期刊文献+
共找到1,071篇文章
< 1 2 54 >
每页显示 20 50 100
Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons
1
作者 Yalan Chen Junxin Kuang +5 位作者 Yimei Niu Hongyao Zhu Xiaoxia Chen Kwok-Fai So Anding Xu Lingling Shi 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期908-914,共7页
Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vi... Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases. 展开更多
关键词 dopaminergic neurons FGF signal induced pluripotent stem cells MiDBRAiN neural differentiation SHH signal SMAD signal WNT signal
下载PDF
Patient-derived induced pluripotent stem cells with a MERTK mutation exhibit cell junction abnormalities and aberrant cellular differentiation potential
2
作者 Hang Zhang Ling-Zi Wu +1 位作者 Zhen-Yu Liu Zi-Bing Jin 《World Journal of Stem Cells》 SCIE 2024年第5期512-524,共13页
BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying ... BACKGROUND Human induced pluripotent stem cell(hiPSC)technology is a valuable tool for generating patient-specific stem cells,facilitating disease modeling,and invest-igating disease mechanisms.However,iPSCs carrying specific mutations may limit their clinical applications due to certain inherent characteristics.AIM To investigate the impact of MERTK mutations on hiPSCs and determine whether hiPSC-derived extracellular vesicles(EVs)influence anomalous cell junction and differentiation potential.METHODS We employed a non-integrating reprogramming technique to generate peripheral blood-derived hiPSCs with and hiPSCs without a MERTK mutation.Chromo-somal karyotype analysis,flow cytometry,and immunofluorescent staining were utilized for hiPSC identification.Transcriptomics and proteomics were employed to elucidate the expression patterns associated with cell junction abnormalities and cellular differentiation potential.Additionally,EVs were isolated from the supernatant,and their RNA and protein cargos were examined to investigate the involvement of hiPSC-derived EVs in stem cell junction and differentiation.RESULTS The generated hiPSCs,both with and without a MERTK mutation,exhibited normal karyotype and expressed pluripotency markers;however,hiPSCs with a MERTK mutation demonstrated anomalous adhesion capability and differentiation potential,as confirmed by transcriptomic and proteomic profiling.Furthermore,hiPSC-derived EVs were involved in various biological processes,including cell junction and differentiation.CONCLUSION HiPSCs with a MERTK mutation displayed altered junction characteristics and aberrant differentiation potential.Furthermore,hiPSC-derived EVs played a regulatory role in various biological processes,including cell junction and differentiation. 展开更多
关键词 Cell junction Cellular differentiation Extracellular vesicle Human induced pluripotent stem cells TRANSCRiPTOMiCS Proteomics
下载PDF
The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways 被引量:1
3
作者 Sen Zeng Honglan Yang +8 位作者 Binghao Wang Yongzhi Xie Ke Xu Lei Liu Wanqian Cao Xionghao Liu Beisha Tang Mujun Liu Ruxu Zhang 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期205-211,共7页
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus... Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction. 展开更多
关键词 antisense oligonucleotides cell cycle arrest Charcot-Marie-Tooth disease 2Z induced pluripotent stem cells MAPK/ERK Pi3K/Akt PROLiFERATiON spinal muscular atrophy-like
下载PDF
Advances in the differentiation of pluripotent stem cells into vascular cells
4
作者 Yi-Chang Jiao Ying-Xin Wang +4 位作者 Wen-Zhu Liu Jing-Wen Xu Yu-Ying Zhao Chuan-Zhu Yan Fu-Chen Liu 《World Journal of Stem Cells》 SCIE 2024年第2期137-150,共14页
Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood ve... Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed. 展开更多
关键词 induced pluripotent stem cell Blood vessels Vascular organoids Endothelial cells Smooth muscle cells PERiCYTES Tissue engineering vascular graft
下载PDF
Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes 被引量:4
5
作者 Hai-Li Lang Yan-Zhi Zhao +4 位作者 Ren-Jie Xiao Jing Sun Yong Chen Guo-Wen Hu Guo-Hai Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第3期609-617,共9页
Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,ho... Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction. 展开更多
关键词 diabetes mellitus hippocampus induced pluripotent stem cell mesenchymal stem cell miRNA neural stem cell NEUROGENESiS postoperative cognitive dysfunction signaling pathway small extracellular vesicle
下载PDF
The combined application of stem cells and three-dimensional bioprinting scaffolds for the repair of spinal cord injury 被引量:3
6
作者 Dingyue Ju Chuanming Dong 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第8期1751-1758,共8页
Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and t... Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury. 展开更多
关键词 BiOMATERiALS embryonic stem cells induced pluripotent stem cells mesenchymal stem cells nerve regeneration spinal cord injury stem cell therapy stem cells three-dimensional bioprinting
下载PDF
Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites
7
作者 Kirsty Goncalves Stefan Przyborski 《Neural Regeneration Research》 SCIE CAS 2025年第9期2645-2654,共10页
Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is be... Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner. 展开更多
关键词 Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron NOGO Rho A ROCK stem cell three-dimensional culture
下载PDF
Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases
8
作者 Hui-Si Yang Yue-Xiang Zheng +2 位作者 Xue Bai Xiu-Ying He Ting-Hua Wang 《World Journal of Orthopedics》 2024年第10期918-931,共14页
Urine-derived stem cells(USCs)are derived from urine and harbor the potential of proliferation and multidirectional differentiation.Moreover,USCs could be reprogrammed into pluripotent stem cells[namely urine-derived ... Urine-derived stem cells(USCs)are derived from urine and harbor the potential of proliferation and multidirectional differentiation.Moreover,USCs could be reprogrammed into pluripotent stem cells[namely urine-derived induced pluripotent stem cells(UiPSCs)]through transcription factors,such as octamer binding transcription factor 4,sex determining region Y-box 2,kruppel-like factor 4,myelocytomatosis oncogene,and Nanog homeobox and protein lin-28,in which the first four are known as Yamanaka factors.Mounting evidence supports that USCs and UiPSCs possess high potential of neurogenic,myogenic,and osteogenic differentiation,indicating that they may play a crucial role in the treatment of neurological and musculoskeletal diseases.Therefore,we summarized the origin and physiological characteristics of USCs and UiPSCs and their therapeutic application in neurological and musculoskeletal disorders in this review,which not only contributes to deepen our understanding of hallmarks of USCs and UiPSCs but also provides the theoretical basis for the treatment of neurological and musculoskeletal disorders with USCs and UiPSCs. 展开更多
关键词 Urine-derived stem cells Urine-derived induced pluripotent stem cells Neurological diseases Musculoskeletal diseases Treatment prospect
下载PDF
Neural lineage differentiation of human pluripotent stem cells:Advances in disease modeling 被引量:2
9
作者 Yuan-Wei Yan Eddie S Qian +1 位作者 Lauren E Woodard Julie Bejoy 《World Journal of Stem Cells》 SCIE 2023年第6期530-545,共16页
Brain diseases affect 1 in 6 people worldwide.These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer’s disease.Recent advancements in tissue-en... Brain diseases affect 1 in 6 people worldwide.These diseases range from acute neurological conditions such as stroke to chronic neurodegenerative disorders such as Alzheimer’s disease.Recent advancements in tissue-engineered brain disease models have overcome many of the different shortcomings associated with the various animal models,tissue culture models,and epidemiologic patient data that are commonly used to study brain disease.One innovative method by which to model human neurological disease is via the directed differentiation of human pluripotent stem cells(hPSCs)to neural lineages including neurons,astrocytes,and oligodendrocytes.Three-dimensional models such as brain organoids have also been derived from hPSCs,offering more physiological relevance due to their incorporation of various cell types.As such,brain organoids can better model the pathophysiology of neural diseases observed in patients.In this review,we will emphasize recent developments in hPSC-based tissue culture models of neurological disorders and how they are being used to create neural disease models. 展开更多
关键词 induced pluripotent stem cells ASTROCYTES OLiGODENDROCYTES MiCROGLiA Brain organoids Assembloids
下载PDF
Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing 被引量:1
10
作者 Li-Jun Wu Wei Lin +5 位作者 Jian-Jiang Liu Wei-Xin Chen Wen-Jun He Yuan Shi Xiao Liu Ke Li 《World Journal of Stem Cells》 SCIE 2023年第7期713-733,共21页
BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the eff... BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response. 展开更多
关键词 induced pluripotent stem cell KERATiNOCYTES Cell transplantation Burn wound healing COL7A1
下载PDF
Current overview of induced pluripotent stem cell-based blood-brain barrier-on-a-chip
11
作者 Arielly da Hora Alves Mariana Penteado Nucci +7 位作者 Nicole Mastandrea Ennes do Valle Juliana Morais Missina Javier Bustamante Mamani Gabriel Nery Albuquerque Rego Olivia Furiama Metropolo Dias Murilo Montenegro Garrigós Fernando Anselmo de Oliveira Lionel Fernel Gamarra 《World Journal of Stem Cells》 SCIE 2023年第6期632-651,共20页
BACKGROUND Induced pluripotent stem cells(iPSCs)show great ability to differentiate into any tissue,making them attractive candidates for pathophysiological investigations.The rise of organ-on-a-chip technology in the... BACKGROUND Induced pluripotent stem cells(iPSCs)show great ability to differentiate into any tissue,making them attractive candidates for pathophysiological investigations.The rise of organ-on-a-chip technology in the past century has introduced a novel way to make in vitro cell cultures that more closely resemble their in vivo environments,both structural and functionally.The literature still lacks consensus on the best conditions to mimic the blood-brain barrier(BBB)for drug screening and other personalized therapies.The development of models based on BBB-on-achip using iPSCs is promising and is a potential alternative to the use of animals in research.AIM To analyze the literature for BBB models on-a-chip involving iPSCs,describe the microdevices,the BBB in vitro construction,and applications.METHODS We searched for original articles indexed in PubMed and Scopus that used iPSCs to mimic the BBB and its microenvironment in microfluidic devices.Thirty articles were identified,wherein only 14 articles were finally selected according to the inclusion and exclusion criteria.Data compiled from the selected articles were organized into four topics:(1)Microfluidic devices design and fabrication;(2)characteristics of the iPSCs used in the BBB model and their differentiation conditions;(3)BBB-on-a-chip reconstruction process;and(4)applications of BBB microfluidic three-dimensional models using iPSCs.RESULTS This study showed that BBB models with iPSCs in microdevices are quite novel in scientific research.Important technological advances in this area regarding the use of commercial BBB-on-a-chip were identified in the most recent articles by different research groups.Conventional polydimethylsiloxane was the most used material to fabricate in-house chips(57%),whereas few studies(14.3%)adopted polymethylmethacrylate.Half the models were constructed using a porous membrane made of diverse materials to separate the channels.iPSC sources were divergent among the studies,but the main line used was IMR90-C4 from human fetal lung fibroblast(41.2%).The cells were differentiated through diverse and complex processes either to endothelial or neural cells,wherein only one study promoted differentiation inside the chip.The construction process of the BBB-on-a-chip involved previous coating mostly with fibronectin/collagen Ⅳ(39.3%),followed by cell seeding in single cultures(36%)or co-cultures(64%)under controlled conditions,aimed at developing an in vitro BBB that mimics the human BBB for future applications.CONCLUSION This review evidenced technological advances in the construction of BBB models using iPSCs.Nonetheless,a definitive BBB-on-a-chip has not yet been achieved,hindering the applicability of the models. 展开更多
关键词 induced pluripotent stem cells Cell differentiation Blood-brain barrier Neurovascular unit Organ-on-a-chip Microfluidic device
下载PDF
Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells 被引量:2
12
作者 何琼 王惠荟 +4 位作者 程涛 袁卫平 马钰波 蒋永平 任志华 《Chinese Medical Sciences Journal》 CAS CSCD 2017年第3期135-144,共10页
Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by ... Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay.Results The cell line bore a missense mutation in the 6th coding exon (c.676 C〉T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B. 展开更多
关键词 hemophilia B human induced pluripotent stem cells CRiSPR/Cas9 genetic correction hepatic differentiation
下载PDF
Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells 被引量:65
13
作者 Zhihua Song Jun Cai +13 位作者 Yanxia Liu Dongxin Zhao Jun Yong Shuguang Duo Xijun Song Yushan Guo Yang Zhao Han Qin Xiaolei Yin Chen Wu Jie Che Shichun Lu Mingxiao Ding Hongkui Deng 《Cell Research》 SCIE CAS CSCD 2009年第11期1233-1242,共10页
Human induced pluripotent stem (iPS) cells are similar to embryonic stem (ES) cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iP... Human induced pluripotent stem (iPS) cells are similar to embryonic stem (ES) cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iPS cells has not yet been reported. In this report, human iPS cells were induced to differentiate into hepatic cells by a stepwise protocol. The expression of liver cell markers and liver-related functions of the human iPS cell-derived cells were monitored and compared with that of differentiated human ES cells and primary human hepatocytes. Approximately 60% of the differentiated human iPS cells at day 7 expressed hepatic markers alpha fetoprotein and Alb. The differentiated cells at day 21 exhibited liver cell functions including albumin Asecretion, glycogen synthesis, urea production and inducible cytochrome P450 activity. The expression of hepatic markers and fiver-related functions of the iPS cellderived hepatic ceils were comparable to that of the human ES cell-derived hepatic cells. These results show that human iPS cells, which are similar to human ES cells, can be efficiently induced to differentiate into hepatocyte-like cells. 展开更多
关键词 induced pluripotent stem cells iPS DiFFERENTiATiON hepatic cells embryonic stem cells
下载PDF
Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study 被引量:13
14
作者 Yong Zhu Hong-Liang Hu +10 位作者 Peng Li Shi Yang Wei Zhang Hui Ding Ru-Hui Tian Ye Ning Ling-Ling Zhang Xi-Zhi Guo Zhan-Ping Shi Zheng Li Zuping He 《Asian Journal of Andrology》 SCIE CAS CSCD 2012年第4期574-579,共6页
Recent studies have reported that induced pluripotent stem (iPS) cells from mice and humans can differentiate into primordial germ cells. However, whether iPS cells are capable of producing male germ cells is not kn... Recent studies have reported that induced pluripotent stem (iPS) cells from mice and humans can differentiate into primordial germ cells. However, whether iPS cells are capable of producing male germ cells is not known. The objective of this study was to investigate the differentiation potential of mouse iPS cells into spermatogonial stem cells and late-stage male germ cells. We used an approach that combines in vitrodifferentiation and in vivotransplantation. Embryoid bodies (EBs) were obtained from iPS cells using leukaemia inhibitor factor (LIF)-free medium. Quantitative PCR revealed a decrease in Oct4 expression and an increase in StraSand Vasa mRNA in the EBs derived from iPS cells, iPS cell-derived EBs were induced by retinoic acid to differentiate into spermatogonial stem cells (SSCs), as evidenced by their expression of VASA, as well as CDH1 and GFRal, which are markers of SSCs. Furthermore, these germ cells derived from iPS cells were transplanted into recipient testes of mice that had been pre-treated with busulfan. Notably, iPS cell-derived SSCs were able to differentiate into male germ cells ranging from spermatogonia to round spermatids, as shown by VASA and SCP3 expression. This study demonstrates that iPS cells have the potential to differentiate into late-stage male germ cells. The derivation of male germ cells from iPS cells has potential applications in the treatment of male infertility and provides a model for uncovering the molecular mechanisms underlying male germ cell development. 展开更多
关键词 DiFFERENTiATiON induced pluripotent stem cells male germ cells retinoic acid TRANSPLANTATiON
下载PDF
Transfer of mitochondria from mesenchymal stem cells derived from induced pluripotent stem cells attenuates hypoxia-ischemia-induced mitochondrial dysfunction in PC12 cells 被引量:8
15
作者 Yan Yang Gen Ye +5 位作者 Yue-Lin Zhang Hai-Wei He Bao-Qi Yu Yi-Mei Hong Wei You Xin Li 《Neural Regeneration Research》 SCIE CAS CSCD 2020年第3期464-472,共9页
Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully... Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully understood.To address this issue,we first co-cultured 1.5×10^5 PC12 cells with mesenchymal stem cells that were derived from induced pluripotent stem cells at a ratio of 1:1,and then intervened with cobalt chloride(CoCl2)for 24 hours.Reactive oxygen species in PC12 cells was measured by Mito-sox.Mitochondrial membrane potential(ΔΨm)in PC12 cells was determined by JC-1 staining.Apoptosis of PC12 cells was detected by terminal deoxynucleotidal transferase-mediated dUTP nick end-labeling staining.Mitochondrial morphology in PC12 cells was examined by transmission electron microscopy.Transfer of mitochondria from the mesenchymal stem cells derived from induced pluripotent stem cells to damaged PC12 cells was measured by flow cytometry.Mesenchymal stem cells were induced from pluripotent stem cells by lentivirus infection containing green fluorescent protein in mitochondria.Then they were co-cultured with PC12 cells in Transwell chambers and treated with CoCl2 for 24 hours to detect adenosine triphosphate level in PC12 cells.CoCl2-induced PC12 cell damage was dose-dependent.Co-culture with mesenchymal stem cells significantly reduced apoptosis and restoredΔΨm in the injured PC12 cells under CoCl2 challenge.Co-culture with mesenchymal stem cells ameliorated mitochondrial swelling,the disappearance of cristae,and chromatin margination in the injured PC12 cells.After direct co-culture,mitochondrial transfer from the mesenchymal stem cells stem cells to PC12 cells was detected via formed tunneling nanotubes between these two types of cells.The transfer efficiency was greatly enhanced in the presence of CoCl2.More importantly,inhibition of tunneling nanotubes partially abrogated the beneficial effects of mesenchymal stem cells on CoCl2-induced PC12 cell injury.Mesenchymal stem cells reduced CoCl2-induced PC12 cell injury and these effects were in part due to efficacious mitochondrial transfer. 展开更多
关键词 apoptosis brain injury HYPOXiA-iSCHEMiA induced pluripotent stem cells mesenchymal stem cells MiTOCHONDRiAL membrane potential MiTOCHONDRiAL TRANSFER PC12 cells tunneling nanotubes
下载PDF
Methods of induced pluripotent stem cells for clinical application 被引量:9
16
作者 Tomohisa Seki Keiichi Fukuda 《World Journal of Stem Cells》 SCIE CAS 2015年第1期116-125,共10页
Reprograming somatic cells using exogenetic gene expression represents a groundbreaking step in regenerative medicine. Induced pluripotent stem cells(i PSCs) are expected to yield novel therapies with the potential to... Reprograming somatic cells using exogenetic gene expression represents a groundbreaking step in regenerative medicine. Induced pluripotent stem cells(i PSCs) are expected to yield novel therapies with the potential to solve many issues involving incurable diseases. In particular, applying i PSCs clinically holds the promise of addressing the problems of immune rejection and ethics that have hampered the clinical applications of embryonic stem cells. However, as i PSC research has progressed, new problems have emerged that need to be solved before the routine clinical application of i PSCs can become established. In this review, we discuss the current technologies and future problems of human i PSC generation methods for clinical use. 展开更多
关键词 induced pluripotent stem cells CELL REPROGRAMMiNG
下载PDF
Modelling mitochondrial dysfunction in Alzheimer’s disease using human induced pluripotent stem cells 被引量:6
17
作者 Kate Elizabeth Hawkins Michael Duchen 《World Journal of Stem Cells》 SCIE CAS 2019年第5期236-253,共18页
Alzheimer’s disease (AD) is the most common form of dementia. To date, only five pharmacological agents have been approved by the Food and Drug Administration for clinical use in AD, all of which target the symptoms ... Alzheimer’s disease (AD) is the most common form of dementia. To date, only five pharmacological agents have been approved by the Food and Drug Administration for clinical use in AD, all of which target the symptoms of the disease rather than the cause. Increasing our understanding of the underlying pathophysiology of AD will facilitate the development of new therapeutic strategies. Over the years, the major hypotheses of AD etiology have focused on deposition of amyloid beta and mitochondrial dysfunction. In this review we highlight the potential of experimental model systems based on human induced pluripotent stem cells (iPSCs) to provide novel insights into the cellular pathophysiology underlying neurodegeneration in AD. Whilst Down syndrome and familial AD iPSC models faithfully reproduce features of AD such as accumulation of Aβ and tau, oxidative stress and mitochondrial dysfunction, sporadic AD is much more difficult to model in this way due to its complex etiology. Nevertheless, iPSC-based modelling of AD has provided invaluable insights into the underlying pathophysiology of the disease, and has a huge potential for use as a platform for drug discovery. 展开更多
关键词 induced pluripotent stem cells Alzheimer's DiSEASE MiTOCHONDRiA
下载PDF
Using induced pluripotent stem cells as a tool for modelling carcinogenesis 被引量:5
18
作者 Emma L Curry Mohammad Moad +1 位作者 Craig N Robson Rakesh Heer 《World Journal of Stem Cells》 SCIE CAS 2015年第2期461-469,共9页
Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis... Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis are limited by lack of appropriate models for the development and pathogenesis of the disease based on human tissues. Primary culture of patient samples can help but is difficult to grow for a number of tissues. A potential opportunity to overcome these barriers is based on the landmark study by Yamanaka which demonstrated the ability of four factors;Oct4, Sox2, Klf4, and c-Myc to reprogram human somatic cells in to pluripotency. These cells were termed induced pluripotent stem cells(i PSCs) and display characteristic properties of embryonic stem cells. This technique has a wide range of potential uses including disease modelling, drug testing and transplantation studies. Interestingly i PSCs also share a number of characteristics with cancer cells including self-renewal and proliferation, expression of stem cell markers and altered metabolism. Recently, i PSCs have been generated from a number of human cancer cell lines and primary tumour samples from a range of cancers in an attempt to recapitulate the development of cancer and interrogate the underlying mechanisms involved. This review will outline the similarities between the reprogramming process and carcinogenesis, and how these similarities have been exploited to generate i PSC models for a number of cancers. 展开更多
关键词 induced pluripotent stem cells CANCER Model REPROGRAMMiNG
下载PDF
Thinking outside the liver: Induced pluripotent stem cells for hepatic applications 被引量:4
19
作者 Mekala Subba Rao Mitnala Sasikala D Nageshwar Reddy 《World Journal of Gastroenterology》 SCIE CAS 2013年第22期3385-3396,共12页
The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos.... The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications. 展开更多
关键词 LiVER stem cells HEPATOCYTES Disease modeling Drug toxicity Clinical APPLiCATiONS PATiENT-SPECiFiC induced pluripotent stem cell-derived HEPATOCYTES
下载PDF
Differentiation of retinal ganglion cells from induced pluripotent stem cells: a review 被引量:4
20
作者 Shang-Li Ji Shi-Bo Tang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2019年第1期152-160,共9页
Glaucoma is a common optic neuropathy that is characterized by the progressive degeneration of axons and the loss of retinal ganglion cells(RGCs). Glaucoma is one of the leading causes of irreversible blindness worldw... Glaucoma is a common optic neuropathy that is characterized by the progressive degeneration of axons and the loss of retinal ganglion cells(RGCs). Glaucoma is one of the leading causes of irreversible blindness worldwide. Current glaucoma treatments only slow the progression of RGCs loss. Induced pluripotent stem cells(iPSCs) are capable of differentiating into all three germ layer cell lineages. iPSCs can be patient-specific,making iPSC-derived RGCs a promising candidate for cell replacement. In this review, we focus on discussing the detailed approaches used to differentiate iPSCs into RGCs. 展开更多
关键词 GLAUCOMA RETiNAL GANGLiON cells induced pluripotent stem cells DiFFERENTiATiON
下载PDF
上一页 1 2 54 下一页 到第
使用帮助 返回顶部