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Hepatocyte Growth Factor Gene-modified Bone Marrow-derived mesenchymal stem cells Transplantation Promotes Angiogenesis in a Rat Model of Hindlimb Ischemia

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第4期33卷 511-519页

作者：苏冠华孙雨霏卢永昕帅欣欣廖玉华刘启云韩俊罗平 Department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Cardiology Wuhan Pu'ai HospitalTongji Medical CollegeHuazhong University of Science and Technology

Summary： Angiogenic gene therapy and cell-based therapy for peripheral arterial disease （PAD） have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells （MSCs）transplantation with ex vivo human hepatocyte growth factor （HGF） gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley （SD） rats were randomized to receive HGF gene-modified MSCs transplantation （HGF-MSC group）, untreated MSCs transplantation （MSC group）, or PBS injection （PBS group）, respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.

关键词： angiogenesis gene therapy hepatocyte growth factor mesenchymal stem cell peripheralarterial disease

Human hair follicle-derived mesenchymal stem cells:Isolation,expansion,and differentiation

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World Journal of stem cells 2020年第6期12卷 462-470页

作者： Bo Wang Xiao-Mei Liu Zi-Nan Liu Yuan Wang Xing Han Ao-Bo Lian Ying Mu Ming-Hua Jin Jin-Yu Liu Department of Toxicology School of Public HealthJilin UniversityChangchun 130021Jilin ProvinceChina Research Center for Analytical Instrumentation Institute of Cyber-Systems and ControlState Key Laboratory of Industrial Control TechnologyZhejiang UniversityHangzhou 310000Zhejiang ProvinceChina

Hair follicles are easily accessible skin appendages that protect against cold and potential *** follicles contain various pools of stem cells,such as epithelial,melanocyte,and mesenchymal stem cells(MSCs)that continuously self-renew,differentiate,regulate hair growth,and maintain skin ***,MSCs derived from the dermal papilla or dermal sheath of the human hair follicle have received attention because of their accessibility and broad differentiation *** this review,we describe the applications of human hair follicle-derived MSCs(hHF-MSCs)in tissue engineering and regenerative *** have described protocols for isolating hHF-MSCs from human hair follicles and their culture condition in *** also summarize strategies for maintaining hHF-MSCs in a highly proliferative but undifferentiated state after repeated in vitro passages,including supplementation of growth factors,3D suspension culture technology,and 3D aggregates of *** addition,we report the potential of hHF-MSCs in obtaining induced smooth muscle cells and tissue-engineered blood vessels,regenerated hair follicles,induced red blood cells,and induced pluripotent stem *** summary,the abundance,convenient accessibility,and broad differentiation potential make hHF-MSCs an ideal seed cell source of regenerative medical and cell therapy.

关键词： Human hair follicle Regenerative therapy mesenchymal stem cell Tissue engineering cell differentiation

Altered physiology of mesenchymal stem cells in the pathogenesis of adolescent idiopathic scoliosis

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World Journal of Clinical Cases 2020年第11期8卷 2102-2110页

作者： Dai Sik Ko Yun Hak Kim Tae Sik Goh Jung Sub Lee Division of Vascular Surgery Department of SurgeryGachon University Gil Medical CenterIncheoz 21565South Korea Department of Anatomy and Department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612South Korea Department of Orthopaedic Surgery and Biomedical Research Institute Pusan National University HospitalBusan 49241South Korea

Adolescent idiopathic scoliosis is the most common spinal deformity during puberty,especially in *** is characterized by aberrant skeletal growth and generalized reduced bone density,which is associated with impaired bone mineral *** recent progress in multidisciplinary research to support various hypotheses,the pathogenesis of Adolescent idiopathic scoliosis is still not clearly *** of the hypothesis is to study the role of mesenchymal stem cells due to its involvement in the above-mentioned bone metabolic *** this review,we will summarize reported literatures on the role of mesenchymal stem cells,particularly in the pathogenesis of Adolescent idiopathic *** addition,we will describe the research on mesenchymal stem cells of Adolescent idiopathic scoliosis performed using bioinformatics tools.

关键词： Adolescent idiopathic scoliosis mesenchymal stem cell Bioinformatics Transcriptome Proteome

Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion

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World Journal of stem cells 2021年第2期13卷 177-192页

作者： Hua-Su Zhu Dong Li Cong Li Jin-Xian Huang Shan-Shan Chen Lan-Bo Li Qing Shi Xiu-Li Ju Department of Pediatrics Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina stem cell and Regenerative Medicine Research Center Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Department of Animal Laboratory Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Department of Pediatrics Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system *** clinical treatments for MS are *** evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune *** the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive *** To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of *** A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs *** Morris water maze(MWM)test was used to observe the symptom of ***-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone *** blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear *** examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone *** The MWM test demonstrated that UC-MSCs improved the symptoms of *** MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that

关键词： mesenchymal stem cell Motion sickness Inflammation Immune microenvironment Interleukin-10 JAK2/STAT3

Prospects for the therapeutic development of umbilical cord bloodderived mesenchymal stem cells

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World Journal of stem cells 2020年第12期12卷 1511-1528页

作者： Soyoun Um Jueun Ha Soo Jin Choi Wonil Oh Hye Jin Jin Research Team for Immune cell Therapy Biomedical Research InstituteMEDIPOST Co.Ltd.Seongnam 13494South Korea Research Team for Osteoarthritis Biomedical Research InstituteMEDIPOST Co.Ltd.Seongnam 13494South Korea Biomedical Research Institute MEDIPOST Co.Ltd.Seongnam 13494South Korea

Umbilical cord blood(UCB)is a primitive and abundant source of mesenchymal stem cells(MSCs).UCB-derived MSCs have a broad and efficient therapeutic capacity to treat various diseases and *** the high latent selfrenewal and differentiation capacity of these cells,the safety,efficacy,and yield of MSCs expanded for ex vivo clinical applications remains a ***,immunomodulatory effects have emerged in various disease models,exhibiting specific mechanisms of action,such as cell migration and homing,angiogenesis,anti-apoptosis,proliferation,anti-cancer,anti-fibrosis,anti-inflammation and tissue ***,we review the current literature pertaining to the UCB-derived MSC application as potential treatment strategies,and discuss the concerns regarding the safety and mass production issues in future applications.

关键词： Umbilical cord blood mesenchymal stem cell stem cell therapy Immunomodulation Regenerative medicine Therapeutic cell manufacturing processing

Biological, chemical and mechanical factors regulating migration and homing of mesenchymal stem cells

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World Journal of stem cells 2021年第6期13卷 619-631页

作者： Renata Szydlak Department of Medical Biochemistry Faculty of MedicineJagiellonian University Medical CollegeKraków 31-034Poland

mesenchymal stem cells(MSCs)are a population of primary and non-specialized cells,which can be isolated from various ***,MSCs are key players in cellular therapy and regenerative ***,the possibility of using MSCs in the treatment of many diseases needs to be preceded,though,by indepth analysis of their properties,especially by determining the mechanism of tissue homing as well as the mechanism,due to which cells contribute to tissue *** review is intended to present information on recent findings regarding the mechanism of recruitment and tissue homing by MSCs and discuss current hypotheses for how MSCs can reach target tissues.

关键词： mesenchymal stem cell cell migration Regenerative medicine mesenchymal stem cell-based therapy

Fish scale-derived scaffolds with MSCs loading for photothermal therapy of bone defect

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Nano Research 2023年第5期16卷 7383-7392页

作者： Siyu Shen Rui Liu Chuanhui Song Tao Shen Yiwen Zhou Junxia Guo Bin Kong Qing Jiang State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China The Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008China Department of Orthodontics Nanjing Stomatological HospitalMedical School of Nanjing UniversityNanjing 210008China Department of Sports Medicine and Adult Reconstructive Surgery Nanjing Drum Tower HospitalClinical College of Nanjing Medical UniversityNanjing 210008China Department of Biomedical Engineering School of MedicineShenzhen UniversityShenzhen 518060China

Tissue engineering scaffolds have presented effective value in bone ***,the integration of the diverse components,complex structures,multifunction to impart the scaffolds with improved applicability is still a ***,we propose a novel fish-derived scaffold combined with photothermal therapy and mesenchymal stem cells(MSCs)to promote bone *** fish-derived scaffold is composed of the decellularized fish scale and gelatin methacrylate synthesized from fish gelatin(fGelMA),which can promote the proliferation and osteogenesis of MSCs with no obvious immunological ***,the black phosphorus(BP)nanosheets are incorporated into the fGelMA hydrogel network,which can endow the hydrogel with the capacity of photothermal conversion stimulated by near-infrared(NIR)*** fish-derived scaffold can promote the osteogenesis process of MSCs with higher expression of osteogenic markers and higher mineralization assisted by the NIR light in *** regeneration of mice calvarial defect has also been accelerated by the scaffold with photothermal therapy and *** results suggest that the fish-derived scaffold,photothermal therapy,MSCs-based regenerative therapy is a promising clinical strategy in bone regeneration.

关键词： fish scale GelMA photothermal therapy mesenchymal stem cell bone regeneration

Differentiation of GDNF and NT-3 Dual Gene-modified Rat Bone Marrow mesenchymal stem cells into Enteric Neuron-like cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第1期32卷 87-91页

作者：高贺云魏明发王燕吴晓娟朱天琦 Department of Pediatric Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Otorhinolaryngology Head and Neck Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

Bone marrow mesenchymal stem cells (BMSCs) have been shown to be multipotent cells that possess high self-replicating *** purpose of our study was to investigate the feasibility of using enteric neuron-like cells obtained by in vitro induction and differentiated from rat BMSCs for the treatment of Hirschsprung’s disease (HD).Glial cell-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) are neurotrophic factors that play important roles in neuronal development,differentiation,survival and ***,GDNF mutations are a major cause of *** this study,BMSCs were transfected with eukaryotic expression plasmids co-expressing GDNF and NT-3,and the trans-fected cells displayed neuron-like changes after differentiation induced by fetal gut culture medium (FGCM).Immunofluorescence assay showed positive expression of the neuronal marker NSE and the enteric neuronal markers PGP9.5,VIP and *** transcription-polymerase chain reaction (RT-PCR) revealed the expression of GDNF and NT-3 in transfected *** present study indicates that genetically modified BMSCs coexpressing GDNF and NT-3 are able to differentiate into en-teric neuronal cells and express enteric nerve markers when induced by *** study provides an experimental basis for gene therapy to treat enteric nervous system-related disorders,such as HD.

关键词： mesenchymal stem cell glial cell-derived neurotrophic factor neurotrophin-3 enteric neu-rons cell transfection

Effect of RGD-modified Silk Material on the Adhesion and Proliferation of Bone Marrow-derived mesenchymal stem cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第1期29卷 80-83页

作者：王洪马亮杨述华邵增务孟春庆段德宇李艳军 Department of Orthopedics Union Hospital Tongji Medical College Huazhong University of Science and Technology

In order to investigate the effect ofArg-Gly-Asp （RGD） peptide-modified silk biomaterial on the adhesion and proliferation of bone marrow-derived mesenchymal stem cells （MSCs）, MSCs of third generation were seeded onto the surface of RGD-decorated silk （silk-RGD group）, silk alone （silk group） or tissue culture plate （TCP group）. After incubation for 4 or 12 h, MSCs were examined quantitatively by using precipitation method for cell attachment. The cell proliferation, which was defined as cell density, was compared among the three groups after culture for 1, 2, 3, and 4 days. cell skeleton, which was labeled fluorescently, was observed under laser confocal microscope after 24 h of culture. The results showed that cell adhesion rate in silk-RGD group was higher than in silk group （P〈0.05）, but similar to that in TCP group after incubation for 4 or 12 h （P〉0.05）. There were no sig- nificant differences in the cell proliferation among the three groups at different time points （P〉0.05 for all）. Laser confocal microscopy revealed that in silk-RGD group, MSCs, strongly fluorescently stained, spread fully, with stress fibers clearly seen, while in silk group, actin filaments were sparsely aligned and less stress fibers were found. It was concluded that RGD peptide could improve the ad- hesion of MSCs to the silk scaffold, but had no impact on the proliferation of the cells.

关键词： RGD peptide silk scaffold mesenchymal stem cell adhesion proliferation