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    18 October 2018, Volume 22 Issue 29 Previous Issue    Next Issue
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    Safety of freeze-dried powder of human adipose-derived stem cells and its exosomes
    Li Hong-chao, Jin Yin-peng, Wang Xi, Li Li, Fu Qing-chun
    2018, 22 (29):  4593-4600.  doi: 10.3969/j.issn.2095-4344.0994
    Abstract ( 653 )   PDF (984KB) ( 239 )   Save

    BACKGROUND: With the in-depth study of exosomes, increasing studies have confirmed the effectiveness of exosomes in the treatment of diseases. It is of great importance to stabilize the exosomes and not lose their functions.
    OBJECTIVE: To explore the morphological differences in the exosomes of adipose-derived stem cells stored by freeze-drying technology and conventional cryopreservation and to explore the safety of exosomes for injection.
    METHODS: Human adipose-derived stem cells were isolated and cultured to extract the exosomes. Then, pretreated cells and exosomes were lyophilized. Cell morphology was observed under microscope and the protein content of freeze-dried exosome powder was detected by BCA. The safety of freeze-dried exosome powder was detected through vascular stimulation test, muscle stimulation test, hemolytic test, active systemic anaphylactic test, and passive skin allergy test.
    RESULTS AND CONCLUSION: The exosomes still had an intact membrane after freeze-drying and rehydration. The content of exosomal proteins was in constancy. Freeze-dried exosome powder, exosomes, freeze-dried powder of adipose-derived stem cells, and adipose-derived stem cells were all negative for five safety tests, all of which are safe and reliable for body injection and cause no rejection.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Ulinastatin combined with adipose-derived stromal cell transplantation for treatment of acute intestinal ischemia-reperfusion injury
    Wang Shu-ying
    2018, 22 (29):  4601-4606.  doi: 10.3969/j.issn.2095-4344.0995
    Abstract ( 362 )   PDF (773KB) ( 111 )   Save

    BACKGROUND: Studies have shown that ulinastatin inhibits apoptosis in small intestinal cells and helps relieve intestinal ischemia-reperfusion injury. Transplanted mesenchymal stem cells can migrate and colonize in the damaged intestinal tract, and thereby have a certain therapeutic effect on intestinal ischemia-reperfusion injury. Ulinastatin treatment combined with adipose stem cell transplantation may have synergistic effects and enhance the therapeutic effects.
    OBJECTIVE: To explore the repair effect and possible mechanism of ulinastatin combined with adipose-derived stem cells (ADSCs) transplantation on acute intestinal ischemia-reperfusion injury in rats.
    METHODS: A total of 105 Sprague-Dawley rats were selected, 20 of which were randomly selected as normal control group and received saline enemas and tail vein injection of normal saline. The remaining 85 rats were used to make animal models of acute intestinal ischemia-reperfusion injury, and equally randomized into 4 groups: model group treated with normal saline via tail vein, ADSCs group treated with PKH26 labeled ADSCs suspension via tail vein, ulinastatin group treated with intraperitoneal injection of ulinastatin, and combined treatment group treated with ADSCs suspension via tail vein and intraperitoneal injection of ulinastatin (once a day, for 3 consecutive days). After 3 days of treatment, the colon tissues of rats in each group were taken for hematoxylin-eosin staining, TUNEL staining, RT-PCR detection and western blot assay.
    RESULTS AND CONCLUSION: (1) The positive cells labeled by PKH26 were observed in ADSCs and combined treatment group. (2) Compared with the normal control group, the intestional damage in the model group significantly aggravated and the exfoliated cells of colon tissue were increased in number, while the tissue damage levels were significantly reduced and the exfoliated cells were also reduced in number in the ADSCs group, ulinastatin group and combined treatment group. The most significant improvement in tissue damage was found in the combined treatment group. (3) The number of apoptotic cells was the most in the model group followed by ADSCs and ulinastatin groups, and least in the combined treatment group. (4) The levels of matrix metalloproteinases 2, 9 in the ADSCs and ulinastatin groups were significantly reduced compared with the model group (P < 0.05), but significantly higher than those in the combined treatment group (P < 0.05). In conclusion, matrix metalloproteinases 2, 9 may participate in the process of acute intestinal ischemia-reperfusion injury in rats. ADSCs transplantation combined with ulinastatin have synergistic effects, and can considerably relieve intestinal ischemia-reperfusion injury in rats.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Lentiviral-mediated Runx2 transfection of bone marrow mesenchymal stem cells in the repair of joint injury due to osteoarthritis
    Duan Zhi-bin, Qiu Zhi-qiang, Peng Kun, Xu Ze-min, Cheng Ke, Chen Xiang, Shi Qing-ming
    2018, 22 (29):  4607-4613.  doi: 10.3969/j.issn.2095-4344.0996
    Abstract ( 360 )   PDF (866KB) ( 167 )   Save

    BACKGROUND: Bone marrow mesenchymal stem cells as seed cells can differentiate into chondrocytes and osteoblasts. Runx2 can induce bone marrow mesenchymal stem cells to differentiate and mature into chondrocytes and osteoblasts, thus promoting bone healing.
    OBJECTIVE: To investigate the effect of lentiviral-mediated Runx2 transferred into bone marrow mesenchymal stem cells in the repair of joint injury due to osteoarthritis.
    METHODS: (1) Bone marrow mesenchymal stem cells were isolated and cultured from C57BL/6 mice. Lenti-Runx2-EGFP lentivirus (Runx2 group) was transfected into bone marrow mesenchymal stem cells, lentivirus without Runx2 gene (control group) was transfected, and a blank control group was setup. After 48 hours of transfection, the expression of green fluorescent protein was observed under the fluorescence microscope, and the transfection efficiency was calculated. The stably transfected cell line was screened by purinomycin. (2) A model of osteoarthritis was established in C57BL/6 mice by cutting off the anterior cruciate ligament of the knee joint. All of the model mice were randomly divided into normal saline group, bone mesenchymal stem cell group and Runx2-transfected bone mesenchymal stem cell group. 0.1 mL of normal saline, 0.1 mL of normal saline containing non-transfected bone marrow mesenchymal cells (1×107), or 0.1 mL of normal saline containing Runx2-transfected bone marrow mesenchymal cells (1×107) was injected into the knee joint cavity of mice in the corresponding group, respectively.
    RESULTS AND CONCLUSION: (1) CD90 and CD105 were highly expressed in bone marrow mesenchymal stem cells. The transfection efficiency of Lenti-Runx2-EGFP lentivirus was (88.57±3.07)%, and the stably transfected cell line was screened by puromycin (4 mg/L). (2) The knee articular cartilage of mice was intact with smooth knee articular surface in the Runx2-transfected bone mesenchymal stem cell group, while knee articular cartilage degeneration and uneven knee articular surfaces were observed in the other two groups. (3) The chondrocytes decreased and the cartilaginous layer thinned in bone mesenchymal stem cell group, while a lot of cracks on the surface of the cartilage in the saline group. Runx2-transfected bone mesenchymal stem cell group had many chondrocytes and thickened cartilaginous layer, and the Mankin’s score was significantly lower than the other two groups. (4) The positive rate of type II collagen in Runx2-transfected bone mesenchymal stem cell group was significantly higher than that in the other two groups, while the positive rate of type X collagen was lower than the other two groups. (5) The mRNA and protein expressions of Runx2, bone morphogenetic protein-2, alkaline phosphatase, osteocalcin and osteopontin in Runx2-transfected bone mesenchymal stem cell group were significantly higher than those in the other two groups. To conclude, Runx2-transfected bone marrow mesenchymal stem cells can promote the repair of damaged cartilage, thus providing a new direction for the clinical treatment of osteoarthritis.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Acid etching and anodic oxidation of titanium surface of nanotubes promotes the proliferation and osteogenesis of bone marrow mesenchymal stem cells
    Ma Yan, Zhang Hua, Shang Jian-ping, Jiang Qi
    2018, 22 (29):  4614-4619.  doi: 10.3969/j.issn.2095-4344.0997
    Abstract ( 272 )   PDF (735KB) ( 145 )   Save

    BACKGROUND: In recent years, the biomimetic design of titanium implant surface at micron-nano level has become a research hotspot in the biomaterial research.
    OBJECTIVE: To observe the effect of acid etching and anodic oxidation on the surface morphology of pure titanium and the proliferation and osteogenesis of bone marrow mesenchymal stem cells (BMSCs).
    METHODS: The nanotubes with micron roughness were prepared on the titanium surface by acid etching and anodizing method. The surface morphology of nanotubes with micron roughness was used as experimental group and smooth titanium sample treated by polishing as control group. BMSCs were seeded on the surface of titanium samples and observed using field emission scanning electron microscope. Proliferation of the cells was detected by MTT assay within 7 days of conventional culture. Alkaline phosphatase activity was measured At 3, 7, 14 days after osteogenic induction. Osteogenic marker genes and proteins were detected using RT-qPCR and western blot at 7, 14, 21 days after osteogenic induction.
    RESULTS AND CONCLUSION: The control group had no micron and nano structure surface of the samples, while uneven surface, micron-sized holes, and uniformly distributed nanotube arrays were visible in the experimental group. With the culture time, the number of BMSCs on the sample surface in the two groups was gradually increased, and the cell number in the experimental group was significantly higher than that in the control group at 3, 5, 7 days after culture (P < 0.05). The alkaline phosphatase activity in the experimental group was also higher than that in the control group at 7 and 14 days after osteogenic induction (P < 0.05). Compared with the control group, the expression levels of osteopontin, bone-specific transcription factors, osteocalcin mRNAs and proteins were increased in the experimental group at 7, 14, 21 days after culture. These results suggest that the acid etching and anodic oxidation of the titanium surface of nanotubes can promote BMSCs proliferation and osteogenic differentiation.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Berberine promotes the in vitro migration of bone marrow mesenchymal stem cells via activation of PI3K/AKT pathway
    Li Qiong-jing, Luo Qi
    2018, 22 (29):  4620-4624.  doi: 10.3969/j.issn.2095-4344.0967
    Abstract ( 323 )   PDF (1472KB) ( 270 )   Save

    BACKGROUND: Berberine as the main alkaloid of herbal Coptis chinensis has many pharmacological effects on bone marrow mesenchymal stem cells (BMSCs).
    OBJECTIVE: To explore the effects and mechanism of berberine on the in vitro migration of BMSCs.
    METHODS: Rat BMSCs were isolated and cultured by a whole bone marrow assay, and prepared into 1.5×109/L. Berberine was dissolved by dimethyl sulfoxide, and diluted by α-MEM containing 1 % fetal bovine serum into the concentrations of 1, 3, 10 μmol/L. Cell migration was assessed using a Transwell chamber and cell scratch assay. Western blot assay was used to test the regulatory effect of berberine on p-AKT pathway.
    RESULTS AND CONCLUSION: Berberine had no effect on the cell viability of BMSCs. Berberine at 10 μmol/L significantly promoted the migration of BMSCs. The cell scratch assay shared consistent findings with the Transwell assay. Addition of berberine up-regulated the p-AKT expression in BMSCs, while LY294002, the inhibition of p-AKT, could effectively reverse the pro-migration effects of berberine. Overall, berberine can promote the migration of BMSCs via the activation of PI3K/AKT pathway.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Co-expression of CD24 and CD44 in gastric carcinoma and its influence on clinicopathological parameters and prognosis
    Han Fang-zheng, Zhang Xiao-lin, Dong Wei-yi, Xie Yun-ting
    2018, 22 (29):  4625-4630.  doi: 10.3969/j.issn.2095-4344.0998
    Abstract ( 371 )   PDF (739KB) ( 156 )   Save

    BACKGROUND: Studies have shown that the expression of CD24 and CD44 may be closely related to the disease progression, clinicopathological parameters and prognosis of gastric carcinoma.
    OBJECTIVE: To investigate the expression of CD24 and CD44 in gastric carcinoma and its influence on clinicopathological parameters and prognosis.
    METHODS: The clinical data of patients undergoing surgical resection of gastric carcinoma in Heze Municipal Hospital from April 2006 to April 2012 were collected. The expression of CD24 and CD44 protein in cancer tissues, paracancerous tissues and normal tissues from resected specimens was detected by immunohistochemistry. The relationship between the expressions of CD24 and CD44, clinicopathological parameters and prognosis of the patients was analyzed.
    RESULTS AND CONCLUSION: (1) Among 180 patients, the positive rate of CD24 was 57.5% (92/180), which was lowly expressed in 54 cases and highly expressed in 38 cases; the positive rate of CD44 was 49.3% (79/180), which was lowly expressed in 48 cases and highly expressed in 31 cases. The co-expression rate was 24.3% (39/180) and the double negative rate was 30.0% (48/180). (2) Compared with cancer tissues, the positive rates of CD24 and CD44 in normal gastric tissues and paracancerous tissues were significantly lower (P < 0.001). (3) Univariate analysis showed that the co-expression of CD24 and CD44 in gastric cancer tissues was related to the size of gastric carcinoma, T staging, N staging, vascular invasion (P < 0.05), but not related to age, sex, tumor site, WHO pathological classification, Lauren classification and M staging (P > 0.05). Multivariate analysis showed that T staging and N staging were independent risk factors affecting the expression of CD24 and CD44 in gastric cancer tissues. (4) Spearman rank correlation analysis showed no correlation between the expression intensity of CD24 and CD44 (r=0.020, P=0.795). (5) Seventeen of 180 cases were lost to follow-up, and the loss rate was 9.4%. Eighty-seven patients died within 5 years. Twenty-one of 53 patients in CD24 single-positive group died, and 23 of 40 patients in CD44 single-positive group died. Thirteen of 48 patients in double-negative group died, and 30 of 39 patients in double positive group died. Log-rank test results showed that the survival rate of the four groups was significantly different (χ2=21.72, P < 0.001), and the CD24(+) CD44(+) group had the worst prognosis. To conclude, CD24 and CD44 have higher positive rates in gastric carcinoma, which are closely related with the staging of patients. Moreover, the co-expression of CD24 and CD44 strongly indicates a poor prognosis.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Insulin-like growth factor binding protein-2 promotes the proliferation, migration and invasion of glioma stem cells
    Zhao Wei, Tang Hui, Shao Chuan, Qiao Fei
    2018, 22 (29):  4631-4636.  doi: 10.3969/j.issn.2095-4344.0999
    Abstract ( 320 )   PDF (679KB) ( 129 )   Save

    BACKGROUND: To date, the molecular mechanism of recombinant insulin-like growth factor binding protein 2 (IGFBP-2) on glioma is still unclear. Endogenous IGFBP-2 cannot explain a series of roles of IGFBP-2 in serum, and the roles of exogenous IGFBP-2 should be further elucidated. 
    OBJECTIVE: To observe the effect of IGFBP-2 on the proliferation, migration and invasion of glioma stem cells.
    METHODS: CD133+ glioma stem cells were isolated from U251 human glioma cells by immunomagnetic bead technique. CD133 and nestin expression was detected by immunofluorescence staining. CD133+ glioma stem cells were divided into two groups: the cells were treated with 500 μg/L IGFBP-2 for 48 hours as experimental group, and the cells without intervention of IGFBP-2 as control group. Cell counting kit-8 method was used to detect cell proliferation ability. Transwell chamber assay was used to detect cell migration and invasion ability. Western blot assay was used to detect the expression of PCNA, Aki67, ERK and p-ERK proteins.
    RESULTS AND CONCLUSION: The cell absorbance of the experimental group was significantly higher than that of the control group at 2-5 days of culture (P < 0.05), and the expression of PCNA and Ki-67 in the experimental group was also significantly higher than that in the control group (P < 0.05). The number of migrated cells and invasive cells in the experimental group was significantly higher than that in the control group (P < 0.05). Although there was no difference in the expression of ERK protein between the two groups, the expression of p-ERK protein in the experimental group was significantly higher than that in the control group (P < 0.05). To conclude, IGFBP-2 can promote the proliferation, migration and invasion of glioma stem cells, in which the ERK pathway may play a certain role.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Cryopreserved human umbilical cord mesenchymal stem cells: isolation and culture
    Liu Ting, Jiang Hui, Liu Zhi-hua, Sun Ning, Li Xiao-mei, Weng Jin-sheng
    2018, 22 (29):  4637-4642.  doi: 10.3969/j.issn.2095-4344.0620
    Abstract ( 366 )   PDF (917KB) ( 149 )   Save

    BACKGROUND: Current studies have addressed the mesenchymal stem cells (MSCs) mostly from fresh human umbilical cord, but rarely from cryopreserved human umbilical cord.
    OBJECTIVE: To isolate MSCs from cryopreserved human umbilical cord, and to compare the biological characteristics of human umbilical cord MSCs (hUC-MSCs) harvested using several culture methods.
    METHODS: hUC-MSCs isolated from cryopreserved umbilical cord tissues by explants culture method were cultured in serum-containing and serum-free media. Cell morphology was observed to draw the growth curve of cells in different media. Passage 3 hUC-MSCs cultured in serum-free medium and passage 14 hUC-MSCs in serum-containing medium were selected to detect the expression of surface biomarkers by flow cytometry. Passage 3 cells in the serum-free medium were induced for adipogenic, osteogenic and chondrogenic differentiation, and differentiation marker genes were identified by qPCR. Expression of cytokines in the passage 7 cells cultured in the serum-free medium and in the culture supernatant was detected.
    RESULTS AND CONCLUSION: The hUC-MSCs isolated from cryopreserved human umbilical cord exhibited a spindle-shaped appearance and exuberant growth, and moreover, the cells could be expanded in serum-free medium but the cell proliferation was certainly slower than that in the serum-containing medium. Flow cytometry analysis revealed that the hUC-MSCs were positive for CD73, CD90, CD103, but negative for CD45, CD34, CD14/CD11b, CD79a/CD19, and HLA-DR. Adipogenic (PPARγ), osteogenic (Osteonectin) and chondrogenic (Collagen II) biomarker genes were highly expressed at 14-28 days of induction. Passage 7 hUC-MSC and its supernatant secreted several cytokines including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon α2, chemokine IP-10, interleukin 4, and interleukin-6. In conclusion, we could successfully isolate and expand hUC-MSCs from cryopreserved human umbilical cord tissues.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Measurements of T-cell receptor excision cycles in early stage of immune reconstitution after hematopoietic stem cell transplantation
    Wang Kun, Han Jun-yong, Chen Jin-yan, Liu Shen-min, Xue Shi-jie, Jin Jing-jun
    2018, 22 (29):  4643-4649.  doi: 10.3969/j.issn.2095-4344.0621
    Abstract ( 466 )   PDF (872KB) ( 138 )   Save

    BACKGROUND: Currently, there is no direct and explicit detection index for immune surveillance after hematopoietic stem cell transplantation. The copy number of T-cell receptor excision circle (TREC or signal joint T-cell receptor excision circle, sjTREC) that reflects the recent function of the thymus is monitored by using constantly improved real-time quantitative PCR technology, thereby assessing the level of immune reconstitution and guiding prognosis treatments.
    OBJECTIVE: To analyze the influence of transplantation approach, type of diseases, age, and sex in early stage of immune reconstitution after hematopoietic stem cell transplantation by investigating the level of sjTREC in the peripheral blood.
    METHODS: The number of sjTREC copies per 1 000 cells in the peripheral blood in control group (n=29), before-group (n=19), and after-group (n=6) were detected using absolute quantitative real-time PCR with TaqMan probes.
    RESULTS AND CONCLUSION: In the 1 000 cells, the number of sjTREC copies in the control group was 26.99±29.3 and it decreased with age but no difference existed between male and female. Compared with the control group, the level of sjTREC was significantly lowered in the before-group (P=0.006). After transplantation, the level of sjTREC was rapidly increased within 1 month, and then decreased at 6 months. No obvious differences were found in the level of sjTREC after half-matched HLA related donor transplantation in two cases and full-matched HLA unrelated donor transplantation in four cases. All the findings indicate that the thymus function in patients is seriously impaired before transplantation, and the changes of sjTREC copies that are transiently increased and then decreased at 1 month after transplantation may be related to the stress response of the thymus in the early immune reconstitution period. Although there are no differences between related and unrelated donors, male and female, or different ages, the increased level of sjTREC reflects the changes of thymus function after transplantation, indicating that a variety of factors contribute to immune reconstitution.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Effects of placental mesenchymal stem cell transplantation on behaviors and neurotransmitters in Alzheimer disease rats
    He Jia, Yan Bo, Song Xiao-zheng, Wu Xue-ying
    2018, 22 (29):  4650-4656.  doi: 10.3969/j.issn.2095-4344.0622
    Abstract ( 294 )   PDF (856KB) ( 355 )   Save

    BACKGROUND: A large number of studies have proved that bone marrow mesenchymal stem cell transplantation can promote the recovery of injured nerve function, but the cell source is limited. Moreover, cell collection is extremely traumatic to the human body, and it is very important to find more suitable seed cells.
    OBJECTIVE: To observe the effect of placental mesenchymal stem cell transplantation on behaviors and neurotransmitters in Alzheimer disease rats.
    METHODS: Forty-five male Sprague-Dawley rats were randomly divided into three groups (n=15 per group): normal group without any intervention or treatment, model group and experimental group treated with subcutaneous injection of D-galactose and bilateral hippocampal injection of β-amyloid peptide 25-35. The model of senile Alzheimer disease was established in the latter two groups. After the model was successfully established, placental mesenchymal stem cell suspension (1×108 cells/L, 5 μL) was injected into the hippocampus of the experimental group. The model group did not carry out cell transplantation. Four weeks after transplantation, Morris water maze for behavior observation, brain homogenate neurotransmitter detection and histopathological observation of the hippocampus were carried out.
    RESULTS AND CONCLUSION: (1) Compared with the normal group, the escape latency at different time points in the model group was significantly prolonged (P < 0.05), and the activity path in the target quadrant was decreased (P < 0.05). Compared with the model group, the escape latency at different time points in the experimental group was significantly shortened (P < 0.05), and the activity path in the target quadrant was increased (P < 0.05). (2) Compared with the normal group, the levels of monoamine oxidase and acetylcholinesterase in the brain homogenate increased significantly in the model group (P < 0.05), while the level of choline acetyltransferase decreased significantly(P < 0.05). Compared with the model group, the levels of acetylcholinesterase and monoamine oxidase in the brain homogenate of the experimental group decreased significantly (P < 0.05), and the level of choline acetyltransferase increased significantly (P < 0.05). (3) In the model group, the number of nerves decreased obviously, the cell space increased, the cell body degenerated, the nucleus became pyknosis, the nucleolus was not obvious, and vacuoles appeared in some cells. Compared with the model group, the nerve morphology of the experimental group was relatively complete and tended to be normal. The number of nerves in the experimental group was increased as compared with the model group. To conclude, placental mesenchymal stem cell transplantation can improve the learning and memory abilities of Alzheimer disease rats and regulate the level of neurotransmitters in the rat brain.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Exosomes derived from human umbilical cord mesenchymal stem cells suppress Th22 expression and function
    Li Wei-wei, Li Xiao-feng, Hou Ping, Li Jian-ping
    2018, 22 (29):  4657-4662.  doi: 10.3969/j.issn.2095-4344.0623
    Abstract ( 307 )   PDF (1025KB) ( 136 )   Save

    BACKGROUND: Th22 cells are a novel type of CD4+ helper T cells. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have T cell immunomodulatory function.
    OBJECTIVE: To investigate the Th22 cell immunomodulatory ability of exosomes secreted from hUCMSCs.
    METHODS: hUCMSCs were isolated and cultured, and cell line was authenticated using short tandem repeat (STR) analysis. Exosomes were extracted from the supernatant of passage 4 hUCMSCs. Morphology and particle size of the exosomes were detected under transmission electron microscope. The expression of specific surface marker CD63 and CD81 were detected by western blot. The concentration of exosomes was evaluated by BCA assay. Cell activation cocktail stimulated peripheral blood mononuclear cells from healthy donors were co-cultured with exosomes for 6 hours. The percentage of Th22 cells and the proliferation of CD3+CD4+T cells and CD3+CD8+T cells were detected by flow cytometry. Flow cytometry was also used to test the level of interleukin 22 at 72 hours of co-culture.
    RESULTS AND CONCLUSION: Successfully established hUCMSCs primary cell line could stably passage. Exosomes secreted from hUCMSCs had typical exosomal morphology and marker proteins, and significantly inhibited the proliferation of CD3+CD4+T cells (P < 0.05) and CD3+CD8+T cells (P < 0.01). These exosomes also inhibited the proliferation of Th22 cells, and reduced the level of interleukin 22 in the cells (P < 0.01). These findings indicate that exosomes secreted from hUCMSCs inhibit Th22 cell expression and function, and have the immunomodulatory function of Th22 cells in vitro, which can be a new therapeutic agent for the treatment of immune disorders.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Regression of liver fibrosis after adipose-derived mesenchymal stem cell transplantation via different approaches: an objective standard comparison
    Gu Chun, Yu Xiao-jiong, Dong Ke, Xiong Wei, Peng Sheng-kun
    2018, 22 (29):  4663-4668.  doi: 10.3969/j.issn.2095-4344.0624
    Abstract ( 355 )   PDF (1071KB) ( 173 )   Save

    BACKGROUND: The choice of transplant approach may directly affect the therapeutic effect of stem cell transplantation on liver injury.
    OBJECTIVE: To compare the therapeutic differences in liver fibrosis rats treated with transplantation of adipose-derived mesenchymal stem cells via caudal vein, portal vein and hepatic artery.
    METHODS: Seventy-five male Sprague-Dawley rats were selected, 15 of which were used as normal control without any intervention, and the remaining 60 rats were used to establish liver fibrosis models by subcutaneous injection of carbon tetrachloride. After modeling, these model rats were divided into four groups, in three groups of which, allogeneic adipose-derived mesenchymal stem cell suspension (2 mL, cell concentration of 1×109/L) was transplanted through hepatic artery, portal vein and caudal vein. The model group was injected with the same amount of cell culture medium via caudal vein. After 4 weeks of transplantation, liver function, liver fibrosis indexes and liver histopathology were detected and observed.
    RESULTS AND CONCLUSION: (1) Compared with the model group, the serum levels of alanine aminotransferase, alanine aminotransferase and total bilirubin were significantly reduced in the three transplantation groups (P < 0.05). Compared with the caudal vein transplantation group, the above indexes in and hepatic artery and portal vein transplantation groups were significantly lowered (P < 0.05). However, there was no difference between hepatic artery transplantation group and portal vein transplantation group. (2) Compared with the model group, the levels of hyaluronic acid, laminin and type III procollagen in liver tissues decreased significantly in the three cell transplantation groups (P < 0.05). Compared with the caudal vein transplantation group, the above indexes were significantly decreased in the hepatic artery transplantation group and portal vein transplantation group (P < 0.05). However, there was no difference in the above indexes between hepatic artery transplantation group and portal vein transplantation group. (3) Findings from hematoxylin-eosin staining and Masson staining showed typical pathological changes of liver fibrosis in the model group. Liver fibrosis was improved to different extents in the three transplantation groups as compared with the model group. The regression of liver fibrosis in hepatic artery transplantation group and portal vein transplantation group was better than that in caudal vein transplantation group. These findings indicate that adipose-derived mesenchymal stem cells transplanted via caudal vein, hepatic artery and portal vein can improve liver function and regress liver fibrosis in hepatic fibrosis rats. Moreover, cell transplantation via hepatic artery and portal vein is better than that via caudal vein.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Lingo-1 regulates neural stem cell differentiation via Rho-ROCK signaling pathway
    Peng Zhi-ming, Zhao Xiao-yang, Zhu Kai, Wan Yong
    2018, 22 (29):  4669-4674.  doi: 10.3969/j.issn.2095-4344.0625
    Abstract ( 333 )   PDF (860KB) ( 189 )   Save

    BACKGROUND: It has been reported that Lingo-1 plays an important role in neuronal axon regeneration and myelination, but whether it participates in the regulation of neural stem cell differentiation remains unknown.
    OBJECTIVE: To examine the effect of Lingo-1 knockdown on the differentiation of neural stem cells and to explore its potential mechanism.
    METHODS: Neural stem cells were isolated from neonatal rat brain tissue and identified by determination of several neural stem cell specific markers. Then the cells were transfected with Lingo-1 shRNA lentivirus or negative control vectors, and were further cultured in induced differentiation medium for 7 days. Immunofluorescence and western blot techniques were thereafter used to detect the expression of neuron specific markers and to examine expression levels of RhoA and ROCK1.
    RESULTS AND CONCLUSION: The cells isolated from brain tissue of neonatal rats aggregated to form non-adherent spherical clusters with high expression of Nestin, Sox2, and Pax6, specific markers of neural stem cells, which exhibited the characteristics of neural stem cells. After transfected with lentivirus, expression of Lingo-1 was successfully knocked down at mRNA and protein levels. After 7 days of induction, expression of neuron specific markers was significantly increased in Lingo-1 knocked-down neural stem cells. Meanwhile, expressions of RhoA and ROCK1 were decreased. Thus, Lingo-1 can be involved in the differentiation of neural stem cells. Inhibition of Lingo-1 can induce neural stem cells to differentiate into neurons, which is possibly related to the regulation of Rho-ROCK signaling pathway.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Effect of purmorphamine on neural stem cell differentiation and its mechanism
    Huang Zhi, Zhang Liang-ming, Chen Rui-qiang, Yang Yang, Yang Bu, Liu Chang, Chen Zhen-xiang, Liu Can,Rong Li-min, Liu Bin
    2018, 22 (29):  4675-4680.  doi: 10.3969/j.issn.2095-4344.0626
    Abstract ( 307 )   PDF (821KB) ( 204 )   Save

    BACKGROUND: The proliferation and differentiation of neural stem cells have always been a difficulty and a hot topic, which is of great significance to effectively increase the differentiation efficiency of neural stem cells into nerve cells. Recent reports have shown that purmorphamine, a small molecule compound, is widely used in various cell proliferation and differentiation experiments.
    OBJECTIVE: To investigate the role of purmorphamine in promoting the differentiation of neural stem cells into various types of nerve cells by up-regulating the Sonic Hedgehog(Shh) signaling pathway.
    METHODS: Primary neural stem cells were isolated from the hippocampus of mouse embryonic hippocampus. Cells at passages 2-4 were cultured in differentiation medium with purmorphamine (1 μmol/L; experimental group) or without purmorphamine (control group) for 7 and 14 days. The differentiation of neural stem cells was detected by immunocytochemistry and RT-qPCR.
    RESULTS AND CONCLUSION: Neural stem cells grew well in vitro, and most of the cells in the neurospheres expressed a specific marker of nestin. The cells cultured in the two groups were positive for TUJ1, GFAP, MAP2 and MBP. RT-qPCR results showed that the expression of TUJ1, GFAP, MAP2 and MBP in the experimental group was significantly higher than that in the control group at 7 days of culture (P < 0.05). The expression of Smo, Ptc1 and Gli-1 in the experimental group was significantly higher than that in the control group and the expression of GFAP, MAP2 and MBP was also significantly increased at 14 days of culture (P < 0.05). To conclude, purmorphmine can promote the differentiation of neural stem cells by up-regulating the Shh signaling pathway.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Transformation of human induced pluripotent stem cells into hepatocytes in 3D culture system
    Li Jia-jin, Wang Rong-li, Li Ting-ting, He Dong, Shi Wei
    2018, 22 (29):  4681-4686.  doi: 10.3969/j.issn.2095-4344.0627
    Abstract ( 336 )   PDF (754KB) ( 130 )   Save

    BACKGROUND: The construction of bioartificial liver is expected to be an effective method for the treatment of acute liver failure. However, there are still many problems in seed cell source, culture mode and nutrient acquisition, which restrict the development and clinical application of blood purification-artificial liver.
    OBJECTIVE: To investigate the feasibility of inducing the differentiation of induced pluripotent stem cells from human skin into hepatocyte-like cells without addition of exogenous sources such as exogenous serum.
    METHODS: A 3D culture system was constructed by using a three-dimensional culture system containing 6-well plates of the Transwell chamber. The induction and differentiation of human induced pluripotent stem cells were performed by addition of valproic acid and nicotinamide. The differentiated hepatocyte-like cells were co-cultured with biological patches. There were five groups in the experiment: human induced pluripotent stem cells were set as group A, normal hepatocytes as group B, hepatocyte-like cells without induction by nicotinamide as group C, hepatocyte-like cells with induction by nicotinamide as group D, and hepatocyte-like cells cultured on the biological patch as group E. The morphology of hepatocyte-like cells in group D was observed under inverted phase contrast microscope. The expression of nuclear factor 4α and alpha-fetoprotein in hepatocytes of group D was detected by immunofluorescence. Real-time quantitative PCR and western blot were used to detect mRNA and protein expressions of alpha-fetoprotein and albumin in the cells of groups A, B, C and D. Flow cytometry was used to detect the differentiation efficiency of cells in groups A, C and D. Immunocytochemistry detection was used to detect the protein expression of bile salt export pump in groups B and E. ELISA assay was used to detect lactate dehydrogenase activity, albumin and urea nitrogen contents in the supernatants of the groups D and E.
    RESULTS AND CONCLUSION: (1) The cells of group D changed from fusiform to polygon in shape. (2) Positive expression of hepatocyte nuclear factor 4 alpha and alpha fetoprotein was found in the cells of group D. (3) The gene and protein expressions of alpha fetoprotein and albumin in group D was significantly higher than those in groups A and C (P < 0.01). (4) The protein expression of bile salt export pump in the cells was remarkably positive in groups B and E. (4) The activity of lactate dehydrogenase and the contents of albumin and urea nitrogen in cultured cells of group E were significantly higher than those in group D (P < 0.01). To conclude, the combination of 3D culture system with exogenous small molecules and biological surgical patch helps to induce induced pluripotent stem cells to differentiate into functional hepatocyte-like cells in vitro.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Isolation and biological identification of tumor stem cells from ovarian cancer ID8 cell lines
    Yu Xiao-yu, Wu Di, Wang Jing, Li Fei, Bai Xu-le, Zhao Feng-shu, Dou Jun
    2018, 22 (29):  4687-4691.  doi: 10.3969/j.issn.2095-4344.0968
    Abstract ( 351 )   PDF (805KB) ( 200 )   Save

    BACKGROUND: Tumor stem cells play an important role in the initiation and development of tumor. However there is no report on whether tumor stem cells exist in mouse ovarian cancer cell line ID8.
    OBJECTIVE: To sort tumor stem-like cells from murine ID8 ovarian cancer cell line and to investigate its biological characteristics.
    METHODS: ID8 cells were cultured in the serum-free medium to derive tumor spheres. Cell counting kit 8, plate colony formation, Transwell assays and chemosensitivity testing were adopted to analyze the biological differences between suspending sphere cells and conventional cultured ID8 cells. Real-time PCR and western blot assays were performed to examine the expression of ALDH1. A mouse model of tumorigenicity was used to observe the tumorigenesis in vivo.
    RESULTS AND CONCLUSION: Ovarian ID8 cells grew into stable suspending tumor spheres in the serum-free medium. Compared with conventional ID8 cells, suspending sphere cells had stronger abilities of proliferation, self-renewal, invasion, drug resistance and tumorigenesis. Moreover, ALDH1 expression in suspending spheres cells was higher than that in conventional cultured ID8 cells. These findings indicate that serum-free medium culture can effectively enrich ID8 suspending sphere cells which have the properties of ovarian cancer stem cells.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Detection of minimal residual disease prior to allogeneic hematopoietic cell transplantation in middle-aged and elderly acute myeloid leukemia patients: a meta-analysis
    Feng You-fan, Wei Xiao-fang, Zhang Qi-ke
    2018, 22 (29):  4692-4697.  doi: 10.3969/j.issn.2095-4344.0628
    Abstract ( 392 )   PDF (594KB) ( 121 )   Save

    BACKGROUND: Residual leukemia cells still remain in the body of leukemia patients who are in complete remission at clinical and blood cytology levels. Therefore, minimal residual disease (MRD) is considered to be highly correlated with leukemia recurrence. Whether the MRD status affects the survival of patients after allogeneic hematopoietic stem cell transplantation remains the focus of controversy.
    OBJECTIVE: To evaluate the prognostic role of minimal residual disease (MRD) testing before allogeneic hematopoietic stem cell transplantation.
    METHODS: Published literature regarding MRD testing in middle-aged and elderly acute myeloid leukemia patients before allogeneic hematopoietic stem cell transplantation within CNKI, VIP Database, WanFang Database, PubMed, Embase, and the Cochrane Library were searched in this meta-analysis. Data were analyzed with the Stata 12.0 software package using pooled hazard ratios (HR) with 95% confidence intervals (CI).
    RESULTS AND CONCLUSION: A total of 8 studies involving 908 patients (227 positive for MRD and 681 negative for MRD) were included. The results of meta-analysis showed that pre-transplant MRD was associated with poor overall survival (HR=11.81, 95%CI: 4.76-29.31, P=0.000 1), disease-free survival (HR=10.75, 95%CI: 3.73-30.96, P=0.0001), cumulative incidence of relapse (HR=44.15, 95%CI: 13.20-147.69, P=0.000 1), and non-relapse mortality (HR=2.14, 95%CI: 1.48-3.10, P=0.001). To conclude, pre-transplant MRD (positive for MRD) may indicate poor prognosis in middle-aged and elderly acute myeloid leukemia patients. Therefore, a rational method to screen MRD is necessary prior to allogeneic hematopoietic stem cell transplantation.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    The roles of integrins and E-cadherin in the reprogramming and stemness maintenance of induced pluripotent stem cells
    Hu Ruo-wen, Chen Xiao-fang
    2018, 22 (29):  4698-4705.  doi: 10.3969/j.issn.2095-4344.0629
    Abstract ( 529 )   PDF (847KB) ( 154 )   Save

    BACKGROUND: Induced pluripotent stem cells (iPSCs) hold enormous potential as a tool to generate cells for disease modeling and regenerative medicine. The premise for clinical application of iPSCs is the efficient reprogramming of somatic cells to iPSCs. In recent years, increasing studies have demonstrated that integrins and E-cadherin play important roles in the reprogramming and maintenance of iPSCs. Investigations on the underlying molecular mechanism will help us developing safer and more efficient reprogramming methods for iPSCs generation and deeply understanding the reprogramming process.
    OBJECTIVE: To summarize the effect of integrins and E-cadherin on the reprogramming of iPSCs and the maintenance of pluripotency based on the insights into the underlying molecular mechanisms.
    METHODS: Scientific papers published from 2006 to present that described the effects of cell adhesion on reprogramming and stemness maintenance of iPSCs were retrieved by the first author in the Web of Science. Sixty-three articles related to the purpose of this review were reviewed.
    RESULTS AND CONCLUSION: Integrins-mediated cell-matrix adhesion and E-cadherin-mediated cell-cell adhesion can regulate pluripotent gene expression through a variety of downstream signaling pathways, and can also play important roles in the organization and contractility of actin cytoskeletons that generate gene-, protein-, and epigenetic-level changes and ultimately influence cell reprogramming and stemness maintenance.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Oxidized low-density lipoprotein can affect the function of endothelial progenitor cells: how to increase cell number and function?
    Wang Feng-jiao, Gao Xiang, Yin Hang, Chen Li, Qin Shu-cun, Yang Na-na
    2018, 22 (29):  4706-4712.  doi: 10.3969/j.issn.2095-4344.0630
    Abstract ( 336 )   PDF (693KB) ( 304 )   Save

    BACKGROUND: Various risk factors in atherosclerosis are closely related to the number and functions of endothelial progenitor cells (EPCs). Therefore, EPCs play an important role in the development of atherosclerosis, and increasing the number and functions of endothelial progenitor cells may be an important target for the treatment of atherosclerosis.
    OBJECTIVE: To elaborate the effect of oxidized low-density lipoprotein on EPCs functions.
    METHODS: PubMed and Chinese journal databases were searched by using “oxidized low-density lipoprotein, endothelial progenitor cells, atherosclerosis” as the search terms in English and Chinese, respectively. Finally, 42 articles were further analyzed.
    RESULTS AND CONCLUSION: Oxidized low-density lipoprotein, an important lipoprotein that induces atherosclerosis, can impair vascular endothelial cells to induce endothelial dysfunction, and contributes to foam cell formation and plaque stability. Oxidized low-density lipoprotein can damage the functions of EPCs, such as proliferation, migration, adhesion, angiogenesis, which reduces the effect of EPCs on vascular repair. Therefore, how to improve the number and functions of EPCs in atherosclerotic patients is an important target for the treatment of early atherosclerosis.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    CRISPR/Cas9: research advances in hematopoietic stem cell transplantation
    Yang Hui, Zhu Jian-wei, Lu Hui-li
    2018, 22 (29):  4713-4720.  doi: 10.3969/j.issn.2095-4344.0631
    Abstract ( 409 )   PDF (772KB) ( 189 )   Save

    BACKGROUND: The CRISPR/Cas9 gene editing system was derived from a bacterial adaptive system mediated by the Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and CRISPR-associated proteins (Cas). Hematopoietic stem cells (HSCs) are easy to isolate and capable of self-renewal and differentiation into different cell types, and have been successfully applied in the treatment of hematological malignancies and severe autoimmune diseases. In vivo and in vitro HSCs editing using the CRISPR/Cas9 system is a research trend that improves the therapeutic effect of HSCs transplantation, and has great clinical potential.
    OBJECTIVE: To review the disease therapeutics, delivery systems, gene editing and clinical application of CRISPR/Cas9 in HSCs transplantation.
    METHODS: The key words of “hematopoietic stem cells, CRISPR/Cas9, gene editing, delivery” in Chinese and English were used to search CNKI, PubMed and online databases respectively for relevant articles published from 2012 to 2018. After initial screening, the 61 eligible articles were further analyzed, summarized and concluded.
    RESULTS AND CONCLUSION: The simple and efficient gene editing ability of CRISPR/Cas9 can be applied to edit HSCs in vitro and in vivo and assist the clinical achievements of HSCs transplantation, which can reconstitute the life-long repair of hematopoietic system in the blood and immune systems in patients with hematopoiesis deficiencies. The limited delivery vehicles of CRISPR/Cas9 system remain to be further studied and optimized. In addition, the ethical and safety issues of CRISPR/Cas9 system in clinical research of HSCs need to be considered.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Premature senescence of mesenchymal stem cells: causes and preventive measures
    Zhou Long, He Fan, Wang Lei
    2018, 22 (29):  4721-4728.  doi: 10.3969/j.issn.2095-4344.0632
    Abstract ( 380 )   PDF (1519KB) ( 187 )   Save

    BACKGROUND: Mesenchymal stem cells (MSCs) have strong self-renewal and multi-directional differentiation potential, which have been widely applied in the tissue engineering and regenerative medicine. However, it is inevitable to face the aging of MSCs during in vitro amplification.
    OBJECTIVE: To elucidate the characteristics and causes of premature senescence of MSCs, and to summarize the measures to prevent the aging of MSCs in recent years, so as to explore a safe and effective method for early interventions that can delay the aging process.
    METHODS: A computer-based search of CNKI and PubMed was performed to retrieve relevant articles published from 1988 to 2017. The key words were “mesenchymal stem cells; senescence; prevent; bone tissue engineering” in Chinese and English, respectively. Totally 109 eligible were included in the result analysis.
    RESULTS AND CONCLUSION: Telomere shortening and oxidative stress make MSCs senescent. Growth factors, antioxidants, oxygen content and the extracellular matrix can significantly promote the proliferation of MSCs, and delay the cell aging. However, the specific mechanism is still unclear, which is worth further investigations.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Adipose-derived stem cells for treating knee osteoarthritis: relevant clinical trials and registration
    Pang Zhi-ying, Yin Feng, Yuan Feng
    2018, 22 (29):  4729-4735.  doi: 10.3969/j.issn.2095-4344.0633
    Abstract ( 521 )   PDF (749KB) ( 212 )   Save

    BACKGROUND: Osteoarthritis is the most common joint disease in elderly populations. Promising therapy that can control or even reverse the course of disease effectively remains unrevealed. Clinical trials focusing on applying adipose-derived stem cells for treating knee osteoarthritis have been conducted in the last few years, while the safety and viability remain unknown.
    OBJECTIVE: To summarize the completed and processing clinical trials in which adipose-derived stem cells are applied in treating knee osteoarthritis and to demonstrate the safety and efficiency.
    METHODS: PubMed, MEDLINE, Web of Science and Clinicaltrails.gov were searched for studies applying adipose-derived stem cells in the treatment of knee osteoarthritis up to December 2017. Inclusion criteria included randomized controlled trials, cohort studies and case series providing detailed study design, clinical data and follow-up results. Outcome measures included level of evidence, study design, inclusion criteria for patients, protocol for adipose-derived stem cells, clinical outcomes and serious adverse events.
    RESULTS AND CONCLUSION: Nine completed clinical trials (2 controlled studies, 2 dose-effect studies, 5 case series) were included. All studies reported a significant improvement after applying adipose-derived stem cells in pain management and joint function recovery and no serious adverse events were observed. These findings confirmed the effectiveness and safety of adipose-derived stem cells in the treatment of knee osteoarthritis, while these studies provided low-level evidence.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Bone marrow mesenchymal stem cells in the treatment of spinal cord injury: research hotspots and directions
    Lu Yu-bao, Yang Yang, Wang Yun-chang, Chen Guo-hu, Yuan Lin-hui, Li Chun-yan, Guan Xin, Ma Zhan-jun
    2018, 22 (29):  4736-4742.  doi: 10.3969/j.issn.2095-4344.0634
    Abstract ( 382 )   PDF (853KB) ( 187 )   Save

    BACKGROUND: As adult stem cells with multiple differentiation ability, bone marrow mesenchymal stem cells (BMSCs) have been proved to be effective in several studies on spinal cord injury, so it has gradually become a research hotspot in basic and clinical research. In addition, the technique of inducing the differentiation of BMSCs into neuron-like cells in various ways has been widely reported, which brings a new hope for the treatment of spinal cord injury by BMSCs transplantation. OBJECTIVE: To review the latest research of BMSCs concerning spinal cord injury treatment.
    METHODS: The relevant literatures published from January 2000 to December 2017 were retrieved in PubMed and CNKI. The keywords were “bone mesenchymal stem cells, spinal cord injury, transplantation” in English and Chinese, respectively. According to inclusion and exclusion criteria, 42 eligible articles were further analyzed.
    RESULTS AND CONCLUSION: Through the systematic comparative analysis, some problems concerning transplantation approaches, transplantation density, transplantation time, treatment efficiency and safety are encountered in the existing research regarding BMSCs transplantation for spinal cord injury. If relevant research has made breakthroughs in the above four aspects, it will bring new hope for nerve repair after spinal cord injury.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Stem cells for ophthalmic diseases: recovery from damage and functional reconstruction
    Zhou Li, Tian Bin, Ji Yuan-hong, Zhou Zheng, Wei Xiao-dan
    2018, 22 (29):  4743-4748.  doi: 10.3969/j.issn.2095-4344.0635
    Abstract ( 354 )   PDF (733KB) ( 202 )   Save

    BACKGROUND: With the in-depth research on stem cell repair and regeneration, stem cells have been accepted and become an issue of concern in the field of ophthalmology.
    OBJECTIVE: To review the animal and clinical research advances in the application of stem cells for the treatment of ophthalmic diseases.
    METHODS: The PubMed and CNKI databases were searched by the first author using the keywords of “stem cell, embryonic stem cell, ophthalmic diseases, limbal stem cell, adult stem cell” in English and Chinese, respectively. The retrieval time was from 1990 to 2017. After removal of repetitive or unrelated articles, 44 eligible articles were included in final analysis.
    RESULTS AND CONCLUSION: Stem cells are a specific cell group with self-renewing ability and multidirectional differentiation potential. It can be involved in the repair and reconstruction of damaged tissues. For the patients with serious injury or necrosis of the eye tissue and cells, stem cells as the core of regenerative medicine are used to repair the damaged eye tissue and cells and help to reconstruct visual functions. In China, the current research on stem cells in the field of ophthalmology is still in preclinical research stage. Considering the relevant data, we can conclude that stem cells have broad prospects in the treatment of ophthalmic diseases. 

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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    Basic research and clinical application of dental pulp stem cells: a bibliometric and visual analysis
    Yan Xue-chuan, Su Yu-cheng
    2018, 22 (29):  4749-4756.  doi: 10.3969/j.issn.2095-4344.0636
    Abstract ( 339 )   PDF (953KB) ( 152 )   Save

    BACKGROUND: Dental pulp stem cells have the advantages of abundant sources, convenient collection, and low immunogenicity, but no ethical dispute. Meanwhile, dental pulp stem cells have strong proliferative capacity, self-renewal ability and multi-directional differentiation potential, which have broad application prospects in pulp regeneration and dental restoration.
    OBJECTIVE: To conduct a statistical and visual analysis of literatures related to dental pulp stem cells.
    METHODS: The keyword of “dental pulp stem cells” in English and Chinese was used by the first author to retrieve relevant articles published from 2003 to 2018 in SCI, CNKI databases, Clinicaltrials.gov, and China patent database, respectively. These relevant literatures were statistically analyzed through the built-in analysis function and the drawing function of Excel software in terms of time distribution, country, regional distribution, organization 
    distribution, publication distribution and document type distribution.
    RESULTS AND CONCLUSION: The bibliometric and visual analysis for literatures addressing dental pulp stem cells published from 2003 to 2018 was performed by retrieval of the SCI, CNKI, Clinicaltrials.gov, and China patent database. This multi-aspect analysis on research trends in this field may provide valuable reference for relevant experts and researchers to further study hot topics in the field and select proper journals for paper submission.

    中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

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