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Periosteum derived stem cells for regenerative medicine proposals: boosting current knowledge

World Journal of Stem Cells 2014年第3期6卷 266-277页

作者： Concetta Ferretti monica mattioli-belmonte Department of Clinical and Molecular Sciences School of Medicine Università Politecnica delle Marche

Periosteum is a thin fibrous layer that covers most bones. It resides in a dynamic mechanically loaded environment and provides a niche for pluripotent cells and a source for molecular factors that modulate cell behaviour. Elucidating periosteum regenerative poten-tial has become a hot topic in orthopaedics. This review discusses the state of the art of osteochondral tissue engineering rested on periosteum derived progenitor cells(PDPCs) and suggests upcoming research direc-tions. Periosteal cells isolation, characterization and migration in the site of injury, as well as their differen-tiation, are analysed. Moreover, the role of cell mecha-nosensing and its contribution to matrix organization, bone microarchitecture and bone stenght is examined. In this regard the role of periostin and its upregulation under mechanical stress in order to preserve PDPC sur-vival and bone tissue integrity is contemplated. The re-view also summarized the role of the periosteum in the field of dentistry and maxillofacial reconstruction. The involvement of microRNAs in osteoblast differentiation and in endogenous tissue repair is explored as well. Fi-nally the novel concept of a guided bone regenerationbased on the use of periosteum itself as a smart mate-rial and the realization of constructs able to mimic the extracellular matrix features is talked out. Additionally, since periosteum can differentiate into insulin produc-ing cells it could be a suitable source in allogenic trans-plantations. That innovative applications would takeadvantage from investigations aimed to assess PDPCimmune privilege.

关键词： Periosteum Mesenchymal stem cells Mi-croRNA Bone tissue engineering Bone turn-over

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Morphological Evaluation of Adhesion and Proliferation of Osteoblast Like Cells Grown on Gelatin/Genipin Scaffold

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Journal of Life Sciences 2013年第9期7卷 965-970页

作者： Gabriella Teti Adriana Bigi monica mattioli-belmonte Roberto Giardino Milena Fini Antonio Mazzotti Mirella Falconi Department of Biomedical and Neuromotor Sciences University of Bologna Bologna 40126 Italy Department of Chemistry "G. Ciamician" University of Bologna Bologna 40126 Italy Department of Clinical and Molecular Sciences Universita Politecnica delle Marche Ancona 60121 Italy Laboratory of Preclinical Surgical Studies Rizzoli Orthopaedic Institute Bologna 40136 Italy Rizzoli Orthopaedic Institute IRCCS Bologna 40136 Italy

This work focusing on studying the biocompatibility and the effect of gelatin porous scaffold on the characteristics of human osteoblast like cells, including proliferation, adhesion, scaffold-cell interaction and its potential to induce bone regeneration. Osteoblast like cells were seeded on gelatin/genipin scaffolds for 7, 14 and 21 days. Cell proliferation assay, light microscopy, transmission electron microscopy and high resolution scanning electron microscopy were carried to evaluate cell viability, cell adhesion and the production of extracellular matrix. Cell proliferation assay showed a high biocompatibility of the material. High resolution scanning electron microscopy and light microscopy showed a strong adhesion of MG63 ceils on the surface of gelatin scaffold and high penetration in the macroporosities of the material. TEM analysis showed an intense production of extracellular matrix protein. In vitro analysis indicated a good biocompatibility of the scaffold and presents it as a potential candidate material for tissue engineering.

关键词： 3D gelatine scaffold scaffold adhesion extracellular matrix biocompatibility electron microscopy

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Cytotoxicity of a silorane-based dental composite on human gingival fibroblasts

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World Journal of Stomatology 2013年第4期2卷 86-90页

作者： Giovanna Orsini Alberto Catellani Concetta Ferretti Marco Gesi monica mattioli-belmonte Angelo Putignano Department of Clinical Sciences and Stomatology Polytechnic University of Marche66020 AnconaItaly Department of Clinical and Molecular Sciences Polytechnic University of Marche66020 AnconaItaly Department of Translational Research and New Technology in Medicine and Surgery University of Pisa56126 PisaItaly

AIM:To evaluate the direct and indirect biocompatibility of Filtek Silorane on human gingival fibroblastic ***:Sixty-three standardized cylindrical specimens(8 mm diameter and 2 mm thickness)of restorative material were prepared using a light emitting diode-curing *** sample were built up in one increment and divided in 2 *** the first group,21samples(unpolished samples)were left without a specific polishing procedure;in the second one,42 samples(polished samples)were polished with 4 different grains of *** cultures,obtained from gingiva of 2 subjects without systemic and oral disease,were used to assess the direct and indirect *** cultured for 48 h in normal culture medium were used as a ***:The scanning electron microscope observations of fibroblasts cultured on the silorane samples,either polished or unpolished,confirmed the good biocompatibility of the material,favouring the cellular spreading.3-dimethylthiazol-2,5-diphenyltetrazolium bromide tests showed a significant reduction(P<0.01)of gingival fibroblasts viability cultured both in polished samples(90.05%±19.00%)and unpolished samples(78.15%±11.00%)compared with the *** growth in medium conditioned with the samples for 1 wk showed a significant viability reduction(P<0.01)compared to the control.A reduction of cell viability was observed even in the groups containing the material for 3 wk(polished:89.45%±10.00%;unpolished:65.97%±10.00%),even if the cytotoxicity was reduced after this long time ***:Although the poor chromatic availability of this material remains a big limit that restricts its use to posterior sectors,the silorane-based material can be considered an option to perform restorations when aesthetic demands are not the priority,such as the

关键词： Silorane Cytotoxicity Resin composite Fibroblasts

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Empagliflozin reduces brain pathology in Alzheimer's disease and type 2 diabetes

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Neural Regeneration Research 2024年第6期19卷 1189-1190页

作者： Carmen Hierro-Bujalance monica Garcia-Alloza Division of Physiology School of MedicineUniversidad de CadizCadizSpain Instituto de Investigacion e Innovacion en Ciencias Biomedicas de la Provincia de Cadiz(INIBICA) CadizSpain Salus Infirmorum-Universidad de Cadiz CadizSpain

Alzheimer's disease(AD)and type 2 diabetes(T2D):More than 55 million people suffer from dementia,and it is expected that over 150 million people will suffer from this disease by *** is the most common type of dementia and while aging remains the main risk factor to suffer it,previous studies have also shown that metabolic disorders,and T2D specifically,are also major contributors(Wang et al.,2012).

关键词： Alzheimer diabetes

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Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

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Neural Regeneration Research 2025年第5期20卷 1409-1410页

作者： Rafael Lujan Alejandro Martín-belmonte Sergi Ferré Francisco Ciruela Synaptic Structure Laboratory Instituto de Biomedicina de la UCLM(IB-UCLM)Departamento de Ciencias MédicasInstituto de Investigación en Salud de Castilla-La Mancha(IDISCAM)Facultad de MedicinaUniversidad Castilla-La ManchaCampus BiosanitarioC/AlmansaAlbaceteSpain Integrative Neurobiology Section National Institute on Drug AbuseIntramural Research ProgramNational Institutes of HealthBaltimoreMDUSA Pharmacology Unit Department of Pathology and Experimental TherapeuticsSchool of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaNeuropharmacology&Pain GroupNeuroscience ProgramBellvitge Institute for Biomedical ResearchL’Hospitalet de LlobregatSpain

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic *** has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

关键词： Alzheimer pathology

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A review of ethnobotanical studies reveals over 500 medicinal plants in Mindanao,Philippines

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Plant Diversity 2024年第5期46卷 551-564页

作者： Joeime F.Meñiza monica M.Pasco Jemer A.Alimbon Department of Teacher Education UM Tagum CollegeTagum City8100Davao del Norte Philippines

Medicinal plants have long been used to treat various diseases in both indigenous and non-indigenous populations of Mindanao,***,we extracted data from ethnobotanical studies to compile a comprehensive list of these medicinal plants and identify how and for what purpose they are most commonly *** identified 530 verified medicinal plant species across 372 genera in 118 *** two most frequently cited species were Euphorbia hirta and Psidium *** most represented family was Fabaceae and the most represented genus was Ficus.A total of 28 medicinal plant species are designated as threatened at the national or global level;of these,11 are endemic to the *** plant preparations most commonly use leaves for oral administration to treat various diseases such as digestive issues,including *** study underscores the need for further ethnobotanical investigations,particularly in areas lacking *** also emphasizes the need for conservation of threatened and endemic medicinal plants to ensure sustainable utilization of this valuable resource.

关键词： Ethnobotany Medicinal plants Mindanao Philippines

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Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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Resilience to structural and molecular changes in excitatory synapses in the hippocampus contributes to cognitive function recovery in Tg2576 mice

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Neural Regeneration Research 2024年第9期19卷 2068-2074页

作者： Carolina Aguado Sara Badesso JoséMartínez-Hernández Alejandro Martín-belmonte Rocío Alfaro-Ruiz Miriam Fernández Ana Esther Moreno-Martínez Mar Cuadrado-Tejedor Ana García-Osta Rafael Luján Synaptic Structure Laboratory Instituto de Investigación en Discapacidades Neurológicas(IDINE)Department of Medical SciencesFacultad de MedicinaUniversidad de Castilla-La ManchaCampus BiosanitarioAlbaceteSpain Gene Therapy for Neurological Disease Program Center for Applied Medical Research(CIMA)University of NavarraInstituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Pharmacology Unit Department of Pathology and Experimental TherapeuticsFaculty of Medicine and Health SciencesInstitute of NeurosciencesUniversity of BarcelonaBarcelonaSpain Neuropharmacology and Pain Group Neuroscience ProgramInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatSpain Department of Pathology Anatomy and PhysiologySchool of MedicineUniversity of NavarraPamplonaSpain UniversitéGrenoble Alpes Grenoble Institut des NeurosciencesGrenobleFrance

Plaques of amyloid-β(Aβ)and neurofibrillary tangles are the main pathological characteristics of Alzheimer’s disease(AD).However,some older adult people with AD pathological hallmarks can retain cognitive *** the factors that lead to this cognitive resilience to AD offers promising prospects for identifying new therapeutic *** hypothesis focuses on the contribution of resilience to changes in excitatory synapses at the structural and molecular levels,which may underlie healthy cognitive performance in aged AD *** the Morris Water Maze test,we selected resilient(asymptomatic)and cognitively impaired aged Tg2576 *** the enzyme-linked immunosorbent assay showed similar levels of Aβ42 in both experimental groups,western blot analysis revealed differences in tau pathology in the pre-synaptic supernatant *** further investigate the density of synapses in the hippocampus of 16-18 month-old Tg2576 mice,we employed stereological and electron microscopic *** findings indicated a decrease in the density of excitatory synapses in the stratum radiatum of the hippocampal CA1 in cognitively impaired Tg2576 mice compared with age-matched resilient Tg2576 and non-transgenic ***,through quantitative immunoelectron microscopy in the hippocampus of impaired and resilient Tg2576 transgenic AD mice,we uncovered differences in the subcellular localization of glutamate ***,the density of GluA1,GluA2/3,and mGlu5 in spines and dendritic shafts of CA1 pyramidal cells in impaired Tg2576 mice was significantly reduced compared with age-matched resilient Tg2576 and non-transgenic ***,the density of GluA2/3 in resilient Tg2576 mice was significantly increased in spines but not in dendritic shafts compared with impaired Tg2576 and non-transgenic *** subcellular findings strongly support the hypothesis that dendritic spine plasticity and synaptic machinery in the hippocampus play cr

关键词： aging Alzheimer´s disease cognitive hippocampus immunoelectron microscopy resilience synapse

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A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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Protein & Cell 2024年第2期15卷 98-120页

作者： Shanshan Yang Chengyu Liu Mengmeng Jiang Xiaoqian Liu Lingling Geng Yiyuan Zhang Shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua belmonte Weiqi Zhang Jing Qu Guang-Hui Liu Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Xuanwu Hospital Capital Medical University Beijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Aging Biomarker Consortium Beijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related ***,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ***,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche *** in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during *** particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular *** study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

关键词： single-nucleus RNA sequencing liver hepatocytes aging senescence SREBP2

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Resampling approaches for the quantitative analysis of spatially distributed cells

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Data Intelligence 2024年第1期6卷 104-119页

作者： Giorgio Bertolazzi Michele Tumminello Gaia Morello Beatrice belmonte Claudio Tripodo Department of Economics Business and StatisticsUniversity of PalermoPalermoItaly Tumor Immunology Unit Department of Health SciencesUniversity of PalermoPalermoItaly Histopathology Unit Institute of Molecular Oncology Foundation(IFOM)ETS-The AIRC Institute of Molecular OncologyMilanItaly

Image segmentation is a crucial step in various image analysis pipelines and constitutes one of the cutting-edge areas of digital *** advent of quantitative analysis has enabled the evaluation of millions of individual cells in tissues,allowing for the combined assessment of morphological features,biomarker expression,and spatial *** recorded cells can be described as a point pattern ***,the classical statistical approaches to point pattern processes prove unreliable in this context due to the presence of multiple irregularly-shaped interstitial cell-devoid spaces in the domain,which correspond to anatomical features(***,lipid vacuoles,glandular lumina)or tissue artefacts(*** fractures),and whose coordinates are *** interstitial spaces impede the accurate calculation of the domain area,resulting in biased clustering ***,the mistaken inclusion of empty regions of the domain can directly impact the results of hypothesis *** literature currently lacks any introduced bias correction method to address interstitial cell-devoid *** address this gap,we propose novel resampling methods for testing spatial randomness and evaluating relationships among different cell *** methods obviate the need for domain area estimation and provide non-biased clustering *** created the SpaceR software(https://***/GBertolazzi/SpaceR)to enhance the accessibility of our methodologies.

关键词： Digital pathology spatial cytometry spatial clustering spatial randomness resampling

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