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Acta Pharmaceutica Sinica B 2022年第8期12卷 3215-3232页

作者： Yaosheng Li Honghui Wu Xinchi Jiang Yunfei Dong Juanjuan Zheng Jianqing Gao Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Dr.Li Dak Sum&Yip Yio Chin Center for stem Cell and Regenerative Medicine Zhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China

The clinical translation of stem cells and their extracellular vesicles(EVs)-based therapy for central nervous system(CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal(IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain-blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

关键词： stem cells Extracellular vesicles Central nervous system disorders Intranasal clinical translation Stroke Neurodegenerative disease Glioma

From stem cells to red blood cells:how far away from the clinical application?

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Science China(Life Sciences) 2014年第6期57卷 581-585页

作者： XIE XiaoYan LI YanHua PEI XueTao stem Cell and Regenerative Medicine Lab Beijing Institute of Transfusion Medicine South China Research Center for stem Cell and Regenerative Medicine

The generation of red blood cells(RBCs)from stem cells provides a solution for deficiencies in blood ***,primary hematopoietic stem cells,embryonic stem cells and induced pluripotent stem cells have shown the potential to produce fully mature ***,we discuss the advantages,induction protocols,progress and possible clinical applications of stem cells in RBC production.

关键词： stem cells red blood cells differentiation clinical application

clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells

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Neural Regeneration Research 2016年第5期11卷 702-705页

作者： Peter Deng Audrey Torrest Kari Pollock Heather Dahlenburg Geralyn Annett Jan A.Nolta Kyle D.Fink stem Cell Program and Institute for Regenerative Cures University of California Davis Health System

Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells（MSC） to secrete brain-derived neurotrophic factor（BDNF） supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington＇s disease（HD）. There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis（ALS）, spinocerebellar ataxia（SCA）, Alzheimer＇s disease, and some forms of Parkinson＇s disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system.

关键词： mesenchymal stem cells neurodegenerative disorders, Huntington's disease genetic engineering brain derived neurotrophic factor

Functions of nuclear factor Y in nervous system development,function and health

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Neural Regeneration Research 2025年第10期20卷 2887-2894页

作者： Pedro Moreira Roger Pocock Development and stem cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes,one of the most common motifs found in gene promoters and *** the last 30 years,research has revealed that the nuclear factor Y complex controls many aspects of brain development,including differentiation,axon guidance,homeostasis,disease,and most recently ***,a complete understanding of transcriptional regulatory networks,including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains *** this review,we explore the nuclear factor Y complex’s role and mode of action during brain development,as well as how genomic technologies may expand understanding of this key regulator of gene expression.

关键词： axon guidance CCAAT boxes neuronal degeneration neuronal differentiation neuronal regeneration nuclear factor Y complex transcription factor transcriptional regulation

Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications

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World Journal of stem cells 2022年第1期14卷 54-75页

作者： Carla Vicinanza Elisabetta Lombardi Francesco Da Ros Miriam Marangon Cristina Durante Mario Mazzucato Francesco Agostini stem Cell Unit Centro di Riferimento Oncologico di AvianoIRCCSAviano 33081Italy

Mesenchymal stem stromal cells(MSC)are characterized by the intriguing capacity to home toward cancer cells after systemic ***,MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against *** cancer patients,MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was ***,the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor ***,induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic *** vivo cell modifications are,thus,required to improve anti-cancer properties of *** based cellular therapy products must be handled in compliance with good manufacturing practice(GMP)*** the present review we include MSCimproving manipulation approaches that,even though actually tested at preclinical level,could be compatible with GMP *** particular,we describe possible approaches to improve MSC homing on cancer,including genetic engineering,membrane modification and cytokine ***,we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic *** conclusion,we suggest that,to configure MSC as a powerful weapon against cancer,combinations of clinical grade compatible modification protocols that are currently selected,should be introduced in the final *** standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.

关键词： Cancer Mesenchymal stem stromal cells Good manufacturing practice Homing Targeted therapy Ex vivo cell modification

The effect of clinical-grade retinal pigment epithelium derived from human embryonic stem cells using different transplantation strategies

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Protein & Cell 2019年第6期10卷 455-460页

作者： Lei Wang Wei Wu Qi Gu Zengping Liu Qiyou Li Zhongwen Li Jinhui Fang Wenjing Liu Jun Wu Ying Zhang Liu Wang Haiwei Xu Wei Li Baoyang Hu Qi Zhou Zhengqin Yin Jie Hao Savaid Medical School University of Chinese Academy of Sciences Beijing 100049 China State Key Laboratory of stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Southwest Hospital/Southwest Eye Hospital Third Military Medical University (Army Medical University) Chongqing 400038 China Beijing stem Cell Bank Chinese Academy of Sciences Beijing 100190 Chin State Key Laboratory of Membrane Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China stem Cell and Regenerative Medicine Innovation Institute Chinese Academy of Sciences Beijing 100101 China

Dear Editor, Many forms of sight-threatening diseases, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD), are caused by the dysfunction, degeneration and loss of the retinal pigment epithelium (RPE)(Strauss, 2005). RPE cell transplantation may potentially recover or halt disease progression, in which human embryonic stem cells (hESCs) could serve as an unlimited donor source for RPE differentiation, and a few clinical trials have shown the safety and effective of transplantation of hESCs-derived RPE (hESC-RPE) for AMD patients (Schwartz et al., 2012;Schwartz etal., 2015;Song etal., 2015;da Cruz et al., 2018;Kashani et al., 2018;Liu et al., 2018).

关键词： Dear Editor Many forms RPE cell transplantation

Human neural stem cell-derived extracellular vesicles protect against ischemic stroke by activating the PI3K/AKT/mTOR pathway

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Neural Regeneration Research 2025年第11期20卷 3245-3258页

作者： Jiayi Wang Mengke Zhao Dong Fu Meina Wang Chao Han Zhongyue Lv Liang Wang Jing Liu stem Cell clinical Research Center The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina Dalian Innovation Institute of stem Cell and Precision Medicine DalianLiaoning ProvinceChina Institute(College)of Integrative Medicine Dalian Medical UniversityDalianLiaoning ProvinceChina

Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived *** lays a foundation for the development of potentially potent new treatment modalities for ischemic ***,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical *** promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic *** found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal *** human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase *** findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling ***,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety ***,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.

关键词： behavior exosome extracellular vesicles ischemic stroke mammalian target of rapamycin(mTOR) middle cerebral artery occlusion neural stem cells neuronal apoptosis phosphoinositide 3-kinase(PI3K) protein kinase B(AKT)

clinical efficacy and safety of mesenchymal stem cells in patients with diabetes mellitus

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Clinical efficacy and safety of mesenchymal stem cells in pa...

clinical implications of microRNAs in liver cancer stem cells

中国解剖学会2021年年会

作者： He Jingjing Kong Desheng Asiamah Ernest Amponsah Guo Ruiyun Feng Baofeng Ma Jun Timothy O’Brien Cui Huixian Department of Anatomy HMU-NUIG Joint Stem Cell Research CenterHebei Research Center for Stem Cell Medical Translation EngineeringHebei Medical University

Diabetes mellitus (DM) as a chronic metabolic disease is threatening human health *** aim of this study was to systematically review the evidence from RCTs and conduct comprehensive assessment of therapeutic efficacy and safety of mesenchymal stem cells (MSCs) in ***,Web of Science,Ovid,the Cochrane Library and CNKI were searched until April 30,2020.

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Chinese Journal of Cancer 2013年第8期32卷 419-426页

作者： Stella Chai Stephanie Ma Department of clinical Oncology Li Ka Shing Faculty of Medicine The University of Hong Kong State Key Laboratory for Liver Research Li Ka Shing Faculty of Medicine The University of Hong Kong

The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal, mainly due to late presentation, high recurrence rate, and frequent resistance to chemotherapy and radiotherapy. Accumulating evidence on the differential microRNA (miRNA) expression patterns between non-tumor and HCC tissues or between liver cancer stem cells (CSCs) and non-CSC subsets and the significant clinical implications of these differences suggest that miRNAs are a promising, non-invasive marker for the prognosis and diagnosis of the disease. This perspective article summarizes the current knowledge of miRNAs in liver CSCs and highlights the need for further investigations of the role of miRNAs in regulating liver CSC subsets for possible future clinical applications.

关键词：肝干细胞 microRNA 临床意义肝癌 miRNAs 肝细胞癌表达模式小RNA

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

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World Journal of stem cells 2023年第4期15卷 150-164页

作者： Tian-Yu Liang Li-Hai Lu Si-Yu Tang Zi-Hao Zheng Kai Shi Jing-Quan Liu Emergency and Critical Care Center Intensive Care UnitZhejiang Provincial People's Hospital(Affiliated People's HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina Fourth School of clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina The Second School of clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina Department of Respiratory Medicine The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310015Zhejiang ProvinceChina

Acute respiratory distress syndrome(ARDS)is a common and clinically devastating disease that causes respiratory *** and mortality of patients in intensive care units are stubbornly high,and various complications severely affect the quality of life of *** pathophysiology of ARDS includes increased alveolar–capillary membrane permeability,an influx of protein-rich pulmonary edema fluid,and surfactant dysfunction leading to severe *** present,the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema,which primarily improves symptoms,but the prognosis of patients with ARDS is still very *** stem cells(MSCs)are stromal cells that possess the capacity to self-renew and also exhibit multilineage *** can be isolated from a variety of tissues,such as the umbilical cord,endometrial polyps,menstrual blood,bone marrow,and adipose *** have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of ***,the potential of stem cells in treating ARDS has been explored via basic research and clinical *** efficacy of MSCs has been shown in a variety of in vivo models of ARDS,reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung *** article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.

关键词： Acute respiratory distress syndrome Mesenchymal stem cells Pulmonary edema Inflammatory response Tissue repair Pulmonary fibrosis