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The applications of induced pluripotent stem(iPS)cells in drug development

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Frontiers in Biology 2011年第1期6卷 52-57页

作者： Shulong YANG Xuelian WANG Jinmiao LIU Zhao LIU Jiaxue HUANG Life Technologies Vcanland Holding Group Union stem cell&Gene Engineering Co.LTD Tianjin 300384China School of Pharmaceutical Science and Technology Tianjin UniversityTianjin 300072China

The introduction of induced pluripotent stem(iPS)cells has been a milestone in the field of regenerative medicine and drug *** cells can provide a continuous and individualized source of stem cells and are considered to hold great potential for economically feasible personalized stem cell *** diseases might potentially be cured by iPS cell-based therapy including Parkinson’s disease,Alzheimer’s disease,Huntington disease,ischemic heart disease,diabetes and so ***,iPS cells derived from patients suffering from unique incurable diseases can be developed into patient-and disease-specific cell *** cells can be used as an effective approach to study the mechanisms of diseases,providing useful tools for drug discovery,development and *** development of suitable methods for the culture and expansion of iPS cells and their differentiated progenies make feasible modern drug discovery techniques such as high-throughput ***,iPS cells can be applied in the field of toxicological and pharmacokinetics *** review focuses on the applications of iPS cells in the field of pharmaceutical industry.

关键词： induced pluripotent stem(iPS)cells drug discovery

Expression and Identification of a Novel Apoptosis Gene Spata17(MSRG-11)in Mouse Spermatogenic cells

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Acta Biochimica et Biophysica Sinica 2006年第1期38卷 37-45页

作者： Yun DENG Liang-Sha HU Guang-Xiu LU National Center for Human stem cell Research and Engineering,Institute of Human Reproductive and stem cell Engineering,Central South University.Changsha 410078,China National Center for Human stem cell Research and Engineering Institute of Human Reproductive and Stem Cell Engineering Central South University Changsha 410078 China

In this study,anti-spermatogenesis-associated 17 (Spatal7) polyclonal antibody was preparedby immunizing New Zealand white rabbits with a synthesized peptide corresponding to the amino acid se-quence 7-23 of the mouse Spata17 *** analysis revealed that Spata17 proteinwas most abundant in the cytoplasm of round spermatids and elongating spermatids within seminiferoustubules of the adult *** expression of Spata17 mRNA in cultured mouse spermatogonia (GC-1) cellswas almost *** an experimental unilateral cryptorchidism model of an adult mouse,the expres-sion of Spata17 mRNA had no obvious difference with the normal testis until postoperation day 1,butgradually decreased from day 3 and was almost undetectable on day *** analysisrevealed that the protein was almost undetectable within seminiferous tubules of an experimental unilateralcryptorchidism model of the adult testis on postoperation day *** cytometry analysis showed that theexpression of Spatal7 protein in the GC-1 cell line could accelerate GC-1 cell *** effect increaseswith the increasing of the transfected dose of pcDNA3.1 (-)/*** Hoechst 33258 staining,a classicalway of identifying apoptotic cells,we further confirmed that the apoptosis was induced by expression ofSpata17 in transfected GC-1 cells.

关键词： spermatogenesis-associated 17(Spata17)gene MSRG-11 testis spermatogenic cell apoptosis

Deriving striatal projection neurons from human pluripotent stem cells with Activin A

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Neural Regeneration Research 2015年第12期10卷 1914-1916页

作者： Zoe Noakes Marija Fjodorova Meng Li stem cell Neurogenesis group Neuroscience and Mental Health Research InstituteSchool of Medicine and School of BioscienceCardiff University

The striatum is the main input structure of the basal ganglia and is involved in voluntary motor control,habit learning and reward *** spiny neurons（MSNs）comprise80%and 95%of striatal neurons in primates and rodents... 详细信息

关键词： cell MSNs PSCs Deriving striatal projection neurons from human pluripotent stem cells with Activin A stem

Haploid embryonic stem cells:an ideal tool for mammalian genetic analyses

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Protein & cell 2012年第11期3卷 806-810页

作者： Linyu Shi Hui Yang Jinsong Li group of Epigenetic Reprogramming State Key Laboratory of Cell BiologyInstitute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of ***,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic ***,mouse haploid embryonic stem(haES)cells have been successfully isolated from parthenogenetic and androgenetic embryos,providing an ideal tool for genetic *** these studies,mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous *** particular,haES cells from androgenetic embryos can be employed as novel,renewable form of fertilization agent for yielding live-born mice via injection into oocytes,thus showing the possibility that genetic analysis can be extended from cellular level to organism level.

关键词： haploid embryonic stem cells parthenogenetic embryos androgenetic embryos genetic screening diploid genomic imprinting

Comparison of Different Culture Mode for Long-term Expansion of Neural stem cells

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生物医学工程学杂志 2005年第S1期22卷 113-115页

作者： Ke ZHENG Dan GE Tian-Qing LIU~Δ Xue-Hu MA(stem cell and Tissue Engineering Laboratory, Dalian University of Technology, Dalian 116024, China) stem cell and Tissue Engineering Laboratory Dalian University of Technology Dalian 116024 China

1 IntroductionThe mammalian central nervous system(CNS) is incredibly complex and possesses only a limited ability to recover from damage[1]. Fortunately, the discovery of self-renewing stem cell populations within th... 详细信息

关键词： NSCs cell Comparison of Different Culture Mode for Long-term Expansion of Neural stem cells Long

Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury:A multicenter,double-blind,placebo-controlled,randomized trial

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Journal of Integrative Medicine 2024年第3期22卷 279-285页

作者： Jia-jia Wu Tian-yi Zhang Ying-hui Qi Min-yan Zhu Yan Fang Chao-jun Qi Li-ou Cao Ji-fang Lu Bo-han Lu Lu-min Tang Jian-xiao Shen Shan Mou Department of Nephrology Molecular Cell Lab for Kidney DiseaseShanghai Peritoneal Dialysis Research CenterUremia Diagnosis and Treatment CenterRenji Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200127China Department of Nephrology Shanghai Pudong New Area Punan HospitalShanghai 200125China Department of Nephrology Ningbo Hangzhou Bay HospitalNingbo 315336Zhejiang ProvinceChina

Background:Yiqi Peiyuan(YQPY)prescription,a composite prescription of traditional Chinese medicine,has been used to prevent or delay the continued deterioration of renal function after acute kidney injury(AKI)in some institutions and has shown considerable ***:This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with ***,setting,participants and interventions:This is a prospective,double-blind,multicenter,randomized,and placebo-controlled clinical trial.A total of 144 enrolled participants were randomly allocated to two groups according to a randomization ***,caregivers and investigators assessing the outcomes were blinded to group *** in the YQPY group received 36 g YQPY granules twice a day for 28 *** in the placebo group received a placebo in the same dose as the YQPY *** outcome measures:The primary outcome was the change in the estimated glomerular filtration rate(eGFR)between baseline and after 4 and 24 weeks of *** secondary outcomes were the change of serum creatinine(Scr)level between baseline and after treatment,and the incidence of endpoint events,defined as eGFR increasing by more than 25%above baseline,eGFR>75 mL/min per1.73 m2or the composite endpoint,which was defined as the sum of patients meeting either of the above ***:Data from a total of 114 patients(59 in the YQPY group and 55 in the control group)were *** mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two *** further subgroup analysis(22 in the YQPY group and 31 in the control group),the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2in the YQPY group and 5.78 mL/min per1.73 m2in the placebo group,and the mean difference between groups was 21.61 mL/min per 1.73 m2(Pgroup and 5(16.1%)in the placebo g

关键词： Chinese herbal medicine Randomized controlled trial Acute kidney injury Renal function

Biofabrication of size-controlled liver microtissues incorporated with ECM-derived microparticles to prolong hepatocyte function

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Bio-Design and Manufacturing 2021年第4期4卷 790-805页

作者： Zahra Heydari Ibrahim Zarkesh Mohammad-Hossein Ghanian Mahdokht HAghdaei Svetlana Kotova Ensieh Zahmatkesh Zahra Farzaneh Abbas Piryaei Iman Akbarzadeh Anastasia Shpichka Roberto Gramignoli Peter Timashev Hossein Baharvand Massoud Vosough Department of Developmental Biology University of Science and CultureACECR14155-4364 TehranIran Department of Regenerative Medicine Cell Science Research CentreRoyan Institute for Stem Cell Biology and TechnologyACECR14155-4364 TehranIran Department of stem cells and Developmental Biology Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR14155-4364 TehranIran Department of cell Engineering Cell Science Research CenterRoyan Institute for Stem Cell Biology and TechnologyACECR14155-4364 TehranIran Transplant Research Center Shiraz University of Medical Sciences71936-13311 ShirazIran N.N.Semenov Federal Research Center for Chemical Physics Russian Academy of SciencesMoscow 117977Russia Department of Biology and Anatomical Sciences School of MedicineShahid Beheshti University of Medical Sciences14155-4364 TehranIran Department of Tissue Engineering and Applied cell Sciences School of Advanced Technologies in MedicineShahid Beheshti University of Medical Sciences14155-4364 TehranIran Institute for Regenerative Medicine Sechenov UniversityMoscow 117977Russia Division of Pathology Department of Laboratory MedicineKarolinska Institute17177 StockholmSweden

Multicellular microtissues of primary human hepatocytes(PHHs)co-cultured with other supporting cell types are a promis-ing model for drug screening and toxicological ***,these liver microtissues(LMs)rapidly lose their functions during ex vivo ***,in order to mimic the cellular and structural hepatic microenvironment,we co-cultured PHHs with human mesenchymal stromal cells(MSCs)and human umbilical vein endothelial cells(HUVECs)in the presence of cell-sized microparticles(MPs)derived from liver extracellular matrix(LEMPs).The microwell culture platform enabled biofabrication of size-controlled multicellular microtissues(PHH:HUVEC:MSC=3:2:1)with efficient LEMP incorporation(about 70%at a 2:1 ratio of cells:MP).The biofabricated liver microtissues(BLMs)were cultured ex vivo for 14 days and compared to the cell-only LM in terms of gene and protein expression,functional activity,cytochrome P450(CYP450)enzyme inducibility,and drug *** results supported superior hepatic-related gene expression,functional activity,and polarity for PHH in BLM compared to ***450 enzyme inducibility and dose-responsive sensitivity to toxic drugs were significantly higher in the BLM *** conclusion,microtissue engineering by incorporation of tissue-specific microparticles within a multicellular microtissue can offer some advantages for drug discovery studies and cell transplantation *** the near future,this approach could generate a scalable platform of several functional biofabricated microtissues representing different organs.

关键词： Liver microtissue Hepatocyte maintenance Microparticles Decellularized tissue Drug screening

Familial Alzheimer's disease modelling using induced pluripotent stem cell technology

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World Journal of stem cells 2014年第2期6卷 239-247页

作者： Lisa Mohamet Natalie J Miazga Christopher M Ward stem cell Biology group Core Technology FacilityFaculty of Human and Medical SciencesThe University of Manchester

Alzheimer’s disease(AD)is a progressive neurodegenerative disease in which patients exhibit gradual loss of memory that impairs their ability to learn or carry out daily *** of AD is difficult,particularly in early stages of the disease,and largely consists of cognitive assessments,with only one in four patients being correctly *** of novel therapeutics for the treatment of AD has proved to be a lengthy,costly and relatively unproductive process with attrition rates of>90%.As a result,there are no cures for AD and few treatment options available for ***,there is a pressing need for drug discovery platforms that can accurately and reproducibly mimic the AD phenotype and be amenable to high content screening ***,we discuss the use of induced pluripotent stem cells(iPSCs),which can be derived from adult cells,as a method of recapitulation of AD phenotype in *** assess their potential use in high content screening assays and the barriers that exist to realising their full potential in predictive efficacy,toxicology and disease *** present,a number of limitations need to be addressed before the use of iPSC technology can be fully realised in AD therapeutic ***,whilst the use of AD-derived iPSCs in drug discovery remains a fledgling field,it is one with immense potential that is likely to reach fruition within the next few years.

关键词： Human induced pluripotent stem cells Alzheimer’ s disease Neurodegenerative diseases High-throughput screening assays Cholinergic neurons Drug discovery Stratified medicine

Absence of interleukin-1 receptor 1 increases excitatory and inhibitory scaffolding protein expression and microglial activation in the adult mouse hippocampus

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cellular & Molecular Immunology 2015年第5期12卷 645-647页

作者： Una Avdic Deepti Chugh Harer Osman Katie Chapman Johanna Jackson Christine T Ekdahl Inflammation and stem cell Therapy group Division of Clinical Neurophysiology Lund University Lund Sweden Lund Epilepsy Center Lund University Lund Sweden Current address: Division of Neurology Department of Clinical Sciences Lund University Lund Sweden Current address: Lilly UK Windlesham Surrey UK

In the present study, we demonstrate that adult mice lacking interleukin- 1 receptor 1 （IL- 1R1） exhibit increased express- ion of both the excitatory scaffolding protein postsynaptic density-95 （PSD-95） and inhibitory scaffolding proteinge- phyrin, respectively, in the hippocampus. The morphology of hippocampal microglia is also altered towards a more activated phenotype. These results indicate an important role for IL-1 signaling in maintaining physiological conditions in both neurons and microglia.

关键词： increases excitatory inhibitory scaffolding