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Neural Regeneration Research 2011年第19期6卷 1462-1466页

作者： Guangchun Ji Fei Song Qi Xing Jian Liu Kedong Song Daqing Zhang Zihan Wang The Second Affiliated Clinical College of Dalian Medical University Dalian 116023 Liaoning Province China The First Affiliated Clinical College of Dalian Medical University Dalian 116011 Liaoning Province China Institute of Chemical Engineering Dalian University of Technology/Dalian Stem Cell and Tissue Engineering Research and Development Center Dalian 116024 Liaoning Province China Dalian Central Hospital Dalian 116033 Liaoning Province China

This experiment sought to observe the migration and distribution of bone mesenchymal stem cells transfected with the cytosine deaminase gone （BMSCs-CD/eGFP） after transplantation in vivo through three pathways. In addition, we examined the tropism of these cells to glioma. Intracranial C6 glioma models were established in Sprague-Dawley rats using an intracranial stereotactic inoculation method. When tumors were 7 days old, rats were inoculated with lx106 BMSCs-CD/eGFP cells via the tumor-bearing internal carotid artery, the contralateral hemisphere and the tumor-bearing glioma. Fluorescence microscopy revealed that BMSCs-CD/eGFP exhibited a strong capacity for migration to tumors. BMSCs-CD/eGFP transplanted via the tumor-bearing intemal carotid artery were observed to distribute in glioma tissues. BMSCs-CD/eGFP inoculated via the ipsilateral glioma mainly located within and at the edge of glioma tissues. BMSCs-CD/eGFP inoculated via the contralateral hemisphere mainly distributed at the proximal end of the tumor at the incubation site.

关键词： cytosine deaminase gone bone mesenchymal stem cells glioma transduction migration

The Experimental Study on Constructing the Tissue Engineered Myocardium-like Tissue in vitro with bone mesenchymal stem cells

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Chinese Journal of Biomedical Engineering(English Edition) 2010年第1期19卷 8-15页

作者： XING Wan-hong MA Jie GUO Guang-wei LI Xin-hua XI Hu-yu Department of Cardiothoracic Surgery the Second Hospital of Shanxi Medical University Taiyuan 030001 China

Objective:Unlike other tissues,myocardium has not substitute whick can be used to repair damaged cardiac *** paper proposes engineering 3-D myocardium-like tissue constructs in vitro with bone mesenchymal stem cells(BMSCs) of infant and poly-lactic-co-glycolic acid(PLGA)in ***:bone marrow was obtained from the sternal marrow cavum outflow of infant with congenital heart disease (CHD)undergoing cardiac *** were obtained by density gradient *** cells in passages two were induced in DMED with 10 umol/L 5- Azacytidine(5-Aza)for 24 *** the induced BMSCS were cultured nearly into filled,the cells were planted in the scaffold of PLGA in 5.5×106 cells/*** cell- scaffold complex has been cultured in the shake cultivation for 1 week,then the complex has been planted in the dorse of the nude *** the experiment had been finished,the histology,immunology,real time PCR and so on were ***: The BMSCs of infant with congenital heart disease have the properties of the stable growth and the rapid *** immunohistochemistry showed that tissue engineered myocardium constructed in vitro expressed some cardiac related proteins such asα-actin,Cx-43,Desmine,cTNI and so *** transparent myofilaments,gap junctions and intercalated disk-like structure formation could be observed in the 3D tissue-like constructs by transmission electron microscope(TEM).The engineered myocardium-like tissue had the auto-myocardial property as assessed by real time- PCR and so ***:The engineered myocardial tissue-like constructs could be built with infant BMSCs and PLGA in *** results may provide the first step on the long road toward engineering myocardial material for repairing the defect or augmenting the tract in CHD,such as ventricular septal defect,tetralogy of Fallot and so on.

关键词： tissue engineering bone mesenchymal stem cells 5-Azacytidine myocardium in vitro

Effects of Stromal-derived Factor 1 Preconditioning on Apoptosis of Rat bone mesenchymal stem cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第4期29卷 423-426页

作者：陈军杜心灵张凯伦 Department of Cardiac Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and Technology

The effects of stromal-derived factor 1 preconditioning （PC） on apoptosis of bone mesenchymal stem cells （BMSCs） treated with hypoxia plus serum deprivation were investigated. bone mesenchymal stem cells were cultured with the whole marrow-adherence technique. RT-PCR and immunohistochemistry were used to detect the expression of CXCR4. BMSCs were incubated in medium for 24 h with 10 ng/mL and 100 ng/mL SDF-1 respectively, and then they were treated with hypoxia plus serum deprivation for 6 h. Apoptosis rate was determined by flow cytometry and TUNEL method. The results showed that BMSCs had CXCR4 expression. The number of apoptotic cells was significantly reduced in SDF-1 PC group as compared with the control group, and 100 ng/mL SDF-1 PC group had the lowest level of apoptosis. It was concluded that SDF-1 preconditioning suppresses the apoptosis of BMSCs treated with hypoxia plus serum deprivation.

关键词： bone mesenchymal stem cells SDF-1 preconditioning apoptosis

The study of migration of bone mesenchymal stem cells transplanted in intervertebral discs of rabbits and expression of exogenous gene

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Journal of Nanjing Medical University 2006年第5期20卷 287-291页

作者： Jintang Wang Hong Zhang Yingang Zhang Xiaowei Zhang Meng Li Department of Orthopaedics the First Affiliated Hospital Medical School Xi＇an Jiaotong University Xi＇an 710061China

Objective： To explore the survival and migration of bone mesenchymal stem cells transplantated in intervertebral disc of rabbits and expression of the exogenic genes. Methods. Thirty-two rabbits were used, A randomized block design was used and discs in the same rabbit were one block,the lumbar discs from L2-3 to L5-6 were randomly divided into blank group, saline group, cell transplantation group Ⅰand cell transplantation group Ⅱ. The fluorescence microscopy was used to determine the fluorescence of the maker protein GFP and DNA-PCR was used to analyze the copies of DNA of neomycin-resistant gene at 1, 3, 6, months after transplantation. Results： There was fluorescence in cell transplantation group Ⅰ and Ⅱ and none in blank group, saline group at 1, 3, 6 months after transplantation. In cell transplantation groups,the fluorescent distribution was more scatter with time, but no significant difference between cell groups Ⅰ and Ⅱ. The test of neomycin resistant gene expressed in cell transplantation group Ⅰ and Ⅱ and quantitative analysis showed that there was no significant difference between the cell groups Ⅰ and Ⅱ （P〉0.05）. Conclusion： The transplanted bone mesenchymal stem cells can survive, migrate and the transfer genes can express efficiently, it suggests that the BMSC therapy may be effective to prevent and treat intervertebral disc degeneration.

关键词： bone mesenchymal stem cells bone marrow cell stem cell transplant intervertebral disc Gene therapy

Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis:Implications for bone health

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World Journal of stem cells 2024年第4期16卷 389-409页

作者： Ling-Ling Wang Zhan-Jin Lu Shun-Kui Luo Yun Li Zhe Yang Hong-Yun Lu Department of Gerontology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Endocrinology and Metabolism The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Biomedical Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Endocrinology and Metabolism Zhuhai People’s Hospital(Zhuhai Clinical Medical College of Jinan Universitythe First Hospital Affiliated with Medical College of Macao University of Science and Technology)Zhuhai 519000Guangdong ProvinceChina

BACKGROUND Osteoporosis(OP)has become a major public health problem *** OP treatments are based on the inhibition of bone resorption,and it is necessary to identify additional treatments aimed at enhancing *** the bone marrow(BM)niche,bone mesenchymal stem cells(BMSCs)are exposed to a hypoxic ***,a few studies have demonstrated that hypoxiainducible factor 2alpha(HIF-2α)is involved in BMSC osteogenic differentiation,but the molecular mechanism involved has not been *** To investigate the effect of HIF-2αon the osteogenic and adipogenic differentiation of BMSCs and the hematopoietic function of hematopoietic stem cells(HSCs)in the BM niche on the progression of *** Mice with BMSC-specific HIF-2αknockout(Prx1-Cre;Hif-2αfl/fl mice)were used for in vivo *** quantification was performed on mice of two genotypes with three interventions:Bilateral ovariectomy,semilethal irradiation,and dexamethasone ***,the hematopoietic function of HSCs in the BM niche was compared between the two mouse *** vitro,the HIF-2αagonist roxadustat and the HIF-2αinhibitor PT2399 were used to investigate the function of HIF-2αin BMSC osteogenic and adipogenic ***,we investigated the effect of HIF-2αon BMSCs via treatment with the mechanistic target of rapamycin(mTOR)agonist MHY1485 and the mTOR inhibitor *** The quantitative index determined by microcomputed tomography indicated that the femoral bone density of Prx1-Cre;Hif-2αfl/fl mice was lower than that of Hif-2αfl/fl mice under the three intervention *** vitro,Hif-2αfl/fl mouse BMSCs were cultured and treated with the HIF-2αagonist roxadustat,and after 7 d of BMSC adipogenic differentiation,the oil red O staining intensity and mRNA expression levels of adipogenesis-related genes in BMSCs treated with roxadustat were decreased;in addition,after 14 d of osteogenic differentiation,BMSCs treated with roxadusta

关键词： Hypoxia-inducible factor-2α bone marrow niche bone mesenchymal stem cells Osteoporosis Osteogenic/adipogenic differentiation Mechanistic target of rapamycin signaling pathway

Exercise promotes osteogenic differentiation by activating the long non-coding RNA H19/microRNA-149 axis

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World Journal of Orthopedics 2024年第4期15卷 363-378页

作者： Xu-Chang Zhou Dong-Xue Wang Chun-Yu Zhang Ya-Jing Yang Ruo-Bing Zhao Sheng-Yao Liu Guo-Xin Ni School of Sport Medicine and Rehabilitation Beijing Sport UniversityBeijing 100084China Department of Acupuncture and Moxibustion Hubei University of Chinese MedicineWuhan 430065Hubei ProvinceChina Department of Spinal Surgery The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510260Guangdong ProvinceChina Department of Rehabilitation Medicine The First Affiliated Hospital of Xiamen UniversityXiamen 361003Fujian ProvinceChina

BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone *** To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying *** 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse *** analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic *** Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly *** micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of *** of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic *** addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by *** Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of *** lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

关键词： Exercise Osteogenic differentiation bone formation bone mesenchymal stem cells Autophagy

3D printed pore morphology mediates bone marrow stem cell behaviors via RhoA/ROCK2 signaling pathway for accelerating bone regeneration

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Bioactive Materials 2023年第8期26卷 413-424页

作者： Qiji Lu Jingjing Diao Yingqu Wang Jianlang Feng Fansen Zeng Yan Yang Yudi Kuang Naru Zhao Yingjun Wang School of Materials Science and Engineering South China University of TechnologyGuangzhou510641PR China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhou510006PR China NMPA Key Laboratory for Research and Evaluation of Innovative Biomaterials for Medical Devices.Guangzhou 510006PR China Medical Devices Research&Testing Center of SCUT Guangzhou510006PR China School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhou511442PR China Guangdong Institute of Advanced Biomaterials and Medical Devices Guangzhou510535PR China

bone bionics and structural engineering have sparked a broad interest in optimizing artificial scaffolds for better bone ***,the mechanism behind scaffold pore morphology-regulated bone regeneration remains unclear,making the structure design of scaffolds for bone repair *** address this issue,we have carefully assessed diverse cell behaviors of bone mesenchymal stem cells(BMSCs)on theβ-tricalcium phosphate(β-TCP)scaffolds with three representative pore morphologies(i.e.,cross column,diamond,and gyroid pore unit,respectively).Among the scaffolds,BMSCs on theβ-TCP scaffold with diamond pore unit(designated as D-scaffold)demonstrated enhanced cytoskeletal forces,elongated nucleus,faster cell mobility,and better osteogenic differentiation potential(for example,the alkaline phosphatase expression level in D-scaffold were 1.5-2 times higher than other groups).RNA-sequencing analysis and signaling pathway intervention revealed that Ras homolog gene family A(RhoA)/Rho-associated kinase-2(ROCK2)has in-depth participated in the pore morphology-mediated BMSCs behaviors,indicating an important role of mechanical signaling transduction in scaffold-cell ***,femoral condyle defect repair results showed that D-scaffold could effectively promote endogenous bone regeneration,of which the osteogenesis rate was 1.2-1.8 times higher than the other ***,this work provides insights into pore morphology-mediated bone regeneration mechanisms for developing novel bioadaptive scaffold designs.

关键词： bone mesenchymal stem cells 3D-printed scaffold Pore morphology bone regeneration Structure-osteogenesis relationship

Maternal inappropriate calcium intake aggravates dietary-induced obesity in male offspring by affecting the differentiation potential of mesenchymal stem cells

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World Journal of stem cells 2022年第10期14卷 756-776页

作者： Ping Li Yang Wang Pei Li Yuan-Lin Liu Wei-Jiang Liu Xiao-Yu Chen Tian-Tian Tang Ke-Min Qi Yi Zhang Laboratory of Nutrition and Development Key Laboratory of Major Diseases in Children's Ministry of EducationBeijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Experimental Hematology and Biochemistry Beijing Institute of Radiation MedicineBeijing 100085China Department of Pediatrics General Hospital of Tianjin Medical UniversityTianjin Medical UniversityTianjin 300070China

BACKGROUND The effects of inappropriate dietary calcium intake in early life on later obesity have not been fully *** To raise the mechanism of maternal calcium intake on the multi-differentiation potential of mesenchymal stem cells among their male *** Four-week-old female C57BL/6N mice were fed by deficient,low,normal and excessive calcium reproductive diets throughout pregnancy and *** MSCs(BMSCs)were obtained from 7-day-old male offspring to measure the adipogenic differentiation potential by the Wnt/β-catenin signaling *** other weaning male pups were fed a high-fat diet for 16 wk,along with normalfat diet as the *** the serum was collected for the measurement of biochemical ***,the adipose tissues were excised to analyze the adipocyte sizes and inflammatory *** the target gene expressions on the adipogenic differentiation and Wnt/β-catenin signaling pathway in the adipose tissues and BMSCs were determined by real-time reverse transcription polymerase chain *** Compared with the control group,maternal deficient,low and excessive calcium intake during pregnancy and lactation aggravated dietary-induced obesity,with larger adipocytes,more serious inflammatory infiltration and higher serum metabolism indicators by interfering with higher expressions of adipogenic differentiation(PPARγ,C/EBPα,Fabp4,LPL,Adiponectin,Resistin and/or Leptin)among their male offspring(P<0.05).And there were significantly different expression of similar specific genes in the BMSCs to successfully polarize adipogenic differentiation and suppress osteogenic differentiation in vivo and in vitro,respectively(P<0.05).Meanwhile,it was accompanied by more significant disorders on the expressions of Wnt/β-catenin signaling pathway both in BMSCs and adulthood adipose tissues among the offspring from maternal inappropriate dietary calcium intake *** Early-life abnormal dietary calcium intak

关键词： Calcium Obesity bone mesenchymal stem cells Wnt/β-catenin signaling pathway Adipogenic differentiation Male offspring

Differentiation of bone Marrow mesenchymal cells to Neural cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2005年第5期25卷 488-490,493页

作者：吴永超郑启新郭晓东谢宗平王运涛郝杰 Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China

Summary： To explore the possibility and condition of differentiation of bone marrow mesenchymal ceils （BMSCs） to neural ceils in vitro, BMSCs from whole bone marrow of rats were cultured. The BMSCs of passage 3 were identified with immunocytochemical staining of CD44 （＋）, CD71 （＋） and CD45（-）, There were type I and type H ceils in BMSCs. Type I BMSCs were spindlehaped and strong positive in immunocytochemical staining of CD44 and CD71, whereas flat and big type H BMSCs were lightly stained. The BMSCs of same passage were induced to differentiate into neural ceils by β-mercaptoethanol （BME）. After induction by BME, the type I BMSCs withdrew to form neuron-like round soma and axon-like and dendrite-like processes, and were stained positively for neurofilament （NF）. The type H BMSCs did not change in the BME medium and were negatively or slightly stained of NF.

关键词： bone mesenchymal stem cells cell differentiation neuron

Effects of the combined intervention of transplantation of bone marrow messchymal stem cell transfected with VEGF gene and Naomai Yi-hao capsule on the angiogenesis in cerebral ischemic rats

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Effects of the combined intervention of transplantation of b...