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World Journal of Stem cells 2024年第5期16卷 462-466页

作者： Zhen Xiang Rui-Peng Cai Yang Xiao Yong-Can Huang Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies Department of Spine SurgeryPeking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina Department of Breast and Thyroid Surgery Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina

Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.

关键词： Single-cell sequencing Diabetic wound healing Cell subpopulations Heterogeneity Pathogenesis progenitor cells

Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis

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World Journal of Gastroenterology 2010年第2期16卷 217-224页

作者： Ursula M Gehling Marc Willems Kathleen Schlagner Ralf A Benndorf Maura Dandri Jrg Petersen Martina Sterneck Joerg-Matthias Pollok Dieter K Hossfeld Xavier Rogiers Department of Hepatobiliary Surgery and Transplant Surgery University Hospital Hamburg-Eppendorf20246 HamburgGermany Department of Medicine University Hospital Hamburg-Eppendorf20246 HamburgGermany Institute of Experimental and Clinical Pharmacology and Toxicology University Hospital Hamburg-Eppendorf20246 HamburgGermany Gent University Hospital and Medical School 9000 GentBelgium

AIM:To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells. METHODS:Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry.Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1(SDF-1) were measured using an enzyme linked immunosorbent assay.RESULTS:progenitor cells with a CD133 + /CD45 + CD14 + phenotype were observed in 61%of th patients.Between 1%and 26%of the peripheral bloo mononuclear cells(MNCs)displayed this phenotype Furthermore,a distinct population of c-kit + progenito cells(between 1%and 38%of the MNCs)could b detected in 91%of the patients.Additionally,18% of the patients showed a population of progenito cells(between 1%and 68%of the MNCs)that wa characterized by expression of breast cancer resistanc protein-1.Further phenotypic analysis disclosed tha the circulating precursors expressed CXC chemokin receptor 4,the receptor for SDF-1.In line with thi finding,elevated plasma levels of SDF-1 were presen in all patients and were found to correlate with th number of mobilized CD133 + progenitor cells.

关键词： CD133 antigen CD14 antigen c-kit protein Breast cancer resistance protein-1 protein progenitor cells CXC chemokine receptor 4 Stromal cell-derived factor-1 Liver cirrhosis

Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice

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Acta Pharmacologica Sinica 2006年第11期27卷 1395-1400页

作者： Yun-feng LI~2 Hong-xia CHEN Ying LIU You-zhi ZHANG Yan-qin LIU Jin LI Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China Beijing Institute of Pharmacology and Toxicology Beijing China

Aim:To explore the mechanism of agmatine’s antidepressant action.Methods:Male mice were subjected to a variety of unpredictable stressors on a daily basisover a 24-d period.The open-field behaviors of the mice were displayed andrecorded using a Videomex-V image analytic system automatically.For bromodeo-xyuridine(BrdU;thymidine analog as a marker for dividing cells)labeling,the micewere injected with BrdU(100 mg/kg,ip,twice per d for 2 d),and the hippocampalneurogenesis in stressed mice was measured by immunohistochemistry.Theproliferation of cultured hippocampal progenitor cells from neonatal rats wasdetermined by colorimetric assay(cell counting kit-8)and ~3H-thymidine incorpo-ration assay.Results:After the onset of chronic stress,the locomotor activity ofthe mice in the open field significantly decreased,while coadministration of agma-tine 10 mg/kg(po)blocked it.Furthermore,the number of BrdU-labeled cells in thehippocampal dentate gyrus significantly decreased in chronically stressed mice,which was also blocked by chronic coadministration with agmatine 10 mg/kg(po).Four weeks after the BrdU injection,some of the new born cells matured andbecame neurons,as determined by double labeling for BrdU and neuron specificenolase(NSE),a marker for mature neurons.In vitro treatment with agmatine 0.1-10 μmol/L for 3 d significantly increased the proliferation of the cultured hippoc-ampal progenitor cells in a dose-dependent manner.Conclusion:We have foundthat agmatine increases proliferation of hippocampal progenitor cells in vitro andthe hippocampal neurogenesis in vivo in chronically stressed mice,This may beone of the important mechanisms involved in agmatine’s antidepressant action.

关键词： Agmatine antidepressant neurogenesis chronic stress hippocampus progenitor cells

Biological properties of neural progenitor cells isolated from the hippocampus of adult cynomolgus monkeys

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Chinese Medical Journal 2006年第2期119卷 110-116页

作者： YUE Feng CHEN Biao WU Di DONG Kai ZENG Si-en ZHANG Yu Department of Neurology Beijing Institute of Geriatrics Xuanwu Hospital Capital University of Medical Science and Key Laboratory of Neurodegeneration Ministry of Education Beijing 100053 China Cell Therapy Center Beijing Institute of Geriatrics Xuanwu Hospital Capital University of Medical Science and Key Laboratory of Neurodegeneration Ministry of Education Beijing 100053 China Department of Pathology Guilin Medical College Guilin 541001 China

Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPCs） from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-β Ⅲ-tubulin （Tuj1） and 84% expressed astrocyte specific marker-fibrillary acidic protein （GFAP）. In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.

关键词： stem cells progenitor cells cell differentiation hippocampus primates adult

Stem/progenitor cells in fetuses and newborns:overview of immunohistochemical markers

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Cell Regeneration 2021年第1期10卷 239-250页

作者： D.Fanni C.Gerosa C.Loddo M.Castagnola V.Fanos M.Zaffanello G.Faa Division of Pathology University Hospital San Giovanni Di Diovia Ospedale54CagliariItaly Department of Biology College of Science and TechnologyTemple UniversityPhidelphiaUSA Neonatal Intensive Care Unit Department of Surgical SciencesUniversity of CagliariCagliariItaly Laboratory of Biochemistry and Metabolomics IRCCS Fondazione Santa LuciaRomeItaly Department of Surgical Sciences DentistryGynecology and PediatricsUniversity of VeronaPiazzale Stefani1I-37126 VeronaItaly

Microanatomy of the vast majority of human organs at birth is characterized by marked differences as compared toadult organs, regarding their architecture and the cell types detectable at histology. In preterm neonates, thesedifferences are even more evident, due to the lower level of organ maturation and to ongoing cell differentiation.One of the most remarkable finding in preterm tissues is the presence of huge amounts of stem/progenitor cells inmultiple organs, including kidney, brain, heart, adrenals, and lungs. In other organs, such as liver, the completelydifferent burden of cell types in preterm infants is mainly related to the different function of the liver duringgestation, mainly focused on hematopoiesis, a function that is taken by bone marrow after birth. Our preliminarystudies showed that the antigens expressed by stem/progenitors differ significantly from one organ to the next.Moreover, within each developing human tissue, reactivity for different stem cell markers also changes duringgestation, according with the multiple differentiation steps encountered by each progenitor during development. Abetter knowledge of stem/progenitor cells of preterms will allow neonatologists to boost preterm organmaturation, favoring the differentiation of the multiple cells types that characterize each organ in at term neonates.

关键词： Fetus Immunohistochemical analysis Newborn progenitor cells Stem cells

miR-18a counteracts AKT and ERK pathway activation to inhibit the proliferation of pancreatic progenitor cells

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miR-18a counteracts AKT and ERK pathway activation to inhibi...

Enhanced external counterpulsation promotes growth cytokines-mediated myocardial angiogenesis in a porcine model of hypercholesterolemia

中国畜牧兽医学会动物解剖及组织胚胎学分会第十九次学术研...

作者： Xuyan Li Zhenwu Zhang Yunchao Li Yicheng Zhao Wenjun Zhai Lin Yang Delin Kong Chunyan Wu Chunbo Teng College of Life Science Northeast Forestry University

Activation of endogenous stem/progenitor cells to repair injured tissues is an ideal option for disease treatment.However,adult pancreatic progenitor cells remain in a quiescent state in vivo.Thus,it is difficult to stimulate proliferation and differentiation in these beta cells,and the cause remains elusive.miR-17-92 cluster miRNAs are highly conserved in mammals and are expressed in multiple tissue stem/progenitor cells,but their role in pancreatic progenitor cells are less well known.In the present study,we demonstrate that miR-18 a,but not the other members of the miR-17-92 gene cluster,inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo.miR-18 a inhibits proliferation of adult pancreatic progenitor cells through arresting the cell cycle at G1 stage,indicating that miR-18 a plays a role in keeping the adult pancreatic progenitor cells in quiescence.miR-18 a inhibits pancreatic progenitor proliferation by targeting the gene expressions of CTGF,NEDD9,and CDK19,as well as by suppressing activation of the proliferation-related signaling pathways PI3K/AKT and ERK.miR-18 a inhibitor could reverse the target gene downregulation,promote pancreatic progenitor cell entrance into the S stage,and activate the signaling pathway for proliferation.This study suggests that miR-18 inhibitor may be used to evoke endogenous pancreatic progenitor cells to cure diabetes.

关键词： miR-18a pancreas progenitor cells proliferation AKT ERK

来源： cnki会议评论

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Chinese Medical Journal 2009年第10期122卷 1188-1194页

作者： LUO Jing-yun WU Gui-fu XIONG Yan CHEN Guo-wei XIE Qiang YANG Da-ya HE Xiao-hong ZHANG Yan LIU Dong-hong WANG Kui-jian MA Hong ZHENG Zhen-sheng DU Zhi-min Division of Cardioiogy the First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China Department of Ultrasound the First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China Department of Biomedical Engineering the First Affiliated Hospital Sun Yat-sen University Guangzhou Guangdong 510080 China Division of Cardiology Guangzhou Red Cross Hospital Guangzhou Guangdong 510220 China The Key Laboratory on Assisted Circulationl the Ministry of Health Guangzhou Guangdong 510080 China

Background Enhanced external counterpulsation （EECP） improves ischemia in patients with refractory angina pectoris but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34^＋, CD29^＋, and CD106^＋. Methods Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups： normal diet （control, n=6）, hypercholesterolemic diet （CHOL, n=-6）, hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor （rhG-CSF）（rhG-CSF, n=6）, and hypercholesterolemic diet with EECP treatment （EECP, n=6）. EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor （VEGF） and granulocyte colony-stimulating factor （G-CSF）, peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor l a （SDF-1α） in porcine myocardium were assessed, respectively. Results A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 （（38.3±5.6） pg/ml at week 15 vs （26.2±3.7） pg/ml at week 12, P 〈0.05, and （46.9±6.1） pg/ml at week 18 vs （26.2±3.7） pg/ml at week 12, P 〈0.01）. The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days （（150±13.9） pg/ml at week 18 vs （24.8±5.4） pg/ml at week 12, P 〈0.01）. Compared to other groups and other time points, progenitor celt counts increased significantly after 2-hour EECP treatment （108±13 vs 26±6 per 10^5 leukocytes, P 〈0.01）, but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for f

关键词： angiogenesis atherosclerosis progenitor cells enhanced external counterpulsation shear stress swine

Central nervous system and peripheral cell labeling by vascular endothelial cadherin-driven lineage tracing in adult mice

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Neural Regeneration Research 2020年第10期15卷 1856-1866页

作者： Alejandro Soto-Avellaneda Brad E.Morrison Biomolecular Ph.D.Program Boise State UniversityBoiseIDUSA Department of Biological Sciences Boise State UniversityBoiseIDUSA

Understanding the contribution of endothelial cells to the progenitor pools of adult tissues has the potential to inform therapies for human disease.To address whether endothelial cells transdifferentiate into non-vascular cell types,we performed cell lineage tracing analysis using transgenic mice engineered to express a fluorescent marker following activation by tamoxifen in vascular endothelial cadherin promoter-expressing cells(VEcad-CreERT2;B6 Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze).Activation of target-cell labeling following 1.5 months of ad libitum feeding with tamoxifen-laden chow in 4–5 month-old mice resulted in the tracing of central nervous system and peripheral cells that include:cerebellar granule neurons,ependymal cells,skeletal myocytes,pancreatic beta cells,pancreatic acinar cells,tubular cells in the renal cortex,duodenal crypt cells,ileal crypt cells,and hair follicle stem cells.As Nestin expression has been reported in a subset of endothelial cells,Nes-CreERT2 mice were also utilized in these conditions.The tracing of cells in adult Nes-CreERT2 mice revealed the labeling of canonical progeny cell types such as hippocampal and olfactory granule neurons as well as ependymal cells.Interestingly,Nestin tracing also labeled skeletal myocytes,ileal crypt cells,and sparsely marked cerebellar granule neurons.Our findings provide support for endothelial cells as active contributors to adult tissue progenitor pools.This information could be of particular significance for the intravenous delivery of therapeutics to downstream endothelial-derived cellular targets.The animal experiments were approved by the Boise State University Institute Animal Care and Use Committee(approval No.006-AC15-018)on October 31,2018.

关键词： endothelial lineage tracing progenitor cells transdifferentiation ve-cadherin

Insights into stem cell therapy for diabetic retinopathy: a bibliometric and visual analysis

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Neural Regeneration Research 2021年第1期16卷 172-178页

作者： Xiang-Jun Li Chun-Yan Li Dan Bai Ying Leng Department of Ophthalmology Affiliated Hospital of Beihua UniversityJilinJilin ProvinceChina Department of Endocrinology Affiliated Hospital of Beihua UniversityJilinJilin ProvinceChina

Stem cells have been confirmed to be involved in the occurrence and development of diabetic retinopathy;however,the underlying mechanisms remain unclear.In this study,we used Citespace software to visually analyze 552 articles exploring the stem cell-based treatment of diabetic retinopathy over the past 20 years,which were included in the Web of Science Core Collection.We found the following:(1)a co-citation analysis of the references cited by all 552 articles indicated 15 clusters.In cluster#0,representing the stem cell field,some highly cited landmark studies emerged between 2009–2013.For example,endothelial progenitor cells and diabetic retinopathy gradually received the full attention of scholars,in terms of their relationship and therapeutic prospects.Some researchers also verified the potential of adipose-derived stem cells to differentiate into stable retinal perivascular cells,using a variety of animal models of retinal vascular disease.All of these achievements provided references for the subsequent stem cell research.(2)An analysis of popular keywords among the 552 articles revealed that,during the past 20 years,a relative increase in basic research articles examining stem cells and endothelial progenitor cells for the treatment of diabetic retinopathy was observed.The contents of these articles primarily involved the expression of vascular endothelial growth factor,vascular regeneration,oxidative stress,and inflammatory response.(3)A burst analysis of keywords used in the 552 articles indicated that genetic and cytological research regarding the promotion of angiogenesis was an issue of concern from 2001 to 2012,including several studies addressing the expression of various growth factor genes;from 2014 to 2020,mouse models of diabetic retinopathy were recognized as mature animal models,and the most recent research has focused on macular degeneration,macular edema,neurodegeneration,and inflammatory changes in diabetic animal models.(4)Globally,the current authoritative studies have focused on basic res

关键词： diabetes diabetic retinopathy epithelial cells macula progenitor cells retina stem cells visual analysis

NLR’s Analogs with Young Blood cells in Monitoring of Toxicity of Long-Term Preventing Immunosuppression in the Liver Transplant’s Recipients

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Open Journal of Biophysics 2022年第4期12卷 173-184页

作者： Aleksey N. Shoutko Olga A. Gerasimova Department of Transplantation Stem Cells of Russian Research Center of Radiology and Surgical Technologies named after A. M. Granov Saint-Petersburg Russia

The blood neutrophils to lymphocytes ratio (NLR) reflects the physiological homeostasis between lymphopoiesis and myelopoiesis, and its elevation serves as a harmful sign in many pathologies, partially, late rejection of allograft. The stem and young lymphoid cells have regenerative-trophic properties, which can affect the relevance of NLR, being opposed to immune properties, associated with bulk lymphocytes. In the present article, we have analyzed for the first time the applicability of NLR’s analogs with stem and immature blood cells for monitoring harmful long-term shifting from lymphopoiesis to myelopoiesis in transplant’s recipients received conventional immunosuppressive treatment. In opposition to conventional NLR, the ratio of subpopulation of CD31 cells committed to the liver tissue by alfa-fetoprotein (AFP), seems sensitive enough for such monitoring several years after transplantation of the liver from the dead.

关键词： Liver Transplantation Health Late Period Monitoring Stem progenitor cells NLR