment and availability for meniscus injury still need to be explored in a large number of subsequent experiments. Figures and Tables | References | Related Articles | Metrics

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Mechanism and effect of platelet-rich plasma-derived exosomes for treating knee osteoarthritis Huang Shuangshuang, Xiang Xiaona, Yu Xi, He Jing 2023, 27 (15):  2420-2426.  doi: 10.12307/2023.383 Abstract ( 485 )   PDF (1776KB) ( 114 )   Save BACKGROUND: Osteoarthritis is a common degenerative joint disease. Regenerative therapy has always been a research hotspot for the repair of cartilage in knee osteoarthritis, and platelet-rich plasma-derived exosomes may serve as a new regenerative treatment modality.   OBJECTIVE: To review the current literature and summarize the application, role and potential mechanism of platelet-rich plasma-derived exosomes in knee osteoarthritis. METHODS: Chinese and English keywords were “platelet-rich plasma, extracellular vesicles, exosomes, knee osteoarthritis”. Embase, Medline, Cochrane Central Register of Controlled Trials, PubMed, Wanfang, and CNKI were retrieved. 1 007 articles were preliminarily obtained. A total of 65 articles were selected for review according to the inclusion and exclusion criteria.   RESULTS AND CONCLUSION: (1) The preparation of platelet-rich plasma-derived exosomes involves the preparation, activation, and acquisition of exosomes by kits or ultra-high-speed centrifugation methods, and the identification methods include marker expression detection, morphological observation, and nanoparticle tracking analysis. (2) The role of platelet-rich plasma-derived exosomes include improving their proliferation by inhibiting chondrocyte apoptosis, promoting chondrocyte migration, inhibiting the secretion of inflammatory factors, and promoting extracellular matrix synthesis and secretion. (3) In terms of mechanism, PI3K/Akt, Erk1/2, Akt/Bad/Bcl-2 and Wnt/β-catenin signaling pathways are involved. Figures and Tables | References | Related Articles | Metrics

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Application status and prospect of menstrual blood-derived stem cells and their exosomes Ma Yujiu, Zhang Xudong, Tan Jichun 2023, 27 (15):  2427-2434.  doi: 10.12307/2023.607 Abstract ( 513 )   PDF (1637KB) ( 75 )   Save BACKGROUND: Menstrual blood-derived stem cells are derived from female menstrual blood. Mesenchymal stem cells with multidirectional differentiation potential are easily accessible, weakly immunogenic, highly proliferative, stable passage, and free from ethical controversy. Exosomes derived from menstrual blood-derived stem cells have the same efficacy as menstrual blood-derived stem cells in tissue regeneration and injury recovery. Menstrual blood-derived stem cells and their exosomes have yielded exciting results in preclinical and clinical studies for the treatment of various diseases.   OBJECTIVE: To review the progress of basic research and clinical applications related to menstrual blood-derived stem cells and their exosomes, as well as the potential future applications and issues to be considered. METHODS: A computerized search of PubMed and the CNKI database from 2000 to 2022 for literature related to menstrual blood-derived stem cells and menstrual blood-derived stem cell exosomes was conducted. Finally, 75 articles were selected for review analysis.   RESULTS AND CONCLUSION: (1) Menstrual blood-derived stem cells are mesenchymal stem cells with multidirectional differentiation function, characterized by abundant source, weak immunogenicity and high proliferative capacity. (2) The exosomes are the main mediators of the paracrine function of menstrual blood-derived stem cells and have the same efficacy as the source cells in promoting tissue regeneration and injury repair. Both have the ability to be anti-inflammatory, anti-apoptotic and promote tissue and organ function recovery, and have demonstrated more excellent therapeutic levels in animal test models of various systemic diseases, where menstrual blood-derived stem cells have been used in clinical patients in diseases such as uterine adhesions, congestive heart failure, multiple sclerosis and viral pneumonia, and have greatly delayed the disease progression without producing side effects such as tumor or allergic reactions. (3) However, only 15 years have passed since the discovery of menstrual blood-derived stem cells in 2007. Therefore, menstrual blood-derived stem cells and their exosomes have the shortcomings of insufficient samples and short years of application. Long-term preclinical trials are still needed to verify their safety and efficacy. In addition, to be truly applied in clinical practice, it is also necessary to find a more standardized way of administration, so it is necessary to issue relevant application guidelines in the future. (4) The combination of menstrual blood-derived stem cells and their exosomes with 3D scaffold technology has been used in animal trials for pelvic organ prolapse, skin damage due to diabetes, osteochondral defects, and bladder wall reconstruction. More clinical applications can be developed in the future by combining various advantages of menstrual blood-derived stem cells and their exosomes with tissue engineering and material science to gradually carry out clinical research. Figures and Tables | References | Related Articles | Metrics

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Mesenchymal stem cell-derived exosome transplantation for ischemic heart disease Liu Dongyue, Wang Xianyun, Wang Le, Zheng Mingqi, Yin Yajuan, Yang Jiawei, Ding Lini, Liu Gang 2023, 27 (15):  2435-2442.  doi: 10.12307/2023.612 Abstract ( 435 )   PDF (2616KB) ( 79 )   Save BACKGROUND: Ischemic heart disease is one type of disease that seriously threatens human life and health. Mesenchymal stem cells derived exosomes have shown obvious therapeutic effects and application prospects in ischemic heart disease, and make important research progress.   OBJECTIVE: To review the therapeutic effect of mesenchymal stem cells derived exosomes for ischemic heart disease, repair mechanisms, optimized plan and improved transplantation strategy. METHODS: The relevant articles published from January 1973 to March 2022 were searched in PubMed by the first author in February 2021. The English key words were “mesenchymal stem cell, exosome, ischemic heart disease”. Finally, 88 articles were included and analyzed.   RESULTS AND CONCLUSION: (1) Exosomes secreted by stem cells are one of the most important components of stem cell excretion to play functional regulation which have shown obvious therapeutic effects and application prospects in ischemic heart disease. (2) Mesenchymal stem cells derived exosomes can promote the angiogenesis and protect ischemia-injured myocardial tissue, inhibit cardiac fibrosis and improve immune regulation, finally promote myocardial repair and the improvement of cardiac function. (3) The production or functional properties of mesenchymal stem cells derived exosomes can be optimized by genetic engineering modification, miRNA modification, pretreated of drugs or physical intervention, and improve exosome production, so as to improve their therapeutic effect on ischemic heart disease. (4) Using biomaterials to carry exosomes, two-step delivery method, exosome spray technology or cell membrane modified exosomes and other exosome transplantation optimization strategies can effectively improve the retention rate of mesenchymal stem cell-derived exosomes in injured myocardial tissue, thereby enhancing their therapeutic effect on ischemic heart disease. Figures and Tables | References | Related Articles | Metrics

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Application and role of exosome-regulated ferroptosis in disease diagnosis and treatment Nong Fuxiang, Jiang Zhixiong, Li Yinghao, Xu Wencong, Shi Zhilan, Luo Hui, Zhang Qinglang, Zhong Shuang, Tang Meiwen 2023, 27 (15):  2443-2452.  doi: 10.12307/2023.608 Abstract ( 217 )   PDF (2267KB) ( 43 )   Save BACKGROUND: At present, studies have been done to reveal the relationship between exosomes and ferroptosis, but the research is still limited. Therefore, further exploration of the relationship between exosomes and ferroptosis will help to seek new treatment strategies and reliable basis for clinical treatment of diseases.   OBJECTIVE: To expound the biological characteristics of exosomes, the mechanism of ferroptosis, and the main ways of exosomes regulating ferroptosis, and summarize the application progress of exosomes inducing or inhibiting ferroptosis in the fields of tumor, cardiovascular system, nervous system disease and liver disease. METHODS: Relevant articles were retrieved in CNKI and PubMed using computer. Search terms included “exosomes, ferroptosis, disease” in Chinese and English. Finally, 66 articles related to the research purpose of the article were included for further review.  RESULTS AND CONCLUSION: (1) Exosomes play a regulatory role in promoting cell ferroptosis by participating in iron metabolism, lipid metabolism and amino acid metabolism. (2) Exosomes play an important role in the treatment of various diseases by inducing or inhibiting ferroptosis: on the one hand, exosomes induce ferroptosis of cancer cells, inhibit tumor growth and metastasis, and improve the effect of tumor targeted therapy. On the other hand, by inhibiting ferroptosis, exosomes promote the regeneration and repair of myocardial ischemia-reperfusion and reduce cardiac toxicity in cardiovascular disease. In terms of nervous system diseases, it has played a role in inhibiting cerebral hemorrhage and reducing sepsis. In liver diseases, it can improve hepatic ischemia-reperfusion. (3) Although the specific mechanism by which exosomes regulate ferroptosis in various diseases has not been fully explored, and the relevant research is still in the preliminary stage. However, the regulation of ferroptosis by exosomes is expected to become one of the new potential targets for clinical treatment of various diseases in the future. Figures and Tables | References | Related Articles | Metrics

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Role of exosomes and miRNAs in the mechanism, diagnosis and treatment of premature ovarian insufficiency Li Ran, Jia Hongling, Zhang Chunxiao, Zhao Ruoxi, Dong Jingwen, Cheng Yixin, Cui Wenzhe, Zhang Jing 2023, 27 (15):  2453-2460.  doi: 10.12307/2023.614 Abstract ( 413 )   PDF (1863KB) ( 115 )   Save BACKGROUND: Premature ovarian insufficiency is one of the important causes affecting female reproductive health in clinical practice. In recent years, with the development of regenerative medicine, many scholars believe that mesenchymal stem cells improve ovarian mesenchymal microenvironment and promote ovarian tissue repair by secreting related cytokines (such as exosomes and miRNA) through paracrine pathway.   OBJECTIVE: To summarize and analyze the research progress of exosomes and miRNA in the treatment of premature ovarian insufficiency, explore the related mechanism, and provide theoretical basis for further research and clinical diagnosis and treatment of exosomes and miRNA in the treatment of early-onset ovarian insufficiency. METHODS: The articles from the establishment of the database to June 2022 were searched in CNKI database and PubMed database. The Chinese search words were “exosomes, miRNA, premature ovarian insufficiency, premature ovarian failure”, and the English search words were “exosome, miRNA, ovary, premature ovarian failure, premature ovarian insufficiency”. Articles whose purposes were irrelevant to the review and repeated were excluded. The retrieved articles on mechanism and diagnosis and treatment were sorted out. A total of 63 articles were included for analysis.   RESULTS AND CONCLUSION: (1) All kinds of exosomes and miRNAs have good therapeutic effects on cells and animal models of premature ovarian insufficiency, and the specific mechanisms include promoting proliferation, affecting apoptosis, secretion of hormones, oxidative stress and inflammatory response. (2) A large number of preclinical experiments have provided theoretical basis for clinical diagnosis and treatment, but clinical trials are still in their infancy, and their safety and efficacy need to be further confirmed. Exosomes play an important role in the process of acupuncture therapy. Exosomes are used as a breakthrough point to intervene the mechanism of targeted acupuncture therapy, so as to further improve the therapeutic effect of acupuncture. (3) From the summary, we can see that the therapeutic effect of exosomes and miRNA on premature ovarian insufficiency is not only limited to a certain aspect, but also achieves good therapeutic effect through the synergistic interaction of multiple pathways and multiple targets. Figures and Tables | References | Related Articles | Metrics