The application of appropriate cell origin for utilizing inregenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several st...The application of appropriate cell origin for utilizing inregenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells(ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage.展开更多
Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerv...Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerves,and blood vessels.Mesenchymal stromal cells(MSCs)take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans.Exosomes,which are among the key products MSCs release,mimic the effects of parental MSCs.They can shuttle various effector proteins,messenger RNA(mRNA)and microRNAs(miRNAs)to modulate the activity of recipient cells,playing important roles in wound healing.Moreover,using exosomes avoids many risks associated with cell transplantation.Therefore,as a novel type of cell-free therapy,MSC-exosome-mediated administration may be safer and more efficient than whole cell.In this review,we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration.In addition,we address the hypothesis of MSCs microenvironment extracellular vesicles(MSCs-MEVs)or MSCs microenvironment exosomes(MSCs-MExos)that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications.This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.展开更多
AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in...AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.展开更多
AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameter...AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters. METHODS: Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53. RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size. CONCLUSION: COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.展开更多
OBJECTIVE: To investigate the effect of icariin on proliferation of bone marrow mesenchymal stem cells(BMSCs) in Sprague-Dawley(SD) rats.METHODS: BMSCs were obtained from SD rat bone marrow with differential time adhe...OBJECTIVE: To investigate the effect of icariin on proliferation of bone marrow mesenchymal stem cells(BMSCs) in Sprague-Dawley(SD) rats.METHODS: BMSCs were obtained from SD rat bone marrow with differential time adherent method. Its characteristic was identified through differentiation cell surface antigens and the multi-lineage(osteo/adipo/chondo) differentiation potential. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) method and 5-Bromo-2-Deoxyuridine(Brd U) incorporation were applied to detect the effect of icariin on BMSCs proliferation.Flow cytometry was used to detect proliferation in-dex of BMSCs. The m RNA level and the distribution of β-catenin were evaluated by Real-time Polymerase Chain Reaction(PCR) and Immunofluorescent staining respectively. Western blot was used to detect protein expression levels of β-catenin, glycogen synthase kinase-3 beta(GSK-3β), phospho-glycogen synthase kinase-3 beta(p GSK-3β)and cyclin D1.RESULTS: Icariin promoted BMSCs proliferation at the concentration of 0.05-2.0 mg/L. The percentage of Brd U positive cells of BMSCs was increased from40.98% to 70.42%, and the proliferation index value was increased from 8.9% to 17.5% with the treatment of 0.05 mg/L icariin, which significance values were both less than 0.05. Compared with the control group, total and nuclear β-catenin proteins, as well as β-catenin m RNA expression, were all increased with icariin treatment. Meanwhile, the phosphorylation level of GSK-3β and cyclin D1 protein expressions were also increased in BMSCs with icariin treatment.CONCLUSION: The findings of the present study demonstrated that low dosage of icariin could promote BMSCs proliferation. The activation of Wnt/β-catenin pathways was involved in this process.展开更多
Background： Fat grafting technologies are popularly used in plastic and reconstructive surgery. Due to its size limitation, it is hard to directly inject untreated iht tissue into the dermal layer. Nanolht, which was...Background： Fat grafting technologies are popularly used in plastic and reconstructive surgery. Due to its size limitation, it is hard to directly inject untreated iht tissue into the dermal layer. Nanolht, which was introduced by Tonnard, solves this problem by mechanically emulsifying fat tissue. However, the viability of the cells was greatly destroyed. In this study, we reported a new method by ＂gently＂ digesting the fat tissue to produce viable adipocytes, progenitors, and stromal stem cells using collagenase I digestion and centrifugation. This was named ＂Vivo nanofat＂. Methods： Human liposuction aspirates were obtained from five healthy female donors with mean age of 28.7±5.6 years. Colony-forming assay, flow cytometry analysis, and adipogenic and osteogenic induction of the adherent cells from the Vivo nanofat were used to characterize the adipose mesenchymal stem cells （MSCs）. To investigate in vivo survival, we respectively injected Vivo nanofat and nanofat subcutaneously to the back of 8-week-old male BALB/c nude mice. Samples were harvested 2 days, 2 weeks, and 4 weeks postiniection for measurement, hematoxylin and eosin staining, and immunostaining. Results： Our results showed that the Vivo nanofat contained a large number ofcolony-fbrming cells. These cells expressed MSC markers and had multi-differentiative potential. In vivo transplantation showed that the Vivo nanofat had lower resorption ratio than that of nanofat. The size of the transplanted nanofat was obviously smaller than that of Vivo nanofat 4 weeks postinjection （0.50±0.17 cm vs. 0.81 ± 0.07 cm, t = -5783, P- 0.01）. Conclusion： Vivo nanofat may serve as a cell fraction injectable through a fine needle; this could be used for cosmetic applications.展开更多
BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that me...BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.展开更多
AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor an...AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumoradjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (chi(2) = 6.669, P = 0.010; chi(2) = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.展开更多
Background: Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats v...Background: Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF). Methods: An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (w = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4;SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis. Results: HBO treatment recovered SCI-induced descent of BBB scores on POD 14,(1.25±0.75 vs. 1.03 ±0.66, P< 0.05), 21 (5.27± 0.89 vs. 2.56± 1.24, P< 0.05), and 28 (11.35±0.56 vs. 4.23± 1.20, P<0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89± 1.60 vs. 1.56±0.98, P<0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99± 1.60 vs. 1.31 ±0.98, P<0.05;day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18± 1.60 vs. 0.80±0.34, P<0.05;day 21, SCI + HBO vs. SCI, 2.10±1.01 vs.1.15±0.03, P<0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04±0.41 vs. 2.75±0.31, P<0.05;day 14, SCI + HBO vs. SCI, 3.88± 1.59 vs. 1.11 ±0.40, P<0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO. Conclusions: HBO might promote the recovery of neurologic func展开更多
文摘The application of appropriate cell origin for utilizing inregenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells(ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage.
基金funded by National Natural Science Foundation of China(81871570,81560313).
文摘Cutaneous regeneration at the wound site involves several intricate and dynamic processes which require a series of coordinated interactions implicating various cell types,growth factors,extracellular matrix(ECM),nerves,and blood vessels.Mesenchymal stromal cells(MSCs)take part in all the skin wound healing stages playing active and beneficial roles in animal models and humans.Exosomes,which are among the key products MSCs release,mimic the effects of parental MSCs.They can shuttle various effector proteins,messenger RNA(mRNA)and microRNAs(miRNAs)to modulate the activity of recipient cells,playing important roles in wound healing.Moreover,using exosomes avoids many risks associated with cell transplantation.Therefore,as a novel type of cell-free therapy,MSC-exosome-mediated administration may be safer and more efficient than whole cell.In this review,we provide a comprehensive understanding of the latest studies and observations on the role of MSC-exosome therapy in wound healing and cutaneous regeneration.In addition,we address the hypothesis of MSCs microenvironment extracellular vesicles(MSCs-MEVs)or MSCs microenvironment exosomes(MSCs-MExos)that need to take stock of and solved urgently in the related research about MSC-exosomes therapeutic applications.This review can inspire investigators to explore new research directions of MSC-exosome therapy in cutaneous repair and regeneration.
基金Supported by The National Natural Science Foundation of China, No. 30772542
文摘AIM:To investigate the role of CXC chemokine receptor-4 (CXCR4) and stromal cell-derived factor-1 (SDF-1) in lymph node metastasis of gastric carcinoma.METHODS:In 40 cases of gastric cancer,expression of CXCR4 mRNA in cancer and normal mucous membrane and SDF-1 mRNA in lymph nodes around the stomach was detected using quantitative polymerase chain reaction (PCR) (TaqMan) and immunohistochemistric assay.SGC-7901 and MGC80-3 cancer cells were used to investigate the effect of SDF-1 on cell proliferation and migration.RESULTS:Quantitative reverse transcription PCR and immunohistochemistry revealed that the expression level of CXCR4 in gastric cancer was significantly higher than that in normal mucous membrane (1.6244 ± 1.3801 vs 1.0715 ± 0.5243,P < 0.05).The expression level of CXCR4 mRNA in gastric cancer with lymph node metastasis was also significantly higher than that without lymph node metastasis (0.823 ± 0.551 vs 0.392 ± 0.338,P < 0.05).CXCR4 expression was significantly related to poorly differentiated,high tumor stage and lymph node metastasis.Significant differences in the expression level of SDF-1 mRNA were found between lymph nodes in metastatic gastric cancer and normal nodes (0.5432 ± 0.4907 vs 0.2640 ± 0.2601,P < 0.05).The positive expression of SDF-1 mRNA in lymph nodes of metastatic gastric cancer was consistent with the positive expression of CXCR4 mRNA in gastric cancer (r=0.776,P < 0.01).Additionally,human gastric cancer cell lines expressed CXCR4 and showed vigorous proliferation and migratory responses to SDF-1.AMD3100 (a specific CXCR4 antagonist) was also found to effectively reduce the migration of gastric cancer cells.CONCLUSION:The CXCR4/SDF-1 axis is involved in the lymph node metastasis of gastric cancer.CXCR4 is considered as a potential therapeutic target in the treatment of gastric cancer.
文摘AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters. METHODS: Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2, PCNA, Ki-67 and p53. RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI, tumor grade and tumor size. CONCLUSION: COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.
基金the the National Natural Science Foundation of China(Study on the Bushen Chinese Medicine on the BMSCs Differentiation,No.81173619,81403479)Natural Science Foundation of the Jiangsu Province of China(Study of Acupuncture on Ischemic Stroke,No.BK20130956)Specialized Research Fund for the Doctoral Program of Higher Education of China(Epigenetic Mechanism of Acupuncture on Brain Injury,No.20133237120002)
文摘OBJECTIVE: To investigate the effect of icariin on proliferation of bone marrow mesenchymal stem cells(BMSCs) in Sprague-Dawley(SD) rats.METHODS: BMSCs were obtained from SD rat bone marrow with differential time adherent method. Its characteristic was identified through differentiation cell surface antigens and the multi-lineage(osteo/adipo/chondo) differentiation potential. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) method and 5-Bromo-2-Deoxyuridine(Brd U) incorporation were applied to detect the effect of icariin on BMSCs proliferation.Flow cytometry was used to detect proliferation in-dex of BMSCs. The m RNA level and the distribution of β-catenin were evaluated by Real-time Polymerase Chain Reaction(PCR) and Immunofluorescent staining respectively. Western blot was used to detect protein expression levels of β-catenin, glycogen synthase kinase-3 beta(GSK-3β), phospho-glycogen synthase kinase-3 beta(p GSK-3β)and cyclin D1.RESULTS: Icariin promoted BMSCs proliferation at the concentration of 0.05-2.0 mg/L. The percentage of Brd U positive cells of BMSCs was increased from40.98% to 70.42%, and the proliferation index value was increased from 8.9% to 17.5% with the treatment of 0.05 mg/L icariin, which significance values were both less than 0.05. Compared with the control group, total and nuclear β-catenin proteins, as well as β-catenin m RNA expression, were all increased with icariin treatment. Meanwhile, the phosphorylation level of GSK-3β and cyclin D1 protein expressions were also increased in BMSCs with icariin treatment.CONCLUSION: The findings of the present study demonstrated that low dosage of icariin could promote BMSCs proliferation. The activation of Wnt/β-catenin pathways was involved in this process.
文摘Background： Fat grafting technologies are popularly used in plastic and reconstructive surgery. Due to its size limitation, it is hard to directly inject untreated iht tissue into the dermal layer. Nanolht, which was introduced by Tonnard, solves this problem by mechanically emulsifying fat tissue. However, the viability of the cells was greatly destroyed. In this study, we reported a new method by ＂gently＂ digesting the fat tissue to produce viable adipocytes, progenitors, and stromal stem cells using collagenase I digestion and centrifugation. This was named ＂Vivo nanofat＂. Methods： Human liposuction aspirates were obtained from five healthy female donors with mean age of 28.7±5.6 years. Colony-forming assay, flow cytometry analysis, and adipogenic and osteogenic induction of the adherent cells from the Vivo nanofat were used to characterize the adipose mesenchymal stem cells （MSCs）. To investigate in vivo survival, we respectively injected Vivo nanofat and nanofat subcutaneously to the back of 8-week-old male BALB/c nude mice. Samples were harvested 2 days, 2 weeks, and 4 weeks postiniection for measurement, hematoxylin and eosin staining, and immunostaining. Results： Our results showed that the Vivo nanofat contained a large number ofcolony-fbrming cells. These cells expressed MSC markers and had multi-differentiative potential. In vivo transplantation showed that the Vivo nanofat had lower resorption ratio than that of nanofat. The size of the transplanted nanofat was obviously smaller than that of Vivo nanofat 4 weeks postinjection （0.50±0.17 cm vs. 0.81 ± 0.07 cm, t = -5783, P- 0.01）. Conclusion： Vivo nanofat may serve as a cell fraction injectable through a fine needle; this could be used for cosmetic applications.
基金Supported by the National Key Research and Development Program,No.2018YFC1002105the Key Research and Development Program of Liaoning Province,No.2018020222the Major Special Construction Plan for Discipline Construction Project of China Medical University,No.3110118033。
文摘BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.
基金Supported by the Tianjin Binhai New Area Health Industry Medical and Health Science Project,No.2011BHKY021Tianjin Binhai New Area Science and Technology Development Strategy Research Project,No.2012DK15W007Tianjin Binhai New Area Port Area Social Development Science and Technology Project,No.20120211
文摘AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumoradjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (chi(2) = 6.669, P = 0.010; chi(2) = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.
文摘Background: Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF). Methods: An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (w = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4;SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis. Results: HBO treatment recovered SCI-induced descent of BBB scores on POD 14,(1.25±0.75 vs. 1.03 ±0.66, P< 0.05), 21 (5.27± 0.89 vs. 2.56± 1.24, P< 0.05), and 28 (11.35±0.56 vs. 4.23± 1.20, P<0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89± 1.60 vs. 1.56±0.98, P<0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99± 1.60 vs. 1.31 ±0.98, P<0.05;day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18± 1.60 vs. 0.80±0.34, P<0.05;day 21, SCI + HBO vs. SCI, 2.10±1.01 vs.1.15±0.03, P<0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04±0.41 vs. 2.75±0.31, P<0.05;day 14, SCI + HBO vs. SCI, 3.88± 1.59 vs. 1.11 ±0.40, P<0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO. Conclusions: HBO might promote the recovery of neurologic func
