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    08 May 2020, Volume 24 Issue 13 Previous Issue    Next Issue
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    Matched-sibling donor versus unrelated umbilical cord blood transplantation for treating hematological malignancies in children
    Qin Yang, Wan Dingming, Cao Weijie, Zhang Suping, Li Li, Zhang Ran, Song Yongping, Zhang Yanli, Wang Dao
    2020, 24 (13):  1969-1975.  doi: 10.3969/j.issn.2095-4344.2062
    Abstract ( 447 )   PDF (758KB) ( 123 )   Save

    BACKGROUND: In recent years, umbilical cord blood has gradually become a crucial alternative source of stem cells for related and unrelated bone marrow or peripheral blood hematopoietic stem cell transplantation, which is increasingly used in the treatment of hematological malignancies in children.

    OBJECTIVE: To compare the clinical efficacy of sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation for treating hematological malignancies in children.

    METHODS: The clinical data of children with hematological malignancies who received umbilical cord blood transplantation at the Hematopoietic Stem Cell Transplantation Center of the First Affiliated Hospital of Zhengzhou University between January 1, 1998 and December 31, 2018 was retrospectively analyzed. All the patients received myelablative conditioning regimen, and cyslosporine A combined with or without mycophenolate mofetil were concurrently adopted for graft-versus-host disease prophylaxis.

    RESULTS AND CONCLUSION: (1) Two patients in the sibling donor umbilical cord blood transplantation group and three in the unrelated umbilical cord blood transplantation group did not attain hematological engraftment and subsequently died from infection, and other patients succeeded in hematological engraftment. The median time of neutrophil and platelet engraftment in the sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups was [17 days (11-43 days), 18 days (12-45 days), P=0.307] and [20.5 days (15-50 days), 27 days (18-56 days), P=0.773]. There was no significant difference between the two groups. (2) The incidence of acute graft-versus-host disease and chronic graft-versus-host disease in the sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups was 36% vs. 43% (P=0.737) and 15% vs. 33% (P=0.412). There was no significant difference between the two groups. There was also no significant difference in the incidence of infection after transplantation between sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups (56% vs. 71%, P=0.343). (3) There were no significant differences in the 2-year overall survival (61% vs. 36%, P=0.301), or 2-year relapse-free survival (56% vs. 33%, P=0.151). The 5-year overall survival and 5-year relapse-free survival in the sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups were 54% vs. 24% (P=0.044) and 50% vs. 20% (P=0.039). The results showed that there was a significant difference in long-term survival rate between two groups. (4) Our results reveal that both sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation are safe, effective and applicable for children with hematological malignancies. In particular, there are significant benefits in the long-term survival of substitute donor transplantation for pediatric patients with hematological malignancies. 

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    Separation of adipose-derived stromal vascular fraction cells by a variety of physical methods: a comparative study
    Lu Peiling, Feng Chunchao, Liang Miaomiao, Wei Jiatian, Huang Jing, Cai Haiming, Wu Guohui, Zhang Linghua, Nie Yunfei
    2020, 24 (13):  1976-1982.  doi: 10.3969/j.issn.2095-4344.2045
    Abstract ( 453 )   PDF (719KB) ( 61 )   Save

    BACKGROUND: Increasing attention has been paid to vascular components of the adipose-derived matrix and adipose-derived stem cells in tissue engineering. Existing methods for separating the vascular components of the adipose-derived matrix mainly include enzymatic and bolus injection, both of which have fatal disadvantages. 

    OBJECTIVE: To search for a method for preparing adipose-derived stromal vascular fractions with high efficiency, safety, and simplicity.

    METHODS: The group without any treatment was used as the negative control, and the enzymatic hydrolysis method served as the positive control. The enzymatic hydrolysis method, traditional bolus method, modified bolus method, glass beads method and built-in ultrasonic waves method were compared through cell volume, survival rate, cell fragments, cell viability, increment rate and detection of microbial infection. The enzymatic hydrolysis method and the common bolus injection method were commonly used in the separation of vascular component cells of the fat source matrix; the improved bolus method was a method obtained by improving on the basis of the ordinary bolus method; the glass bead method was to use the glass bead to oscillate. The shear force generated was obtained by adding glass beads to the fat granules and shaking at 2 500 r/min for 9 minutes to prepare stromal vascular fraction cells. Using the built-in ultrasonic method, adipose tissue was treated at 25 W for 36 seconds to obtain stromal vascular fraction cells through a cavitation effect. 

    RESULTS AND CONCLUSION: (1) The size of stromal vascular fraction cells isolated by five methods showed no significant difference (P > 0.05). (2)The cell viability was lowest in the negative control group, and highest in the enzymatic hydrolysis group. The cell viability in the enzymatic hydrolysis, glass bead, and built-in ultrasonic wave groups was significantly higher than that in the modified and traditional bolus groups (P < 0.05). (3) The cell survival rate and cell proliferation rate in the enzymatic hydrolysis, glass bead, and built-in ultrasonic wave groups were significantly higher than those in the modified and traditional bolus groups (P < 0.05). (4) The cell fragmentation rate and cell apoptosis rate in the enzymatic hydrolysis, glass bead, and built-in ultrasonic wave groups were significantly lower than those in the modified and traditional bolus groups (P < 0.05). (5) These results indicate that the built-in ultrasonic method and the glass bead method are better in enriching vascular components of the adipose-derived matrix. But glass bead method adds exogenous products, so it increases the risk of pollution. Built-in ultrasonic method inserts the ultrasound probe into the adipose tissue, but as long as the ultrasound probe is thoroughly sterilized, the risk of contamination is minimized. In general, the built-in ultrasonic method and the glass bead method are superior to modified and traditional bolus methods.

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    Guishen Pill water extract intervenes with the proliferation of bone marrow mesenchymal stem cells and expression levels of PI3K and AKT in Sprague-Dawley rats
    Liu Yan, Guan Yongge, Song Yang
    2020, 24 (13):  1983-1988.  doi: 10.3969/j.issn.2095-4344.2051
    Abstract ( 374 )   PDF (761KB) ( 52 )   Save

    BACKGROUND: The effect of kidney-tonifying prescriptions on proliferation of bone marrow mesenchymal stem cells has been verified, but its mechanism of action is still unclear. In this study, we took Guishen Pil as an example to explore its functional mechanism.

    OBJECTIVE: To explore the relationship between Guishen Pill nourishing kidney essence and proliferation of bone marrow mesenchymal stem cells by observing the effect of Guishen Pill water extract on the proliferation of bone marrow mesenchymal stem cells.

    METHODS: Bone marrow mesenchymal stem cells were isolated from the femoral bone marrow of 3-week-old male Sprague-Dawley rats and cultured in vitro. The cells were purified using the whole bone marrow adherence method, and the passage 3 cells of higher purity were selected for the drug intervention. The cells were divided into blank control group and 10, 20, 40, 80 and 100 mg/L Guishen Pill groups. The dose-effect and time-effect relationships were investigated after cultured for 5 days. The cell morphology was observed under inverted microscope. The cell proliferation was evaluated by cell counting kit-8 assay. The expression levels of PI3K and AKT proteins were detected by western blot assay.

    RESULTS AND CONCLUSION: Guishen Pill significantly increased the cell proliferation in the Guishen Pill groups in a dose- and time-effect manner. The proliferation of bone marrow mesenchymal stem cells in the 80 mg/L Guishen Pill group was strongest at the 3rd day. The expression levels of PI3K and AKT proteins in the Guishen Pill groups were significantly higher than those in the blank control group. In summary, Guishen Pill water extract can effectively boost the proliferation of bone marrow mesenchymal stem cells, which may be related to its involvement in regulating PI3K/AKT signaling pathway.

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    miRNA expression profiling of osteogenic differentiation of bone marrow mesenchymal stem cells induced by microchannel porous hydroxyapatite scaffold
    Zheng Jiajun, Qing Wei, Huang Lijuan, Ren Jing, Liu Chunhui, Peng Pairan, Huang Jie, Mu Yandong
    2020, 24 (13):  1989-1995.  doi: 10.3969/j.issn.2095-4344.2053
    Abstract ( 480 )   PDF (1000KB) ( 68 )   Save

    BACKGROUND: Porous hydroxyapatite scaffolds have good osteogenesis in vivo and in vitro. However, little research has been done on the complex regulation mechanisms of miRNAs involved.

    OBJECTIVE: To investigate the changes of related miRNA expression in rat bone marrow mesenchymal stem cells during osteogenic mineralization by porous hydroxyapatite scaffolds.

    METHODS: Rat bone marrow mesenchymal stem cells were isolated, cultured and identified in vitro. Bone marrow mesenchymal stem cells co-cultured with porous hydroxyapatite scaffold were as experimental group, and bone marrow mesenchymal stem cells cultured alone served as blank control group, both of which underwent osteogenic induction for 7 days. During the osteogenic mineralization, miRNA high-throughput sequencing technology was used to analyze the changes of miRNA expression profiles followed by GO analysis. The miRNA molecules with obvious expression differences were screened and verified by qRT-PCR.

    RESULTS AND CONCLUSION: (1) Compared with the blank control group, in the experimental group, the expression levels of BMP2, ALP and Runx2 mRNA were up-regulated, and the expression level of BMP2 was up-regulated significantly (P < 0.05). (2) Results of miRNA high-throughput sequencing showed that 13 miRNAs such as miR-210-3p and miR-146a-5p were up-regulated, and 17 miRNAs such as let-7c-3p and let-3615 were down-regulated significantly. (3) GO analysis revealed that up-regulated miRNA target genes were mainly involved in biological regulation, cellular gene expression, and gene expression regulation, mainly including nuclear factor-κB, Toll-like receptor 9, intercellular adhesion, interleukin-1 regulation, and signaling pathways such as angiogenesis and Hippo. (4) Real-time fluorescence quantitative qPCR results showed that miRNA-210 was up-regulated 15 times and miR-146a-5p was up-regulated 10 times in the experimental group (P < 0.05). These results indicate that the new microchannel porous hydroxyapatite scaffold can promote the differentiation of bone marrow mesenchymal stem cells by up-regulating miRNA-210-3p and miR-146a.

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    Therapeutic effect of human adipose stem cells derived exosomes on carbon tetrachloride induced liver fibrosis in rats 
    Li Hongchao, Wang Xi, Li Li, Li Zhenyu, Zang Zusheng, Zhou Heng, Wang Xiaojin, Chen Chengwei, Cheng Mingliang, Wu Jun, Jin Yinpeng, Fu Qingchun
    2020, 24 (13):  1996-2004.  doi: 10.3969/j.issn.2095-4344.2048
    Abstract ( 358 )   PDF (1441KB) ( 95 )   Save

    BACKGROUND: Liver fibrosis has higher morbidity and mortality. Activation and proliferation of hepatic stellate cells is a key link in the progression of liver fibrosis. At present, there are still no effective anti-fibrosis agents targeting single links or targets.

    OBJECTIVE: To analyze the effect of human adipose stem cells derived exosomes on rats with liver fibrosis induced by carbon tetrachloride.

    METHODS: Human adipose stem cells were obtained from healthy people by enzyme dissolution method. After in vitro culture, human adipose stem cells derived exosomes were obtained by multiple ultrafiltration. Different concentrations of exosomes were used to treat the hepatic stellate cells activated by transforming growth factor β1. The human adipose stem cells activated by transforming growth factor β1 were treated with different concentrations of exosomes. The expression of α-smooth actin in the cells was detected by quantitative PCR, and the growth and apoptosis of activated hepatic stellate cells were detected by CCK-8 and flow cytometry respectively. Rat models of liver fibrosis were established by intraperitoneal injection of carbon tetrachloride and treated by tail vein injection of exosomes. Rat liver function, serum levels of type III procollagen and type IV collagen, and Ishak score were determined. Semi-quantitative analysis of liver fibrosis was performed. The expression levels of tissue inhibitor of matrix metalloproteinase-1, matrix metalloproteinase 9 and α-smooth actin in liver tissue were measured by immunofluorescence method. The study protocol was approved by the Animal Ethics Committee and Medical Ethics Committee, Tongji University, China in January, 2017.

    RESULTS AND CONCLUSION: Human adipose stem cells derived exosomes inhibited the proliferation of activated hepatic stellate cells. The possible mechanism is to inhibit the proliferation of activated macrophages, reduce the production of collagen fibers, α-smooth actin actin, and tissue inhibitor of matrix metalloproteinase-1, and to increase the expression of matrix metalloproteinase 9. These findings suggest that exosomes can be used to treat carbon tetrachloride induced liver fibrosis.

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    Extension and dentin differentiation potential of dental pulp stem cells from human deciduous teeth on the stiff matrix surface  
    Li Zhangyi, Liu Fengting, Huang Jianyong, Su Xiaoying, Wang Zhixing, Zheng Quan, Li Yanxia, Liu Xiaozhi
    2020, 24 (13):  2005-2010.  doi: 10.3969/j.issn.2095-4344.2058
    Abstract ( 353 )   PDF (751KB) ( 145 )   Save

    BACKGROUND: Dental pulp stem cells can differentiate into dentin under appropriate induction conditions, which are important seed cells in dental tissue engineering. However, the commonly used inducers are chemical agents, which are not available for in vivo application. Mesenchymal stem cells can differentiate with the material hardness, and the physical property-induced cell differentiation is little reported.

    OBJECTIVE: To observe the extension characteristics and dentin differentiation potential of dental pulp stem cells from human deciduous teeth on the stiff matrix surface.

    METHODS: Dental pulp stem cells from naturally shed deciduous teeth were isolated, cultured and identified. Four solid gel matrixes with elasticity modulus of (9.12±0.94), (27.18±3.55), (59.37±4.05) and (86.45±5.33) kPa were made using low melting point agarose. The extension ability of passage 4 dental pulp stem cells on the surface of the above solid matrixes was detected by two-dimensional clone formation and cell scratch tests. The protein expression levels of dentin matrix protein-1, dentin phosphoprotein and dentin sialoprotein were detected by western blot assay.

    RESULTS AND CONCLUSION: Dental pulp stem cells from human deciduous teeth seeded on the gel matrix with extremely low and low hardness almost existed as cell clones with neat edges, and cell spreading and extension were rare. When seeded on the gel matrix with moderate and high hardness, the cloned edge of deciduous dental pulp stem cells spread and extended obviously. The cell body became large and the cell edge extended significantly. The cell scratch test revealed the similar phenomenon. When seeded on the gel matrix with moderate and high hardness, dental pulp stem cells from human deciduous teeth exhibited high expression levels of of dentin matrix protein-1, dentin phosphoprotein and dentin sialoprotein. In summary, with the increase of matrix hardness, the abilities of extension and differentiation into dentin of dental pulp stem cells from human deciduous teeth are increased gradually, which provides a method for dental tissue engineering.

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    Proteomics analysis of exosomes from adipose-derived stem cells in skin damage repair
    Qin Danying, Zhang Yuheng, Li Xueyong, Yang Wenxian
    2020, 24 (13):  2011-2019.  doi: 10.3969/j.issn.2095-4344.2064
    Abstract ( 568 )   PDF (1293KB) ( 263 )   Save

    BACKGROUND: There are lots of researches about using adipose-derived stem cells to promote damage repair, but the studies from the perspective of exosome from adipose-derived stem cells based on proteomics and bioinformatics technologies are rarely reported.

    OBJECTIVE: To analyze the differentially expressed proteins of exosome from adipose-derived stem cells between diabetic patients with leg ulcers and healthy adults through proteomics and bioinformatics technologies, so as to screen out the diagnostic and prognostic landmarks.

    METHODS: Adipose-derived stem cells were obtained from 25 diabetic patients (trial group) with leg ulcers who accepted debridement skin grafting at the Department of Plastic and Burn, Second Affiliated Hospital of Air Force Military Medical University from October 2018 to May 2019 and 10 healthy adults who concurrently accepted liposuction (control group). Exosomes from adipose-derived stem cells were extracted for identification. Three cases were randomly selected from each group for proteomics analysis. LFQ technology was used to conduct quantitative analysis. GO and Pathway analysis for the differentially expressed proteins were performed using clueGO (version 2.5.4) was used to do. The transactional analysis between proteins was conducted (String database, version 11.0, R software clusterProfiler package, FDR < 0.25).

    RESULTS AND CONCLUSION: (1) Totally 231 quantitative differentially expressed proteins were screened out, 31 kinds of which had significant difference. There were 29 down-regulated proteins and 2 up-regulated proteins in the trial group. (2) Differential proteins had a high correlation with nutrition and metabolic diseases. Differentially expressed proteins were mostly expressed in extracellular vesicles and platelet alpha granules and were mainly involved in two biological processes - coagulation process and lipid transport. The main molecular functions of differential proteins were related to enzyme inhibitor activity and heparin binding capacity. (3) The pathway analysis of PPI and KEGG showed that the significantly down-regulated ITGA2B and ITGB3 proteins were closely related to the course of the disease in the trial group, both of which are expected to be the new targets in stem cell treatment for diabetes with leg ulcers.

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    Interferon-gamma combined with lipopolysaccharide polarizes human umbilical cord-derived mesenchymal stem cells to a MSC2 phenotype
    Huang Tian, Huang Xin, Lai Peilong, Geng Suxia, Chen Xiaomei, Wang Yulian, Guo Liyan, Zeng Gaochun, Han Fengzhen, Li Xiaohong, Du Xin, Weng Jianyu
    2020, 24 (13):  2020-2027.  doi: 10.3969/j.issn.2095-4344.2050
    Abstract ( 455 )   PDF (1184KB) ( 300 )   Save

    BACKGROUND: Mesenchymal stem cells have been widely applied in autoimmune diseases and graft-versus-host diseases because of their immunomodulatory capabilities. However, mesenchymal stem cells have plasticity in immunomodulation, which leads to heterogeneity and instability when used in vivo.

    OBJECTIVE: To investigate the polarization of human umbilical cord derived mesenchymal stem cells to an immunosuppressive phenotype (MSC2) in the inflammatory microenvironment induced by interferon-γ and lipopolysaccharide.

    METHODS: Human umbilical cord-derived mesenchymal stem cells were isolated and cultured in vitro, and then were identified by morphological characteristics, surface markers, adipogenesis and osteoinduction activity. Human umbilical cord-derived mesenchymal stem cells were treated with interferon-γ (10 μg/L), lipopolysaccharide (100 μg/L), or their combination for 24 hours, respectively, and were then co-cultured with phytohemagglutinin pre-treated peripheral blood mononuclear cells for 5 days under direct or Transwell indirect contact. The percentages of regulatory T cells and T helper 1 cells were analyzed by flow cytometry at different times. The mRNA expression levels of Toll-like receptors 2, 3 and 4 were detected by real-time fluorescence quantitative PCR.

    RESULTS AND CONCLUSION: (1) Human umbilical cord derived mesenchymal stem cells exhibited spindle-shaped or fibroblast-like morphology, highly expressed CD73, CD90 and CD105, and lacked expression of CD34, CD45 and HLA-DR. (2) Under direct or indirect co-culture, human umbilical cord-derived mesenchymal stem cells pre-treated with interferon-γ and lipopolysaccharide could promote the generation of regulatory T cells, which was superior to the interferon-γ, lipopolysaccharid, un-treated and control groups (P < 0.05). (3) The percentage of T helper 1 cells gradually decreased over time. (4) Under indirect co-culture, human umbilical cord derived mesenchymal stem cells pre-treated with interferon-γ and lipopolysaccharide were polarized into immunosuppressive MSC2 phenotype at an earlier period and highly expressed Toll-like receptor 3 (P < 0.05). (5) In conclusion, the combination of interferon-γ (10 μg/L) and lipopolysaccharide (100 μg/L) results in the high-efficient polarization of mesenchymal stem cells toward the MSC2 phenotype under indirect co-culture, and the immunosuppressive capability of MSC2 is independent of intercellular contact, which provides clinical evidence for the MSC2-derived exosome therapy in the future.

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    Biological characteristics of dental pulp stem cells induced by lipopolysaccharide
    Liu Ying, Gao Jie, Wu Buling
    2020, 24 (13):  2028-2033.  doi: 10.3969/j.issn.2095-4344.2044
    Abstract ( 332 )   PDF (786KB) ( 63 )   Save

    BACKGROUND: During the decay process, the bacteria and toxins invade dental pulp tissue along the dentin tubule. Dental pulp stem cells proliferate and migrate to the damaged point, forming reparative dentin to avoid stimulations from bacteria outside. Lipopolysaccharide is the main component of gram-negative bacteria. Whether lipopolysaccharide affects the proliferation, migration, and odontoblastic ability of dental pulp stem cells remains to be studied.

    OBJECTIVE: To investigate the proliferation, migration and odontoblastic abilities in dental pulp stem cells induced by lipopolysaccharide.

    METHODS: Primary cultured dental pulp stem cells were stimulated by 0, 0.1,1 and 10 mg/L lipopolysaccharide.       The proliferation of dental pulp stem cells was detected by MTT assay. Scratch test and Transwell assay were performed to test the migration of dental pulp stem cells. Dental pulp stem cells were cultured in mineralized solution and 1 mg/L lipopolysaccharide for 21 days. The mineralized nodule formation was detected by alizarin red staining. RT-PCR was performed to detect the expression of dentin related genes.

    RESULTS AND CONCLUSION: The absorbance value in the 0.1, 1 and 10 mg/L lipopolysaccharide groups at 1, 3, 5 and 7 days was significant lower than that in the 0 mg/L lipopolysaccharide group (P < 0.01), and the migration ability was higher than that in the 0 mg/L lipopolysaccharide group. After 12 days of mineralized induction, the number and area of mineralized nodule formation in the 1 mg/L lipopolysaccharide group were significantly lower than those in the 0 mg/L lipopolysaccharide group (P < 0.01). The mRNA expression levels of osteocalcin, bone sialoprotein, and alkaline phosphatase in the 1 mg/L lipopolysaccharide group were significantly lower than those in the  0 mg/L lipopolysaccharide group (P < 0.01). These results indicate that lipopolysaccharide treatment inhibits the proliferation and odontoblastic ability of dental pulp stem cells but promotes the cell migration ability. 

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    Umbilical cord mesenchymal stem cells for the treatment of refractory chronic graft-versus-host disease
    Zhang Ling, Sun Yanling, Wang Xiaozhen, Long Bing , Liu Jiajun
    2020, 24 (13):  2034-2038.  doi: 10.3969/j.issn.2095-4344.2039
    Abstract ( 526 )   PDF (593KB) ( 55 )   Save

    BACKGROUND: Chronic graft-versus-host disease is the most common complication after transplantation and glucocorticoid is a first-line drug. Glucocorticoid in combination with immunosuppressive therapy is not effective in half of the patients with hormone resistant chronic graft-versus-host disease. The low immunogenicity of umbilical cord mesenchymal stem cells provides the possibility for clinical treatment of graft-versus-host disease.

    OBJECTIVE: To investigate the clinical efficacy and safety of umbilical cord-derived mesenchymal stem cells to treat refractory chronic graft-versus-host disease. 

    METHODS: Fifteen patients with refractory chronic graft-versus-host disease received mesenchymal stem cell infusion treatment based on immunosuppressive therapy. The therapeutic efficacy, infusion-related adverse reactions, and survival were analyzed. The ratio change of peripheral blood lymphocytes was determined by flow cytometry. This study was approved by Medical Ethics Committee, Third Affiliated Hospital of Sun Yat-sen University in China.

    RESULTS AND CONCLUSION: There were 12 male and 3 female patients with a median age of 29 years (ranging from 17 to 52 years). Four patients obtained complete response, seven patients obtained partial response, 11 had overall response, and four patients had no response. After treatment by umbilical cord mesenchymal stem cells, the ratio of CD19+ cells in the peripheral blood was slightly, but not significantly lower, but CD19+CD27+ and CD3+ cell ratios were slightly, but not significantly higher than those before treatment. No patients had adverse reactions related to infusion of umbilical cord mesenchymal stem cells and no patients had primary disease recurrence and mesenchymal stem cell-related tumor. These findings suggest that umbilical cord-derived mesenchymal stem cell infusion is an effective and safe therapy for refractory chronic graft-versus-host disease. 

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    Regulatory effect of uncarboxylated osteocalcin on osteogenic and adipogenic differentiation of mouse bone marrow mesenchymal stem cells under high-glucose conditions
    Liu Zhongsheng, Yang Jianhong
    2020, 24 (13):  2039-2046.  doi: 10.3969/j.issn.2095-4344.2032
    Abstract ( 530 )   PDF (1364KB) ( 50 )   Save

    BACKGROUND: The method of promoting osteogenic differentiation of bone marrow mesenchymal stem cells under high-glucose conditions to inhibit adipogenic differentiation can provide prevention and treatment ideas for the treatment of bone metabolic diseases such as diabetic osteoporosis.

    OBJECTIVE: To explore the effects of uncarboxylated osteocalcin on adipogenic and osteogenic differentiation of mouse bone marrow mesenchymal stem cells under high-glucose conditions so as to reveal the action mechanism of uncarboxylated osteocalcin on the differentiation of bone marrow mesenchymal stem cells.

    METHODS: Mouse bone marrow mesenchymal stem cells were cultured by whole bone marrow culture and adherent purification. Cells were treated with uncarboxylated osteocalcin at different concentrations (0, 1, 3, 10, and 30 μg/L). Cell proliferation was detected by cell counting kit-8 to determine the best mass concentration. Passage 3 bone marrow mesenchymal stem cells were incubated with adipogenic (or osteogenic) differentiation medium, and assigned to four groups: control group, high glucose group, uncarboxylated osteocalcin group, and high glucose + uncarboxylated osteocalcin group. Corresponding groups received the addition of 25.5 mmol/L exogenous glucose and 3 μg/L uncarboxylated osteocalcin. Lipid droplets and calcium nodules were detected by oil red and alizarin red staining. Quantitative reverse transcription-polymerase chain reaction was used to detect the relative expression levels of adipogenic marker genes (Fabp4, PPARγ, Adipsin and FAS) and osteogenic differentiation marker genes (Runx2, Osx, alkaline phosphatase, and type I collagen). Kits were used to detect alkaline phosphatase activity and type I collagen levels. The relative expression levels of P-Erk and P-AMPKα were detected using signal pathway specific inhibitors (PD98059 and BML) and western blot assay. 

    RESULTS AND CONCLUSION: (1) Uncarboxylated osteocalcin 3 μg/L promoted cell proliferation (P < 0.01). (2) Uncarboxylated osteocalcin promoted the formation of calcium nodules (P < 0.01) in bone marrow mesenchymal stem cells under high-glucose conditions but inhibited the formation of lipid droplets (P < 0.05), down-regulating the relative expression levels of adipogenic marker genes (PFabp4 < 0.01; PPPARγ < 0.05; PAdipsin < 0.01; PFAS < 0.01), but increasing the relative expression levels of osteogenic differentiation marker genes (PRunx2 < 0.05; POsx < 0.05; PALP < 0.01; PCOLI < 0.01). Uncarboxylated osteocalcin increased alkaline phosphatase activity (P < 0.01) and type I collagen level (P < 0.05). (3) Uncarboxylated osteocalcin up-regulated the expression levels of P-Erk (P < 0.01) and P-AMPKα (P < 0.01) under high-glucose conditions. (4) These results indicate that uncarboxylated osteocalcin promoted osteogenic differentiation of bone marrow mesenchymal stem cells under high-glucose conditions through Erk/AMPKα signaling pathway and inhibited adipogenic differentiation.

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    In vitro hematopoietic support of human umbilical cord blood CD34+ cells by human skeletal muscle-derived pericytes/perivascular cells
    Yang Xiaoping, Yang Tingting, Gu Jingjing, Zhou Rui, Xu Fei, Yang Jihui, Zheng Bo
    2020, 24 (13):  2047-2054.  doi: 10.3969/j.issn.2095-4344.2065
    Abstract ( 365 )   PDF (1202KB) ( 60 )   Save

    BACKGROUND: Perivascular cells have been shown to be the precursor cells of mesenchymal stem cells, which regulate the behavior of hematopoietic stem cells and support hematopoiesis through cell-to-cell contact or paracrine effects. Hematopoietic support of human skeletal muscle-derived pericytes/perivascular cells (hMD-PCs) remains to be studied.

    OBJECTIVE: To identify the biological characteristics of hMD-PCs isolated from human skeletal muscle and to study their supporting effect on umbilical cord blood CD34+ cells in vitro.

    METHODS: (1) hMD-PCs with phenotype CD146+CD56-CD34-CD144-CD45- were sorted from human skeletal muscle by enzymatic digestion and multiparameter fluorescence-activated cell sorting, and their biological characteristics were identified. (2) The in vitro culture system of umbilical cord blood CD34+ cells co-cultured with human CD146+ hMD-PCs (experimental group) or with human bone marrow mesenchymal stem cells (positive control group) was established. After 1, 2 and 4 weeks of co-culture, the number of cells, the colony formation ability and immunophenotype were measured and statistically analyzed.

    RESULTS AND CONCLUSION: (1) CD146+ hMD-PCs were sorted by multiparameter fluorescence-activated cell sorting and the purity was (91.5±1.85)% (n=5). CD146+ hMD-PCs expressed mesenchymal surface markers CD73, CD90, CD105, CD44, and did not express hematopoietic cell and endothelial cell markers CD45, CD34, and CD31. After induced culture, CD146+ hMD-PCs could differentiate into osteoblasts, chondrogenesis, adipocytes and myoblasts. (2) There were no significant differences in the cell number, colony formation ability or immunophenotype (CD45+, CD34+CD33-, CD14+, CD10+/CD19+) between experimental and positive control groups (P > 0.05, n=6). The number of cells in the blank control group without feeder was significantly decreased at 1 week of culture, and there was almost no cell survival at 2 weeks of culture. (3) In summary, CD146+ hMD-PCs, like human bone marrow mesenchymal stem cells, have hematopoietic support capacity in vitro.

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    The system for directional and stable differentiation of amniotic fluid stem cells into neuron-like cells
    Zong Ling, Chen Guangui, Zhang Lanzhen, Zhai Jinming, Long Yanbo, Liu Xiaolan
    2020, 24 (13):  2055-2060.  doi: 10.3969/j.issn.2095-4344.2059
    Abstract ( 460 )   PDF (770KB) ( 100 )   Save

    BACKGROUND: Neuronal regeneration using stem cell differentiation has gained a lot of attentions from researchers. Although embryonic stem cells and induced pluripotent stem cells have good potential for neuronal differentiation, a high risk of tumor development in vivo limits the further study.

    OBJECTIVE: To establish a stable system for sorting, culture and neuronal differentiation of amniotic fluid stem cells, and to explore the feasibility as seed cells for neuronal regeneration.

    METHODS: Amniotic fluid sample (10 mL) was obtained at 19-22 weeks of pregnancy under B-ultrasound guidance, and amniotic fluid stem cells were isolated by c-Kit magnetic beads. The markers Oct-4 and Sox2 of amniotic fluid stem cells were identified by immunofluorescence. The expression levels of c-Kit, Oct-4, Sox2 and Nestin in amniotic fluid stem cells after multiple passages were detected by RT-PCR. Then, the cells were cultured by hanging drop for 4 days to observe the embryoid bodies-like structures. Amniotic fluid stem cells were induced to differentiate into neurons using two-stage method. The expression levels of Neuro D and Tuj1 were observed by immunofluorescence.

    RESULTS AND CONCLUSION: (1) About 1% of amniotic fluid stem cells were positive for c-Kit. (2) (75.0±4.6)% of amniotic fluid stem cells expressed Oct-4 and (86.0±2.8)% of the cells expressed Sox2. (3) The expression levels of c-Kit, Oct-4, Sox2 and Nestin detected by RT-PCR did not change with passage times. (4) Embryoid bodies-like structures formed after hanging drop culture. (5) Immunofluorescence results showed that amniotic fluid stem cells expressed neuronal marker Tuj1, but without the typical morphological features. RT-PCR detected the expression of Tuj1 in different amniotic fluid stem cell specimens as well as in the same sample after several passages. (6) Amniotic fluid stem cells could have the characteristics of neuron-like cells after induction with basic fibroblast growth factor, brain-derived neurotrophic factor, and neurotrophin factor 3 in two stages, and could express neural stem cell marker Neuro D and neuronal marker Tuj1.

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    Acellular amniotic membrane scaffold combined with human amniotic mesenchymal stem cells transfected with Scleraxis lentivirus can promote tendon-bone healing in rabbits
    Zhang Jun, Yang Jibin, Jin Ying, Zou Gang, Tang Jingfeng, Ge Zhen, Yang Qifan, Liu Yi
    2020, 24 (13):  2061-2067.  doi: 10.3969/j.issn.2095-4344.2060
    Abstract ( 408 )   PDF (1015KB) ( 61 )   Save

    BACKGROUND: Acellular amniotic membrane scaffold is a natural scaffold with good biocompatibility, which has been widely used in tissue engineering. Scleraxis can promote the differentiation of human amniotic mesenchymal stem cells into human ligament cells and promote tendon-bone healing.

    OBJECTIVE: To explore whether acellular amniotic membrane scaffold combined with human amniotic mesenchymal stem cells transfected with Scleraxis can promote rabbit tendon-bone healing.

    METHODS: (1) Human amniotic mesenchymal stem cells were isolated and cultured in vitro. After passaged, the cell morphology was observed. (2) The Scleraxis lentivirus was constructed in vitro and then transfected into passage 3 human amniotic mesenchymal stem cells with optimal multiplicity of infection. The transfection efficiency was detected by q-PCR. (3) The acellular amniotic membrane scaffold was prepared by enzymatic digestion. Then the Scleraxis lentivirus-transfected cells were seeded on the acellular amniotic membrane scaffold in vitro. The cell growth on the scaffold was observed by phalloidin staining. (4) The New Zealand white rabbit tendon was covered with the acellular amniotic membrane scaffold combined with human amniotic mesenchymal stem cells transfected with Scleraxis lentivirus, followed by implanted into the bone tunnel. The tendon-bone healing was detected.

    RESULTS AND CONCLUSION: The passage 3 human amniotic mesenchymal stem cells adhered well. (2) After transfected with Scleraxis lentivirus for 96 hours, stable green fluorescence was observed. The mRNA expression level of Sclerxis was significantly increased, indicating a success transfection. The epithelial cells of the acellular amniotic membrane scaffold disappeared, indicating a relatively complete decellularization. The basal layer remained intact, and the extracellular matrix component still existed. Phalloidin staining results revealed that the cells on the acellular amniotic membrane scaffold were in good adhesion and growth, and the cell proliferation was not affected. Therefore, In vivo experimental results reveal that human acellular amniotic scaffold combined with human amniotic mesenchymal stem cells transfected with Scleraxis lentivirus can promote the tendon-bone healing.

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    Immunoregulation of allograft rejection: a role played by human CD200+ sub-population from human placenta-derived mesenchymal stem cells
    Liu Ting, Yang Tingting, Ma Xiaona, Ma Haibin, Jin Yiran, Liang Xueyun
    2020, 24 (13):  2068-2073.  doi: 10.3969/j.issn.2095-4344.2061
    Abstract ( 409 )   PDF (656KB) ( 49 )   Save

    BACKGROUND: Immune rejection of skin allograft is a clinical problem to be solved. Our previous study has shown that human placenta-derived CD200+ mesenchymal stem cells may have a strong capability of immunoregulation.

    OBJECTIVE: To investigate the effects of human placenta-derived CD200+ mesenchymal stem cells on rejection of skin allograft.

    METHODS: Skin allograft models of c57/BL6 mice were established and divided into three groups as control group, human placenta-derived mesenchymal stem cells group (PMSCs group), and CD200+ mesenchymal stem cells group (CD200+-PMSCs group). PBS (control group), normal PMSCs and CD200+-PMSCs were injected into the mice through the tail vein, respectively. The necrotic time, survival time and situation of grafted skin were observed. The number of peripheral white blood cells was counted after 7 days of treatment. The expression levels of interleukin-10, interferon-γ and tumor necrosis factor-α were detected by Q-PCR and ELISA.

    RESULTS AND CONCLUSION: (1) Compared with the control group, in the PMSCs and CD200+-PMSCs groups, the condition of skin allograft was better, and the survival time was significantly prolonged (P < 0.001). The condition and survival time of skin allograft in the CD200+-PMSCs group were significantly superior to those in the PMSCs group (P < 0.01). (2) After 7 days of treatment, the number of peripheral white blood cells in the PMSCs and CD200+-PMSCs groups was significantly less than that in the control group (P < 0.01). (3) Compared with the control group, the mRNA expression level of interleukin-10 in the spleen was significantly increased in the CD200+-PMSCs group (P < 0.05), and the mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen were significantly down-regulated in the PMSCs and CD200+-PMSCs groups (P < 0.05, P < 0.01). The mRNA expression levels of interferon-γ and tumor necrosis factor-α in the spleen in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.01, P < 0.05). (4) Compared with the control group, the expression level of interleukin-10 in the blood was significantly increased (P < 0.05, P < 0.001), and the expression levels of interferon-γ and tumor necrosis factor-α in the blood were significantly down-regulated in the CD200+-PMSCs and PMSCs groups (P < 0.05, P < 0.001; P < 0.01, P < 0.001). The expression levels of interferon-γ and tumor necrosis factor-α in the blood in the CD200+-PMSCs group were significantly lower than those in the PMSCs group (P < 0.05). These results indicate that human placenta-derived mesenchymal stem cells have immunosuppressive effect on the rejection of skin allograft, and CD200+ cells may have better immunoregulatory effects by regulating the expressions of interleukin-10, interferon-γ and tumor necrosis factor-α．

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    Mechanism of angelica polysaccharide regulating mitochondrial apoptosis for improving bone marrow failure
    Zhong Ping, Cui Xing
    2020, 24 (13):  2074-2079.  doi: 10.3969/j.issn.2095-4344.2055
    Abstract ( 514 )   PDF (810KB) ( 161 )   Save

    BACKGROUND: Bone marrow failure is an important pathogenesis of aplastic anemia, and how to reverse bone marrow failure is an issue of concern.

    OBJECTIVE: To investigate the regulatory effect of angelica polysaccharide on the mitochondrial dysfunction in murine aplastic anemia.

    METHODS: Seventy-two ICR mice were randomly divided into control, model and treatment groups (n=24 per group). The mice in the latter two groups were used to establish the aplastic anemia models by 60Co γ radiation, intraperitoneal injection of cyclophosphamide and intragastric administration of chloramphenicol, and were then given normal saline or 200 mg/kg angelica polysaccharide for 2 weeks, respectively. The control mice received no intervention. At 1, 7 and 14 days after modeling, peripheral blood cells and bone marrow mononuclear cells were counted, and mitochondrial ultrastructure of the bone marrow was observed by transmission electron microscopy. After Lin- Sca-1+c-Kit+ (LSK) cells were sorted from bone marrow cells, which were hematopoietic stem cells. The mitochondrial membrane potential, levels of reactive oxygen species, and the expression levels of Bcl 2, Bax, cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were detected.

    RESULTS AND CONCLUSION: Compared with the control group, in the model and treatment groups, there were obvious abnormalities in the peripheral blood routine test was the number of bone marrow mononuclear cells was decreased significantly, the mitochondrial number, mitochondrial membrane potential and Bcl 2/Bax ratio were decreased, and the level of reactive oxygen species and the expression of cleaved caspase-9, cleaved caspase-3 and p38 in LSK cells were significantly increased (P < 0.05). After angelica polysaccharide treatment, all above results were significantly improved as compared with the model group (P < 0.05). To conclude, angelica polysaccharide might improve hematopoietic function by up-regulating the mitochondrial membrane potential, increasing the mitochondrial membrane stability and reversing the levels of apoptotic factors.

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    Scleraxis lentivirus-transfected human amniotic mesenchymal stem cells promote tendon-bone healing in rabbits
    Zou Gang, Zhang Jun, You Qi, Tang Jingfeng, Jin Ying, Yang Jibin, Zhu Xizhong, Liu Yi
    2020, 24 (13):  2080-2086.  doi: 10.3969/j.issn.2095-4344.1867
    Abstract ( 261 )   PDF (949KB) ( 39 )   Save

    BACKGROUND: Human amniotic mesenchymal stem cells have a wide variety of sources, low immunogenicity, and multilineage differentiation potential. Studies have confirmed that Scleraxis gene can induce human amniotic mesenchymal stem cells to differentiate into ligaments and accelerate tendon-bone healing.

    OBJECTIVE: To explore whether Scleraxis induces human amniotic mesenchymal stem cells to promote tendon-bone healing in vivo in rabbits, providing new options for clinical treatment of tendon-bone healing.

    METHODS: The study protocol was approved by the Ethic Committee of the Affiliated Hospital of Zunyi Medical University, and written informed consent was obtained from each puerpera. The healthy full-term maternal placenta was taken and cultured, and human amniotic mesenchymal stem cells were isolated and cultured by trypsin digestion twice. Then the morphology of the cells was observed under an inverted microscope, and the cells were further cultured until the third generation for subsequent experiments. The lentivirus carrying the Scleraxis gene was transfected into human amniotic mesenchymal stem cells in vitro. Expression levels of ligament-related genes were detected by real-time fluorescent quantitative PCR, and the expression levels of related proteins were detected by immunofluorescence. Human amniotic mesenchymal stem cells transfected with Scleraxis gene were injected into the extraarticular tendon-bone model of rats. After 3 months, specimens were taken to observe the tendon-bone healing.

    RESULTS AND CONCLUSION: (1) Human amniotic mesenchymal stem cells from passage to third generation showed long fusiform and vortex-like adherent growth under the inverted phase contrast microscope. (2) The third-generation human amniotic mesenchymal stem cells expressed green fluorescence after 24 hours of infection with the Scleraxis gene lentivirus, and the fluorescence expression was strong and stable. (3) Cell counting kit-8 findings indicated that lentivirus transfection of Scleraxis gene showed no influence on the cell growth rate. (4) Real-time fluorescent quantitative PCR findings showed that the mRNA expression of Scleraxis and ligament-related genes type I collagen, type III collagen, Fibronectin and Tenascin-C was significantly increased after lentivirus transfection of Scleraxis gene. (5) The results of immunofluorescence showed that the expression levels of ligament-related proteins type I collagen, type III collagen, Fibronectin and Tenascin-C were increased after lentivirus transfection of Scleraxis gene. To conclude, in vivo animal experiments have confirmed that the lentivirus transfection of Scleraxis gene can accelerate the tendon-bone healing of the rabbit extraarticular tendon-bone model.

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    Detection methods of mesenchymal stem cells-derived exosomes 
    Yang Qinxin, Wang Dali, Wei Xue
    2020, 24 (13):  2087-2094.  doi: 10.3969/j.issn.2095-4344.2063
    Abstract ( 478 )   PDF (829KB) ( 74 )   Save

    BACKGROUND: Mesenchymal stem cells-derived exosomes have been applied in the diagnosis and treatment of various diseases due to its many virtues. Therefore, its accurate and effective detection with low cost is critical for disease diagnosis and treatment.

    OBJECTIVE: To introduce the detection methods and newest progress of mesenchymal stem cells-derived exosomes.

    METHODS: WanFang, Baidu Scholar, VIP, CNKI, PubMed, Web of Science, Sinomed, Embase, Cochrane and Web of Knowledge databases were retrieved for the articles concerning the detection methods of mesenchymal stem cells-derived exosomes published between June 1997 and June 2019. The keywords were “mesenchymal stem cells, exosomes, detection methods” in Chinese and English, respectively. The duplicated and poorly correlated articles were excluded, and finally 60 eligible articles were included for analysis.

    RESULTS AND CONCLUSION: (1) The definition and biological characteristics of mesenchymal stem cells are summarized, and mesenchymal stem cells have been found to treat diseases by paracrine approach. (2) The definition and biological characteristics of mesenchymal stem cells-derived exosomes and its potential clinical application are summarized, including immunoregulation in vivo and promotion of tissue regeneration. (3) The commonly used detection methods of mesenchymal stem cells-derived exosomes and the newest progress are reviewed. (4) This review provides experimental basis for the clinical application of mesenchymal stem cells-derived exosomes regarding disease treatment and tissue repair.

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    Research and progress in the correlation between exosomes from different sources and tumorigenesis
    Cui Guoning, Liu Xiping, Hu Junrui, Li Peiqing
    2020, 24 (13):  2095-2101.  doi: 10.3969/j.issn.2095-4344.1866
    Abstract ( 444 )   PDF (819KB) ( 388 )   Save

    BACKGROUND: Exosome is a nanoscale vesicle body secreted by many kinds of cells, such as stem cells, tumor cells, and cancer stem cells. Exosomes contain a large amount of bioactive molecules that mediate the communication between cells.

    OBJECTIVE: To review the correlation between exosomes from different source and tumorigenesis and explore the research trends and directions in the future.

    METHODS: PubMed, CNKI, and WanFang databases were retrieved for relevant articles using the keywords of “exosomes, tumors, bone marrow mesenchymal stem cells, caner stem cells, HH signaling pathway” in English and Chinese, respectively. The search time was from January 2015 to June 2019. Finally, 80 literatures, including 27 English articles and 53 Chinese articles, were included for result analysis.

    RESULTS AND CONCLUSION: Serum-derived exosomes have a potential in the diagnosis of non-small cell carcinoma, hepatocellular carcinoma, gastric cancer, colon cancer, pancreatic cancer and breast cancer, which may become a potential alternative diagnostic marker for tumor detection. Tumor-derived exosomes can regulate tumors by promoting the growth, proliferation, migration and invasion of tumor cells, regulating immunity and the expression of tumor-related genes and proteins. Exosomes derived from stem cells can promote the invasion and metastasis of tumor cells, which may be achieved through the activation of HH signaling pathway. In addition, exosomes derived from cancer stem cells can enhance the resistance of tumor cells to chemotherapy by promoting the expression of tumor-related drug resistance genes. Exploration on the correlation between cancer stem cell-derived exosomes and drug-resistant genes is likely to discover potential targets for tumor treatments.

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    Regulation of osteosarcoma and stem cell-related signaling pathways
    Tao Hai, Guo Weichun
    2020, 24 (13):  2102-2107.  doi: 10.3969/j.issn.2095-4344.2015
    Abstract ( 495 )   PDF (745KB) ( 72 )   Save

    BACKGROUND: Osteosarcoma is the most common primary bone-derived malignancy in children and adolescents. The prognosis of osteosarcoma patients has hardly improved over the past 30 years. It is urgent to develop new strategies and innovative therapies to further improve the survival rate of osteosarcoma patients.

    OBJECTIVE: To explain the latest advances in molecular mechanisms and signaling networks that contribute to the progression and metastasis of osteosarcoma, and provide a theoretical basis for the treatment of osteosarcoma.

    METHODS: The “osteosarcoma, signaling pathway, prognosis, metastasis, drug resistance, Notch, Wnt/β-catenin, Hedgehog, PI3K/Akt/mTOR, BMPs” were as keywords to search the articles in the CNKI and PubMed databases published from February 1999 to February 2019. Totally 586 related articles were retrieved. After reading the title and abstract, irrelevant articles were excluded based on exclusion criteria, and finally 40 eligible articles were included for review.

    RESULTS AND CONCLUSION: Signaling pathways are critical in the regulation of osteosarcoma formation and proliferation. Studies have found that Notch, Wnt/β-catenin, Hedgehog, PI3K/Akt/mTOR and BMP signaling pathways are expressed in osteosarcoma and stem cells, which have an important impact on the occurrence and development of osteosarcoma.

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    Immunomodulatory characteristics of mesenchymal stem cells mediated by inflammatory factors
    Wang Jie, Yu Limei
    2020, 24 (13):  2108-2113.  doi: 10.3969/j.issn.2095-4344.2054
    Abstract ( 656 )   PDF (724KB) ( 91 )   Save

    BACKGROUND: Mesenchymal stem cells possess strong immunomodulatory capacity, mainly involved in the proliferation, differentiation and functional status of immune cells, and the secretion of inflammatory factors. The immunomodulatory capacity of mesenchymal stem cells is regulated by inflammatory factors. As the type and level of inflammatory factors in the microenvironment change, the immune regulation function of mesenchymal stem cells also changes.

    OBJECTIVE: To review the research progress of inflammatory factor intervention in the immune regulation of mesenchymal stem cells.

    METHODS: A computer-based retrieval of PubMed, Elsevier and CNKI databases was performed. The keywords were “mesenchymal stem cells, immune regulation, plasticity, interferon gamma, transforming growth factor beta, interleukin-17, interleukin-35, prostaglandins E2” in Chinese and English, respectively. The articles concerning the effects of inflammatory factor intervention on the immune regulation of mesenchymal stem cells were included.

    RESULTS AND CONCLUSION: After intervention and pre-treatment of interferon-γ, transforming growth factor-β, interleukin-17, interleukin-35 and prostaglandin E2, the biological characteristics of mesenchymal stem cells have also changed. The interventions cannot only reshape the tissue microenvironment and affect the inflammatory response, but also reconstruct the immune balance, which further treats or alleviates the disease progression. Reasonable individualized and differentiated treatments will be performed at different disease stages according to inflammatory and immunological reaction of the disease. All of them are expected to further improve the therapeutic effect of mesenchymal stem cells on immuno-inflammatory diseases.

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    Biological characteristics and differentiation potential of fibroblasts
    Yang Guiran, Wang Fuke, Li Yanlin
    2020, 24 (13):  2114-2119.  doi: 10.3969/j.issn.2095-4344.2052
    Abstract ( 786 )   PDF (665KB) ( 139 )   Save

    BACKGROUND: Tissue engineering technology has emerged to solve the repair and reconstruction of tissues and organs. The selection and application of seed cells become an issue of concern. Fibroblasts are a popular choice in various tissue engineering studies.

    OBJECTIVE: To summarize the biological characteristics of fibroblasts, their multi-potential differentiation and their effects on the proliferation and differentiation of stem cells.

    METHODS: A computer-based research of CNKI (2015-2019) and PubMed (2005-2019) databases was performed for the articles about the biological characteristics of fibroblasts and multipotential differentiation. The articles were systematically summarized and analyzed. The newest research process of multi-potential differentiation of fibroblasts was reviewed.

    RESULTS AND CONCLUSION: Fibroblasts hold strong metabolism and proliferation abilities, which can synthesize and secrete protein. Fibroblasts can differentiate into different cells under different environments, and exhibit the same strong multi-potential differentiation with stem cells. Therefore, it is commonly used in the transdifferentiation, cell culture, injury repair and tissue engineering, and their effects on promoting proliferation and inducing differentiation of stem cells are particularly significant. We should fully utilize the biological characteristics and multi-potential differentiation of fibroblasts, and co-culture of fibroblasts with stem cells can provide seed cells for tissue engineering, which further provide an idea for traumatic repair in clinic.

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    Insight into white matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocyte
    Zhao Hong, Wang Suping, Lian Jianwen
    2020, 24 (13):  2120-2125.  doi: 10.3969/j.issn.2095-4344.1851
    Abstract ( 724 )   PDF (774KB) ( 291 )   Save

    BACKGROUND: In previous studies Alzheimer’s disease was considered as a typical disease of the brain gray matter, and most attention has focused on the pathological and neuroimaging changes of gray matter in Alzheimer’s disease. Recently, in addition to neuronal loss, white matter degeneration and demyelination may be important pathophysiological features in the progress of Alzheimer’s disease. To date, much attention has been paid to the changes of white matter in Alzheimer’s disease.

    OBJECTIVE: To elucidate the evidence for extensive white matter abnormalities in Alzheimer’s disease and its mechanism, and to discuss the relationship between white matter changes and cognitive function.

    METHODS: A computer-based retrieval was performed by the first author in PubMed and CNKI databases to search related papers published from January 1998 to April 2019 using the keywords of “Alzheimer’s disease, white matter injury, neurodegeneration, oligodendrocyte” in English and Chinese, respectively. Articles related to Alzheimer’s disease, white matter abnormalities, the mechanism of oligodendrocyte death and the relationship between white matter changes and cognitive function were selected. A total of 41 relevant literatures were retrieved.

    RESULTS AND CONCLUSION: White matter abnormalities widely occur in Alzheimer’s disease patients, which are probably the earliest pathological changes. White matter lesions are of important significance in the pathology and pathogenesis of Alzheimer’s disease. Several mechanisms such Aβ toxicity and tauopathy, oxidative stress, excitotoxicity, and iron overload can affect oligodendrocytes, resulting in myelin loss. Altering axonal conduction by demyelination or axonal damage can directly and/or indirectly affect cognition. In conclusion, white matter changes are closely related to cognitive impairment. Explorations on the relationship between white matter changes and the hallmark of Alzheimer’s disease cannot only provide theoretical evidence for Alzheimer’s disease pathogenesis, but also develop a new therapeutic approach for Alzheimer’s disease.

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    Changes of cardiac function in rats with myocardial infarction after umbilical cord-derived mesenchymal stem cell transplantation: a meta-analysis  

    Chen Siyu, Zhang Tao, Yin Wenjuan, Cai Lei, Li Yannan, Xie Liying, Zuo Lin
    2020, 24 (13):  2126-2132.  doi: 10.3969/j.issn.2095-4344.2049
    Abstract ( 308 )   PDF (848KB) ( 74 )   Save

    BACKGROUND: It has been shown that compared with stem cells from other sources, umbilical cord-derived mesenchymal stem cells have lower immunogenicity, and their application has significant effect in rats with myocardial infarction.

    OBJECTIVE: To systematically evaluate the effects of umbilical cord-derived mesenchymal stem cells on cardiac function of rats with myocardial infarction.

    METHODS: PubMed, Cochrane, Embase, CBM, CNKI, WanFang, VIP and CJD databases were retrieved for the literature concerning umbilical cord-derived mesenchymal stem cells for treating rats with myocardial infarction published before June 2019. Two researchers independently completed literature screening, data extraction and methodological quality evaluation according to the inclusion criteria. Meta-analysis was conducted on Stata 14.0.

    RESULTS AND CONCLUSION: A total of 9 articles were included, involving 216 rats. Meta-analysis showed that: (1) Umbilical cord-derived mesenchymal stem cells significantly increased the left ventricular ejection fraction after myocardial infarction in rats [95% confidence interval (CI) (3.16, 3.76), P < 0.001]. (2) Umbilical cord-derived mesenchymal stem cells significantly increased the left ventricular short axis shortening rate after myocardial infarction in rats [95%CI (0.18, 0.54), P < 0.001]. (3) Umbilical cord-derived mesenchymal stem cells significantly shortened the left ventricular end-diastolic internal diameter [95%CI (-1.90, -0.99), P=0.042] and left ventricular end-systolic internal diameter [95%CI (-6.56, -4.65), P < 0.001]. (4) Umbilical cord-derived mesenchymal stem cells significantly improved the left ventricular end-diastolic volume [95%CI (-2.01, -1.11), P < 0.001] and left ventricular end-systolic volume [95%CI (-3.44, -2.17), P < 0.001]. In summary, umbilical cord-derived mesenchymal stem cell transplantation is effective and safe in the treatment of myocardial infarction in rats. Due to the limitation of the quality of the included literature, the above conclusions need to be validated by high-quality and large-sample randomized controlled trials.

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