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human umbilical cord mesenchymal stem cells derived from Wharton＇s jelly differentiate into insulin-producing cells in vitro

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Chinese Medical Journal 2011年第10期000卷 1534-1539页

作者： WANG Hong-wu LIN Li-min HE Hong-yan YOU Fang LI Wei-zhong HUANG Tian-hua MA Gui-xia MA Lian Department of Pediatrics Second Affiliated Hospital of Shantou University Medical College Shantou Guangdong 515041 China Department of Surgery First Affiliated Hospital of Shantou University Medical College Shantou Guangdong 515041 China Research Center for Reproductive Medicine Shantou University Medical College Shantou Guangdong 515041 China

Background Islet transplantation is an effective way of reversing type Ⅰ diabetes. However, islet transplantation is hampered by issues such as immune rejection and shortage of donor islets. Mesenchymal stem cells can differentiate into insulin-producing cells. However, the potential of human umbilical cord mesenchymal stem cells （huMSCs） to become insulin-producing cells remains *** We isolated and induced cultured huMSCs under islet cell culture conditions. The response of huMSCs were monitored under an inverted phase contrast microscope. Immunocytochemical and immunofluorescence staining methods were used to measure insulin and glucagon protein levels. Reverse transcription-polymerase chain reaction （RT-PCR） was performed to detect gene expression of human insulin and PDX-1. Dithizone-staining was employed to determine the zinc contents in huMSCs. Insulin secretion was also evaluated through *** HuMSCs induced by nicotinamide and β-mercaptoethanol or by neurogenic differentiation 1 gene （NeuroD1）transfection gradually changed morphology from typically elongated fibroblast-shaped cells to round cells. They had a tendency to form clusters. Immunocytochemical studies showed positive expression of human insulin and glucagon in these cells in response to induction. RT-PCR experiments found that huMSCs expressed insulin and PDX-1 genes following induction and dithizone stained the cytoplasm of huMSCs a brownish red color after induction. Insulin secretion in induced huMSCs was significantly elevated compared with the control group （t=6.183, P〈0.05）.Conclusions HuMSCs are able to differentiate into insulin-producing cells in vitro. The potential use of huMSCs in βcell replacement therapy of diabetes needs to be studied further

关键词： human umbilical cord mesenchymal stem cells differentiation insulin-producing cells

Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

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International Journal of Ophthalmology(English edition) 2016年第1期9卷 41-47页

作者： Song Chen Wei Zhang Ji-Ming Wang Hong-Tao Duan Jia-Hui Kong Yue-Xin Wang Meng Dong Xue Bi Jian Song Tianjin Eye Hospital Tianjin Key Lab of Ophthalmology and Visual Science Tianjin Eye Institute Clinical College of Ophthalmology Tianjin Medical University

AIM：To investigate whether umbilical cord human mesenchymal stem cell（UC-MSC）was able to differentiate into neural stem cell and neuron.·METHODS：The umbilical cords were o btained from pregnant women with their written consent and the approval of the Clinic Ethnics ***-MSC were isolated by adherent culture in the medium contains 20%fetal bovine serum（FBS）,then they were maintained in the medium contain 10%FBS and induced to neural cells in neural differentiation *** investigated whether UC-MSC was able to differentiate into neural stem cell and neuron by using flow cytometry,reverse transcriptase-polymerase chain reaction（RT-PCR）and immunofluorescence（IF）analyzes.·R ESULTS：A substantial number of UC-MSC was harvested using the tissue explants adherent method at about *** cytometric study revealed that these cells expressed common markers of MSCs,such as CD105（SH2）,CD73（SH3）and *** induction of differentiation of neural stem cells,the cells began to form clusters;RT-PCR and IF showed that the neuron specific enolase（NSE）and neurogenic differentiation 1-positive cells reached 87.3%±14.7%and 72.6%±11.8%,*** showed neuronal cell differentiation after induced,including neuron-like protrusions,plump cell body,obviously and stronger ***-PCR and IF analysis showed that microtubule-associated protein 2（MAP2）and nuclear factor-M-positive cells reached 43.1%±10.3%and 69.4%±19.5%,respectively.·CONCLUSION：human umbilical cord derived MSCs can be cultured and proliferated and differentiate into neural stem cells,which may be a valuable source for cell therapy of neurodegenerative eye diseases.

关键词： human umbilical cord mesenchymal stemcells neural stem cells neuron neurodegenerative eye diseases

Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

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World Journal of Stem Cells 2024年第2期16卷 70-88页

作者： Min Meng Wei-Wei Zhang Shuang-Feng Chen Da-Rui Wang Chang-Hui Zhou Department of Central Laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina Department of Clinical Laboratory Liaocheng People’s HospitalLiaocheng 252000Shandong ProvinceChina

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues *** diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung *** umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage ***,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung *** searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary *** this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical ***,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in *** brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

关键词： Pulmonary diseases Mesenchymal stem cells human umbilical cord Cell therapy Clinical trials

Zinc enhances the cell adhesion,migration,and self-renewal potential of human umbilical cord derived mesenchymal stem cells

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World Journal of Stem Cells 2023年第7期15卷 751-767页

作者： Iqra Sahibdad Shumaila Khalid G Rasul Chaudhry Asmat Salim Sumreen Begum Irfan Khan Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Department of Biological Sciences Oakland UniversityRochesterMI 48309United States Stem Cell Research Laboratory(SCRL) Sindh Institute of Urology and Transplantation(SIUT)Karachi 74200SindhPakistan

BACKGROUND Zinc(Zn)is the second most abundant trace element after Fe,present in the human *** is frequently reported in association with cell growth and proliferation,and its deficiency is considered to be a major disease contributing *** To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord(hUC)-derived mesenchymal stem cells(MSCs).METHODS hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry,immunophenotyping,and tri-lineage *** impact of Zn on cytotoxicity and proliferation was determined by MTT and Alamar blue *** determine the effect of Zn on population doubling time(PDT),hUC-MSCs were cultured in media with and without Zn for several *** in vitro scratch assay was performed to analyze the effect of Zn on the wound healing and migration capability of hUC-MSCs.A cell adhesion assay was used to test the surface adhesiveness of *** analysis of genes involved in the cell cycle,proliferation,migration,and selfrenewal of hUC-MSCs was performed by quantitative real-time polymerase chain *** protein expression of Lin28,a pluripotency marker,was analyzed by *** Zn at lower concentrations enhanced the rate of proliferation but at higher concentrations(>100μM),showed concentration dependent cytotoxicity in ***-MSCs treated with Zn exhibited a significantly greater healing and migration rate compared to untreated *** also increased the cell adhesion rate,and colony forming efficiency(CFE).In addition,Zn upregulated the expression of genes involved in the cell cycle(CDC20,CDK1,CCNA2,CDCA2),proliferation(transforming growth factorβ1,GDF5,hypoxia-inducible factor 1α),migration(CXCR4,VCAM1,VEGF-A),and self-renewal(OCT4,SOX2,NANOG)of *** of Lin28 protein was significantly increased in cells treated with *** Our findings suggest that zinc enhances the proliferat

关键词： human umbilical cord Mesenchymal stem cells Zinc Cell proliferation In vitro expansion

Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine

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World Journal of Stem Cells 2024年第4期16卷 410-433页

作者： Shafiqa Naeem Rajput Bushra Kiran Naeem Anwar Ali Asmat Salim Irfan Khan Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Surgical Unit 4 Dr.Ruth KM Pfau Civil HospitalKarachi 74400Pakistan Department of Physiology University of KarachiKarachi 75270Pakistan Center for Regenerative Medicine and Stem Cells Research and Department of Ophthalmology and Visual SciencesThe Aga Khan UniversityKarachi 74800SindhPakistan

BACKGROUND Stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple *** humans,their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or *** suggested that mesenchymal stem cells(MSCs),necessary for repair and regeneration via transplantation,require doses ranging from 10 to 400 million ***,the limited expansion of MSCs restricts their therapeutic *** To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy *** human umbilical cord(hUC)tissue derived MSCs were obtained and *** cultured cells were subjected to the following evaluation pro-cedures:Immunophenotyping,immunocytochemical staining,trilineage differentiation,population doubling time and number,gene expression markers for proliferation,cell cycle progression,senescence-associatedβ-galactosidase assay,human telomerase reverse transcriptase(hTERT)expression,mycoplasma,cytomegalovirus and endotoxin *** Analysis of pluripotent gene markers Oct4,Sox2,and Nanog in recultured hUC-MSC revealed no significant *** immunophenotypic markers CD90,CD73,CD105,CD44,vimentin,CD29,Stro-1,and Lin28 were positively expressed by these recultured expanded MSCs,and were found negative for CD34,CD11b,CD19,CD45,and *** recultured hUC-MSC population continued to expand through passage *** gene expression of Pax6,BMP2,and TGFb1 showed no significant variation between recultured hUC-MSC ***,a significant increase(P<0.001)in the mitotic phase of the cell cycle was observed in recultured *** senescence markers(hTERT expression andβ-galactosidase activity)did not show any negative effect on recultured hUC-

关键词： human umbilical cord Mesenchymal stem cells Expansion Cell proliferation In vitro expansion Senescence

Immobilization of hUC-MSCs conditioned medium on 3D PLLA collagen-coated matrix enhances diabetic wound healing progression

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Engineered Regeneration 2024年第3期5卷 421-431页

作者： Siufui Hendrawan Olivia Marcelina Sukmawati Tansil Tan Hans Ulrich Baer Tarumanagara human Cell Technology Laboratory Faculty of MedicineTarumanagara UniversityJakarta 11440Indonesia Department of Biochemistry and Molecular Biology Faculty of MedicineTarumanagara UniversityJakarta 11440Indonesia Department of Dermato-venereology Faculty of MedicineTarumanagara UniversityJakarta 11440Indonesia Baermed Centre of Abdominal SurgeryHirslanden Clinic 8032 ZürichSwitzerland Department of Visceral and Transplantation Surgery University of BernSwitzerland

Conditioned medium(CM)derived from human umbilical cord-mesenchymal stem cells(hUC-MSCs)which con-tains numerous amounts of growth factors,has demonstrated potential in treatment of diabetic ***,for practical application,a biodegradable supporting material is needed to hold the CM and fill in the injury site,where deep cavity wounds are often present in diabetic ***-l-lactic acid matrix coated with collagen(PLLA/CC)is a suitable carrier due to its biodegradability and ***,we present a method to immobilize the hUC-MSCs CM on PLLA/CC through freeze-drying process(PLLA/CC CM FD).When seeded on PLLA/CC CM FD,fibroblasts had an increased cellular function in producing collagen;although no enhancement in cell viability was ***,implantation of PLLA/CC CM FD on the wound of diabetic rats showed improvement in wound closure and collagen deposition in the wound ***,this study exhibits the potential of PLLA/CC CM FD as a therapy for diabetic deep cavity wound.

关键词： PLLA matrix Diabetic wound Conditioned medium human umbilical cord Mesenchymal stem cell

Transcription regulators differentiate mesenchymal stem cells into chondroprogenitors,and their in vivo implantation regenerated the intervertebral disc degeneration

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World Journal of Stem Cells 2022年第2期14卷 163-182页

作者： Shumaila Khalid Sobia Ekram Asmat Salim G.Rasul Chaudhry Irfan Khan Dr.Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270SindhPakistan Department of Biological Sciences Oakland UniversityRochesterMI 48309United States

BACKGROUND Intervertebral disc degeneration(IVDD)is the leading cause of lower back *** degeneration is characterized by reduced cellularity and decreased production of extracellular matrix(ECM).Mesenchymal stem cells(MSCs)have been envisioned as a promising treatment for degenerative ***-based therapy using ECM-producing chondrogenic derivatives of MSCs has the potential to restore the functionality of the intervertebral disc(IVD).AIM To investigate the potential of chondrogenic transcription factors to promote differentiation of human umbilical cord MSCs into chondrocytes,and to assess their therapeutic potential in IVD *** MSCs were isolated and characterized morphologically and immunologically by the expression of specific *** were then transfected with Sox-9 and Six-1 transcription factors to direct differentiation and were assessed for chondrogenic lineage based on the expression of specific *** differentiated MSCs were implanted in the rat model of *** regenerative potential of transplanted cells was investigated using histochemical and molecular analyses of *** Isolated cells showed fibroblast-like morphology and expressed CD105,CD90,CD73,CD29,and Vimentin but not CD45 *** of Sox-9 and Six-1 greatly enhanced the gene expression of transforming growth factor beta-1 gene,BMP,Sox-9,Six-1,and Aggrecan,and protein expression of Sox-9 and *** implanted cells integrated,survived,and homed in the degenerated intervertebral *** grading showed that the transfected MSCs regenerated the IVD and restored normal *** Genetically modified MSCs accelerate cartilage regeneration,providing a unique opportunity and impetus for stem cell-based therapeutic approach for degenerative disc diseases.

关键词： Intervertebral disc degeneration human umbilical cord Transcription factors Mesenchymal stem cells Gene expression Regeneration