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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Apolipoprotein B100 is required for hepatitis C infectivity and Mipomersen inhibits hepatitis C

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World Journal of Gastroenterology 2016年第45期22卷 9954-9965页

作者： Esperance ak Schaefer james Meixiong Christina Mark Amy Deik Daniel L Motola Dahlene Fusco Andrew Yang Cynthia Brisac Shadi Salloum Wenyu Lin Clary B Clish Lee F Peng Raymond T Chung Gastrointestinal Unit Massachusetts General Hospital Bossston MA 02114 United States Department of Medicine Harvard Medical School Bossston MA 02114 United States both of the Broad Institute of Harvard and M.I.T. Cambridge MA 02115 United States Temple University Health System Cambridge MA 02142 United States

AIM To characterize the role of apolipoprotein B100(apoB 100) in hepatitis C viral(HCV) infection. METHODS In this study, we utilize a gene editing tool, transcription activator-like effector nucleases(TALENs), to generate human hepatoma cells with a stable genetic deletion of APOB to assess of apoB in HCV. Using infectious cell culture-competent HCV, viral pseudoparticles, replicon models, and lipidomic analysis we determined the contribution of apoB to each step of the viral lifecycle. We further studied the effect of mipomersen, an FDAapproved antisense inhibitor of apoB 100, on HCV using in vitro cell-culture competent HCV and determined itsimpact on viral infectivity with the TCID50 method. RESULTS We found that apo B100 is indispensable for HCV infection. Using the JFH-1 fully infectious cell-culture competent virus in Huh 7 hepatoma cells with TALENmediated gene deletion of apoB(APOB KO), we found a significant reduction in HCV RNA and protein levels following infection. Pseudoparticle and replicon models demonstrated that apo B did not play a role in HCV entry or replication. However, the virus produced by APOB KO cells had significantly diminished infectivity as measured by the TCID-50 method compared to wildtype virus. Lipidomic analysis demonstrated that these virions have a fundamentally altered lipidome, with complete depletion of cholesterol esters. We further demonstrate that inhibition of apoB using mipomersen, an FDA-approved anti-sense oligonucleotide, results in a potent anti-HCV effect and significantly reduces the infectivity of the virus. CONCLUSION Apo B is required for the generation of fully infectious HCV virions, and inhibition of apo B with mipomersen blocks HCV. Targeting lipid metabolic pathways to impair viral infectivity represents a novel host targeted strategy to inhibit HCV.

关键词： Apolipoprotein Lipid Hepatitis C virus Gene silencing Viral replication

Design methods for antimicrobial peptides with improved performance

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Zoological Research 2023年第6期44卷 1095-1114页

作者： james Mwangi Peter Muiruri Kamau Rebecca Caroline Thuku Ren Lai Key Laboratory of Bioactive Peptides of Yunnan Province Engineering Laboratory of Peptides of Chinese Academy of SciencesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Centre for Non-Human PrimatesKunming Primate Research CentreNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Sino-African Joint Research CentreNew Cornerstone Science InstituteKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China Centre for Evolution and Conservation Biology Southern Marine Science and Engineering Guangdong LaboratoryGuangzhouGuangdong 511458China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more *** this regard,developing new antimicrobial agents to combat antibiotic-resistant strains has become a top *** peptides(AMPs),a ubiquitous class of naturally occurring compounds with broadspectrum antipathogenic activity,hold significant promise as an effective solution to the current antimicrobial resistance(AMR)*** AMPs have been identified and evaluated for their therapeutic application,with many already in the drug development *** distinct properties,such as high target specificity,potency,and ability to bypass microbial resistance mechanisms,make AMPs a promising alternative to traditional ***,several challenges,such as high toxicity,lability to proteolytic degradation,low stability,poor pharmacokinetics,and high production costs,continue to hamper their clinical ***,recent research has focused on optimizing the properties of AMPs to improve their *** understanding the physicochemical properties of AMPs that correspond to their activity,such as amphipathicity,hydrophobicity,structural conformation,amino acid distribution,and composition,researchers can design AMPs with desired and improved *** this review,we highlight some of the key strategies used to optimize the performance of AMPs,including rational design and de novo *** also discuss the growing role of predictive computational tools,utilizing artificial intelligence and machine learning,in the design and synthesis of highly efficacious lead drug candidates.

关键词： Antimicrobial resistance Antimicrobial peptides Design methods Peptidomimetics Artificial intelligence

Determination of the cellulase activity distribution in Clostridium thermocellum and Caldicellulosiruptor obsidiansis cultures using a fluorescent substrate

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Journal of Environmental Sciences 2015年第8期27卷 212-218页

作者： Jennifer L.Morrell-Falvey james G.Elkins Zhi-Wu Wang Bio Energy Science Center Biosciences Division Oak Ridge National Laboratory The Ohio State University ATI

This study took advantage of resorufin cellobioside as a fluorescent substrate to determine the distribution of cellulase activity in cellulosic biomass fermentation systems. Cellulolytic biofilms were found to express nearly four orders greater cellulase activity compared to planktonic cultures of Clostridium thermocellum and Caldicellulosiruptor obsidiansis, which can be primarily attributed to the high cell concentration and surface attachment. The formation of biofilms results in cellulases being secreted close to their substrates, which appears to be an energetically favorable stategy for insoluble substrate utilization. For the same reason,cellulases should be closely associated with the surfaces of suspended cell in soluble substrate-fed culture, which has been verified with cellobiose-fed cultures of C. thermocellum and C. obsidiansis. This study addressed the importance of cellulase activity distribution in cellulosic biomass fermentation, and provided theoretical foundation for the leading role of biofilm in cellulose degradation. System optimization and reactor designs that promote biofilm formation in cellulosic biomass hydrolysis may promise an improved cellulosic biofuel process.

关键词： Thermophilic Biofilm Cellulose Cellulase Biofuel

Orthopaedic tissue engineering and stem cells -an unfulfilled promise

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Biomaterials Translational 2021年第2期2卷 89-90页

作者： james T.Triffitt Botnar Research Centre Nuffield Department of OrthopaedicsRheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK

Despite being over thirty years since there was proof that the hypothetical osteogenic stem cell existed,1 demonstration of any dramatic value for the use of such cells in orthopaedic clinical practice by tissue engineering approaches has not yet been *** is notwithstanding extensive studies concerning the likely nature and potentials of these cells in countless in vitro and in vivo *** part,this is based on the confusion caused by exaggeration of claims by unreliable,or at best naïve,investigators and opportunistic entrepreneurs who have grossly misinterpreted data from many ill-conceived studies.2,3 This pseudo-science has been harmful,especially to the stem cell field,both academically and commercially.

关键词： likely concerning spite

Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia

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Neural Regeneration Research 2015年第9期10卷 1395-1396页

作者： Jenny A.K.Ekberg james A.St John Eskitis Institute for Drug Discovery Griffith University School of Biomedical Sciences Queensland University of Technology

OECs for spinal cord repair： Is repairing the iniured spinal cord by olfactory ensheathing cell （OEC） transplantation pos- sible？ A recent human trial in which a paralysed man regained some function after transplantation of partially purified OECs suggests that this therapy may be a successful approach （Ta- bakow et al., 2014）. In another human trial in which olfactory mucosa lamina propria was transplanted, patients recovered some motor and sensory function （Wang et al., 2015）. While these results show promise, it is clear that improvements are needed to provide patients with increased functional output. Strategies to improve the therapeutic use of OECs may include improving the purification of the OECs used for transplantation, using them in combination with growth factors to combat the inhibitory environment and improve anon growth, the use of nerve bridges, advanced physiotherapy and the use of exo- skeleton robotics to reinforce functional connections. Of all these approaches, it is probably is primarily addressed to ensure crucial that the purity of OECs consistency in outcomes.

关键词： cell Olfactory ensheathing cells for spinal cord repair crucial differences between subpopulations of the glia

Human recombinant soluble ACE2(hrsACE2)shows promise for treating severe COVID19

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Signal Transduction and Targeted Therapy 2020年第1期5卷 303-304页

作者： Tarek Mohamed Abd El-Aziz Ahmed Al-Sabi james D.Stockand Department of Cellular and Integrative Physiology University of Texas Health Science Center at San AntonioSan AntonioTX 78229-3900USA Zoology Department Faculty of ScienceMinia UniversityEl-Minia 61519Egypt College of Engineering and Technology American University of the Middle EastKuwaitKuwait

A recent study by Zoufaly et *** in The Lancet Respiratory Medicine describes encouraging data from the first severe COVID-19 patient successfully treated with human recombinant soluble angiotensin-converting enzyme-2(hrsACE2).1 The published data document upon treatment of an adaptive immune response,the disappearance of the virus swiftly from the serum,the nasal cavity and lungs,and a reduction of inflammatory cytokine levels that are critical for COVID-19 ***,the use of hrsACE2 did not impede the generation of neutralizing antibodies,leading to a significant clinical improvement of the treated patient.

关键词： ACE2 al cavity

Leading Approaches to Vascularize Kidney Constructs in Tissue Engineering

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Engineering 2022年第12期19卷 117-127页

作者： Diana S.Lim John D.Jackson Anthony Atala james J.Yoo Wake Forest Institute for Regenerative Medicine Wake Forest University School of MedicineMedical Center BoulevardNC 27157USA

There is an unprecedented need for new treatments for renal failure,as the incidence of this disease is increasing disproportionately to advancements in *** treatments are limited by the availability of viable organs,for which there is a worldwide *** treatment modalities also require a substantial amount of infrastructure,significantly limiting the access to care in most *** tissue engineering approaches promise to develop alternative solutions that address many of the inadequacies in current *** many advancements have been made—primarily in the past decade—in biofabrication and whole-organ tissue engineering,many challenges *** major hindrance to the progress of current tissue engineering approaches is establishing successful vascularization of developed engineered tissue *** review focuses on the recent advancements that address the vascular challenge,including the biofabrication of vasculature,whole-organ engineering through decellularization and recellularization approaches,microscale organogenesis,and vascularization using organoids in the context of kidney tissue *** also highlight the specific challenges that remain in developing successful strategies capable of clinical translation.

关键词： Kidney Vascularization Tissue engineering Biofabrication Organoids

Colorectal cancer risk in Crohn's disease

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World Journal of Gastroenterology 2008年第12期14卷 1810-1811页

作者： Hugh james Freeman Department of Medicine (Gastro-enterology) University of British Columbia UBC Hospital Vancouver BC Canada

There is recognized increased risk for colorectal cancer in patients with inflammatory bowel disease, particularly in long-standing and extensive ulcerative colitis. There also appears to be an increased rate of intestinal cancer in Crohn's disease, including both colon and small bowel sites. In Crohn's disease, evidence suggests that detection of colorectal cancer may be delayed with a worse progno-sis. Some risk factors for cancer in Crohn's disease include the extent of inflammatory change within the colon and the presence of bypassed or excluded segments, inclu-ding rectal "stump" cancer. In addition, the risk for other types of intestinal neoplasms may be increased in Crohn's disease, including lymphoma and carcinoid tumors. Earlier detection of colorectal cancer based on colonoscopy scre-ening and surveillance may be achieved but, to date, this has not translated into a positive survival benefit. Moreo-ver, newer staining methods and evolving micro-endos-copic techniques show promise, but have not significantly altered management. Future research should focus on development of molecular or other bio-markers that might predict future dysplasia or cancer development in Crohn's disease.

关键词： Colon cancer Crohn's disease Surveillance Small bowel cancer