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Stem cells for spinal cord injuries bearing translational potential

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Neural Regeneration Research 2018年第1期13卷 35-42页

作者： Kyriakos Dalamagkas magdalini Tsintou alexander m.seifalian Department of Tissue Engineering Harvard Medical School Nanotechnology & Regenerative medicine Centre Division of Surgery and Interventional Science University College London Nanotechnology & Regenerative medicine Commercialisation Centre (Ltd). The London Bio Science Innovation Centre

Spinal cord injury （SCI） is a highly debilitating neurological disease, which still lacks effective treatment strategies, causing significant financial burden and distress to the affected families. Nevertheless, nanotechnology and regenerative medicine strategies holding promise for the development of novel therapies that would reach from bench to bedside to serve the SCI patients. There has already been significant progress in the field of cell-based therapies, with the clinical application for SCI, currently in phase II of the clinical trial. Stem cells （e.g., induced pluripotent stem cells, fetal stem cells, human embryonic stem cells, and olfactory ensheathing cells） are certainly not to be considered the panacea for neural repair but, especially when combined with rehabilitation or other combinatorial approaches using the help of nanotechnology, they seem to be the source of some of the most promising and clinical translatable cell-based therapies that could help solving impactful problems on neural repair.

关键词： spinal cord injury stem cells neuroregeneration plasticity repair

Control of stem cell fate by engineering their micro and nanoenvironment

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World Journal of Stem Cells 2015年第1期7卷 37-50页

作者： michelle F Griffin Peter E Butler alexander m seifalian Deepak m Kalaskar UCL Division of Surgery and Interventional Science Centre for Nanotechnology and Regenerative Medicine University College London London NW3 2PF United Kingdom Department of Plastic and Reconstructive Surgery Royal Free Hampstead NHS Trust Hospital London NW3 2PF United Kingdom

Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix(ECm) in vivo have shown to regulate stem cell differentiation. The delivery of ECm components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine.

关键词： Biomaterials Scaffold Stem cells Surfacetopography Tissue engineering

Pyrrolidine dithiocarbamate reduces ischemia-reperfusion injury of the small intestine

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World Journal of Gastroenterology 2005年第46期11卷 7308-7313页

作者： Ismail H mallick Wen-Xuan Yang marc C Winslet alexander m seifalian GI and Hepatobiliary Research Unit University Department of Surgery Royal Free and University College Medical School University College London LondonUnited Kingdom Department of Surgery Royal Free Hospital Hampstead NHS Trust London United Kingdom

AIm: To evaluate whether pyrrolidine dithiocarbamate (PDTC), an enhancer of HO production, attenuates intestinal IR ***: Eighteen male rats were randomly allocated into three groups: (a) sham; (b) IR, consisting of 30 min of intestinal ischemia, followed by 2-h period of reperfusion; and (c) PDTC treatment before IR. Intestinal microvascular perfusion (ImP) was monitored continuously by laser Doppler fiowmetry. At the end of the reperfusion, serum samples for lactate dehydrogenase (LDH) levels and biopsies of ileum were obtained. HO activity in the ileum was assessed at the end of the reperfusion ***: At the end of the reperfusion in the IR group,ImP recovered partially to 42.5% of baseline (Pm), whereas PDTC improved ImP to 67.3% of baseline (Pmpared to IR (842.3±85.12) (Pmpared to IR group (1 973.8±306.5). Histological examination showed that the ileal mucosa was significantly less injured in PDTC group as compared with IR ***: Our study demonstrates that PDTC improves the ImP and attenuates IR injury of the intestine possibly via HO production. Additional studies are warranted to evaluate the clinical efficacy of PDTC in the prevention of IR injury of the small intestine.

关键词：氮杂戊环四氢化吡咯缺血再灌注损伤小肠疾病

The olfactory system of Pieris brassicae caterpllars:from receptors to glomeruli

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Insect Science 2024年第2期31卷 469-488页

作者： Qi Wang Hans m.Smid marcel Dicke alexander Haverkamp Laboratory of Entomology Wageningen University and ResearchWageningenthe Netherlands

Tolfactory system of adult lepidopterans is among the best described neuronal ***,comparatively little is known about the organization of the olfactory system in the larval stage of these ***,we explore the expression of olfactory receptors and the organization of olfactory sensory neurons in caterpillars of Pieris brassicae,a significant pest species in Europe and a well-studied species for its chemical *** describe the larval olfactory system in this species,we first analyzed the head transcriptome of third-instar larvae(L3)and identified 16 odorant receptors(ORs)including the OR coreceptor(Orco),13 ionotropic receptors(IRs),and 8 gustatory receptors(GRs).We then quantified the expression of these 16 ORs in different life stages,using qPCR,and found that the majority of ORs had significantly higher expression in the L4 stage than in the L3 and L5 stages,indicating that the larval olfactory system is not static throughout caterpillar *** an Orco-specific antibody,we identified all olfactory receptor neurons(ORNs)expressing the Orco protein in L3,L4,and L5 caterpillars and found a total of 34 Orco-positive ORNs,distributed among three sensilla on the *** number of Orco-positive ORNs did not differ among the three larval ***,we used retrograde axon tracing of the antennal nerve and identified a mean of 15 glomeruli in the larval antennal center(LAC),suggesting that the caterpillar olfactory system follows a similar design as the adult olfactory system,although with a lower numerical *** together,our results provide a detailed analysis of the larval olfactory neurons in P brassicae,highlighting both the differences as well as the commonalities with the adult olfactory *** findings contribute to a better understanding of the development of the olfactory system in insects and its life-stage-specific adaptations.

关键词： glomeruli larvae Lepidoptera odorant receptor olfactory receptor neurons sensilla

Haemoxygenase modulates cytokine induced neutrophil chemoattractant in hepatic ischemia reperfusion injury

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World Journal of Gastroenterology 2016年第33期22卷 7518-7535页

作者： Niteen Tapuria Sameer Junnarkar mahmoud Abu-amara Barry Fuller alexander m seifalian Brian R Davidson Department of HPB Surgery and Liver transplantation Royal Free Hospital

AIm To investigate the hepatic microcirculatory changes due to Haemoxygenase(HO),effect of HO inhibition on remote ischemic preconditioning(RIPC) and modulation of *** Eight groups of animals were studied- Sham,ischemia reperfusion injury(IRI) the animals were subjected to 45 min of hepatic ischemia followed by three hours of reperfusion,RIPC(remote ischemic preconditioning) + IRI group,remote ischemic preconditioning in sham(RIPC + Sham),PDTC + IR(Pyridodithiocarbamate,HO donor),Zn PP + RIPC + IRI(Zinc protoporphyrin prior to preconditioning),IR-24(45 min of ischemia followed by 24 h of reperfusion),RIPC+IR-24(preconditioning prior to. After 3 and 24 h of reperfusion the animals were killed by exsanguination and samples were taken. RESULTS Velocity of flow(160.83 ± 12.24 μm/s),sinusoidal flow(8.42 ± 1.19) and sinusoidal perfusion index(42.12 ± 7.28) in hepatic IR were lower(P mparison to RIPC and PDTC(HO inducer). RIPC increased velocity of flow(328.04 ± 19.13 μm/s),sinusoidal flow(17.75 ± 2.59) and the sinusoidal perfusion index(67.28 ± 1.82)(P m/s),sinusoidal flow(17.66 ± 3.71) and sinusoidal perfusion(82.33 ± 3.5) to near sham levels. Zn PP(HO inhibition) reduced velocity of flow of RBC in the RIPC group(170.74 ± 13.43 μm/s and sinusoidal flow in the RIPC group(9.46 ± 1.34). Zn PP in RIPC(60.29 ± 1.82) showed a fall in perfusion only at 180 min of reperfusion. Neutrophil adhesion in IR injury is seen in both postsinusoidal venules(769.05 ± 87.48) and sinusoids(97.4 ± 7.49). Neutrophil adhesion in RIPC + IR injury is reduced in both postsinusoidal venules(219.66 ± 93.79) and sinusoids(25.69 ± 9.08)(P < 0.05). PDTC reduced neutrophil adhesion in both postsinusoidal venules(89.58 ± 58.32) and sinusoids(17.98 ± 11.01)(P < 0.05) reproducing the effects of RIPC. Zn PP(HO inhibition) increased venular(589.04 ± 144.36) and sinusoida

关键词： Reperfusion injury CINC microcirculation Ischaemic preconditioning Remote preconditioning Haemoxygenase

Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells

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World Journal of Stem Cells 2015年第2期7卷 266-280页

作者： Shima Salmasi Deepak m Kalaskar Wai-Weng Yoon Gordon W Blunn alexander m seifalian UCL Division of Surgery and Interventional Science Centre for Nanotechnology and Regenerative MedicineUniversity College London Royal National Orthopaedic Hospital Institute of Orthopaedics and musculoSkeletal Science University College London Institute of Orthopaedics and musculoSkeletal Science Royal National Orthopaedic Hospital

Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional(3D) organs, such as bone, skin, liver, kidney and ear,using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nanosurface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.

关键词： Nanotopography mesenchymal stem cells Tissue engineering Nanotechnology Three dimensionalorgans/tissues Scaffolds

Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

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Bone Research 2024年第1期12卷 180-198页

作者： morten S.Hansen Kaja madsen maria Price Kent Søe Yasunori Omata mario m.Zaiss Caroline m.Gorvin morten Frost alexander Rauch molecular Endocrinology Laboratory(KmEB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of metabolism and Systems Research(ImSR)and Centre for Diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for membrane Proteins and Receptors(COmPARE) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of molecular medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic Surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany Steno Diabetes Center Odense Odense University HospitalDK-5000 Odense CDenmark

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

Praseodymium metal nanorods as a 5-fluorouracil carrier

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Journal of Rare Earths 2024年第7期42卷 1328-1336,I0005页

作者： Varnitha manikantan Govindaraj Sri Varalakshmi Ujma Ashapak Tamboli Archana Sumohan Pillai Aleyamma alexander Anushka Lucas Bose Allben Akash Israel V.m.V.Enoch Centre for Nanoscience and Genomics Karunya Institute of Technology and Sciences(Deemed University)Coimbatore641114Tamil NaduIndia Department of Applied Chemistry Karunya Institute of Technology and Sciences(Deemed University)Coimbatore641114Tamil NaduIndia

Interest in metal nanoparticles as nanoscale drug-carrying vehicles has been *** such an aspect,lanthanide metal nanoparticles are particularly ***,we report praseodymium nanoparticles as a novel anticancer therapeutic transporting *** material was made as a composite with the supramolecular host polymer,poly-β-*** praseodymium nanorods were characterized using standard analytical techniques,including X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and thermogravimetric analysis(TGA).In addition,they were imaged using transmission electron *** nanostructures are a long rod-shaped material with 2.0±0.1μm in length and 230±10 nm in *** material shows a saturation magnetization value above 30 emu/g with a coercivity value of 130 *** nanocarrier is freighted with the drug 5-fluorouracil,and the encapsulation efficiency is 76.09%.The drug release is continuous from the nanocarrier(polymer-containing praseodymium nanoparticles)and proceeds for above 250 *** in vitro cytotoxicities of the blank nanocarrier and the 5-fluorouracil-loaded one are deduced by testing them on mCF-7 and Vero(non-cancerous)cell *** cytotoxicity on the cancerous cell lines is observed,whereas the non-cancerous cells are *** IC_(50)values on the cell lines are reported.

关键词： metal nanoparticles Praseodymium Poly-cyclodextrin Drug delivery Anticancer activity Rare earths

New Opportunities for Neutrons in Environmental and Biological Sciences

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Frontiers of Environmental Science & Engineering 2024年第7期18卷 179-186页

作者： alexander Johs Shuo Qian Leighton Coates Brian H.Davison James G.Elkins Xin Gu Jennifer morrell-Falvey Hugh O'Neill Jeffrey m.Warren Eric m.Pierce Kenneth Herwig Oak Ridge National Laboratory Oak RidgeTN37831USA

The use of neutron methods in environmental and biological sciences is rapidly emerging and accelerating with the development of new instruments at neutron user *** article,based on a workshop held at Oak Ridge National Laboratory(ORNL),offers insights into the application of neutron techniques in environmental and biological *** highlight recent advances and identify key challenges and potential future research *** include soil and rhizosphere processes,root water dynamics,plant-microbe interactions,structure and dynamics of biological systems,applications in synthetic biology and enzyme engineering,next-generation bioproducts,biomaterials and bioenergy,nanoscale structure,and fluid dynamics of porous materials in *** provide an outlook on emerging opportunities with an emphasis on new capabilities that will be enabled at the Spallation Neutron Source Second Target Station currently under design at *** mission of scientific neutron user facilities worldwide is to enable science using state-of-the-art neutron *** aim to encourage researchers in the environmental and biological research community to explore the unique capability afforded by neutrons at these facilities.

关键词： Neutrons Environment Biology Neutron imaging Neutron scattering Second Target Station(STS)