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Mesenchymal stem cell-derived exosomes: Versatile nanomaterials for skin wound treatment

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Nano Research 2024年第4期17卷 2836-2856页

作者： Yuzhen Xiao Hexi Li Junhui Zhang Songyun Yang Chunsen Zhang Yizhou Huang Xin Tang Huiqi Xie Department of Orthopedic Surgery and Orthopedic Research Institute Laboratory of Stem Cell and Tissue EngineeringState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China School of Basic Medical Sciences and Forensic Medicine Sichuan UniversityChengdu 610041China West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610041China Sports Medicine Center West China HospitalSichuan UniversityChengdu 610041China

Accumulating studies reveal that mesenchymal stem cells(MSCs)promote skin wound healing mainly through the paracrine ***,one of the crucial paracrine mediators in wound healing,are cell-derived nanosized membranous vesicles containing diverse bioactive *** the potent ability of modulating skin cell behaviors,MSC-derived exosomes(MSC-Exos)are regarded as a promising nanomaterial for regenerative wound *** hostile conditions,MSC-Exos are efficient in protecting skin cells from severe damage and restoring their *** to recent studies,MSC-Exos possess remarkable pro-healing effects in a variety of skin wounds,typically resulting in increased wound closure,inhibited scar tissue formation,and better restoration of skin *** further enhance the therapeutic potential of MSC-Exos,the development of applicable pretreatment strategies and the optimization of exosome delivery are under intensive ***,we summarize current research progress of MSC-Exos for skin wound treatment,with an emphasis on the biological effects of these nanovesicles,the repair mechanisms,and future challenges in clinical translation.

关键词： exosomes mesenchymal stem cells diabetic wounds burn wounds scar wound healing

Neuroprotective effects of neural stem cells pretreated with neuregulin1β on PC12 cells exposed to oxygen-glucose deprivation/reoxygenation

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Neural Regeneration Research 2023年第3期18卷 618-625页

作者： Qiu-Yue Zhai Yuan-Hua Ye Yu-Qian Ren Zhen-Hua Song Ke-Li Ge Bao-He Cheng Yun-Liang Guo Institute of Cerebrovascular Diseases Medical Research CenterThe Affiliated Hospital of Qingdao UniversityTaishan Scholars Construction Project Excellent Innovative Team of Shandong ProvinceQingdaoShandong ProvinceChina Department of Obstetrics The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Research Center of stem cells Shandong Haoyun International Hospital of Stem CellsJinanShandong ProvinceChina

Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion ***,NSCs are difficult to obtain owing to ethical *** addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical *** previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in *** this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of ***-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to *** has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R *** data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 *** findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.

关键词： ferroptosis p53 SLC7A11 GPX4 human umbilical cord-mesenchymal stem cells neural stem cells neuregulin1β neuroprotection oxygen-glucose deprivation/reoxygenation PC12 cell

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Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues

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Protein & Cell 2024年第8期15卷 594-611页

作者： Jian Wu Chaoye Wang Shuhui Sun Tianmin Ren Lijie Pan Hongyi Liu Simeng Hou Shen Wu Xuejing Yan Jingxue Zhang Xiaofang Zhao Weihai Liu Sirui Zhu Shuwen Wei Chi Zhang Xu Jia Qi Zhang Ziyu Yu Yehong Zhuo Qi Zhao Chenlong Yang Ningli Wang Beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Key Laboratory of Ophthalmology and Visual SciencesBeijing 100730China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for stem Cell and Regenerative Medicine Beijing 100101China Institute for stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Department of Neurosurgery Peking University Third HospitalCenter for Precision Neurosurgery and Oncology of Peking University Health Science CenterBeijing 100191China Spencer Center for Vision Research Byers Eye InstituteSchool of MedicineStanford UniversityPalo AltoCA 94304USA

The progressive degradation in the trabecular meshwork(TM)is related to age-related ocular diseases like primary open-angle ***,the molecular basis and biological significance of the aging process in TM have not been fully ***,we established a dynamic single-cell transcriptomic landscape of aged macaque TM,wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM ***,we divided TM cells into 13 clusters and performed an in-depth analysis on cluster O,which had the highest aging score and the most significant changes in cell proportions between the two ***,we found that the APOE gene was an important differentially expressed gene in cluster O during the aging process,highlighting the close relationship between cell migration and extracellular matrix regulation,and TM *** work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components,thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal *** work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

关键词： single-cell transcriptomic atlas macaque trabecular meshwork ocular outflow tissue aging

Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

The gut–liver axis calibrates PEDF production for ISC homeostasis

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Biophysics Reports 2024年第3期10卷 175-177页

作者： Ying Huang Xinran Wang Lulu Sun State Key Laboratory of Female Fertility Promotion Department of Endocrinology and Metabolism Peking University Third Hospital Institute of Advanced clinical Medicine Peking University

The biliary tract, portal vein, and systemic circulation are the anatomical linkages that enable bidirectional inter-organ communications through the gut–liver axis.(Han et al. 2023). Under physiological conditions, the proliferation of intestinal stem cells(ISCs) materializes the self-renewal of the intestinal epithelium for gut barrier integrity(van der Flier and Clevers 2009), and such crosstalk contributes to the repair capacity of the intestinal tract by accommodating the ISCs(Chen et al.2022; Hegyi et al. 2018). Nonetheless, in pathological conditions such as inflammatory bowel disease(IBD),the compromised intestinal barrier caused by inflammation increases the translocation of microorganisms(Wigg et al. 2001).

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Fabrication and characterisation of random and aligned electrospun scaffolds to investigate hypothalamic stem/progenitor cell behaviour

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Engineered Regeneration 2024年第1期5卷 11-20页

作者： Selina Beal Iain Stewart Paul Hatton Marysia placzek Ilida Ortega School of clinical Dentistry and Insigneo Institute Claremont CrescentUniversity of SheffieldSheffield S102TAUK School of Biosciences University of SheffieldEnglandUK National Heart and Lung Institute Imperial CollegeLondon SW36LYUK

Tanycytes are stem/progenitor cells that reside in the hypothalamus of the adult vertebrate *** can be cultured as free-floating neurospheres in vitro but tend to spontaneously differentiate over *** we asked whether morphological cues provided by engineered polymer scaffolds can modify spontaneous ***-derived neurospheres were cultured on electrospun scaffolds,prepared with either random or aligned fiber *** dispersed widely on the scaffolds,and-on aligned scaffolds-were highly organized,orientated parallel to the *** analysis showed that cells cultured on aligned scaffolds showed significantly greater expression of the neural stem/progenitor cell marker,NrCAM and reduced expres-sion of differentiated cell markers in comparison to those cultured on random *** this shows that tanycytes respond to local engineered cues,and that a morphologically constrained environment can better main-tain tanycytes as stem *** aligned scaffold culture system provides a powerful tool to better investigate this novel stem/progenitor cell population.

关键词： Scaffold Tanycytes Neural stem/progenitor cells Fiber alignment Electrospinning

The role and applications of extracellular vesicles in osteoporosis

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Bone Research 2024年第1期12卷 62-77页

作者： Fei Fang Jie Yang Jiahe Wang Tiantian Li Erxiang Wang Demao Zhang Xiaoheng Liu Chenchen Zhou Institute of Biomedical Engineering West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture,which increases patient susceptibility to fragile *** intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles(EVs),which play crucial roles in both pathological and physiological *** derived from various sources exert distinct effects on ***,EVs released by osteoblasts,endothelial cells,myocytes,and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins,miRNAs,and ***,EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone ***,the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is ***,we review the current understanding of the impact of EVs on bone homeostasis,including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in ***,we present an overview of the latest research progress on diagnosing and treating osteoporosis by using ***,we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

关键词： osteoporosis homeostasis biomaterials

维普期刊数据库

XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu Yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-Ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen Yi Zhang Jing-Ting Jiang Xiu-Bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

Embryonic stem cell-derived extracellular vesicles rejuvenate senescent cells and antagonize aging in mice

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Bioactive Materials 2023年第11期29卷 85-97页

作者： Lu Yu Hang Wen Chang Liu Chen Wang Huaxin Yu Kaiyue Zhang Qingsheng Han Yue Liu Zhongchao Han Zongjin Li Na Liu School of Medicine Nankai UniversityTianjin300071China Key Laboratory of Bioactive Materials Ministry of EducationCollege of Life Sciences Nankai UniversityTianjin300071China Institute of stem cells Health-Biotech(Tianjin)Stem Cell Research Institute Co.LtdTianjin301700China

Aging is a degenerative process that leads to tissue dysfunction and *** stem cells(ESCs)have great therapeutic potential for age-related diseases due to their capacity for self-renewal and ***,the use of ESCs in clinical treatment is limited by immune rejection,tumourigenicity and ethical ***-derived extracellular vesicles(EVs)may provide therapeutic effects that are comparable to those of ESCs while avoiding unwanted ***,we fully evaluate the role of ESC-EVs in rejuvenation in vitro and in *** RNA sequencing(RNA-Seq)and microRNA sequencing(miRNA-Seq)screening,we found that miR-15b-5p and miR-290a-5p were highly enriched in ESC-EVs,and induced rejuvenation by silencing the Ccn2-mediated AKT/mTOR *** results demonstrate that miR-15b-5p and miR-290a-5p function as potent activators of rejuvenation mediated by *** rejuvenating effect of ESC-EVs was further investigated in vivo by injection into aged *** results showed that ESC-EVs successfully ameliorated the pathological age-related phenotypes and rescued the transcriptome profile of aged *** findings demonstrate that ESC-EVs treatment can rejuvenate senescence both in vitro and in vivo and suggest the therapeutic potential of ESC-EVs as a novel cell-free alternative to ESCs for age-related diseases.

关键词： treatment aging finding