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Jagst M, Gömer A, Augustyniak S, Klöhn M, Rehm A, Ulrich RG, Bader V, Winklhofer KF, Brüggemann Y, Gold R, Gisevius B, Todt D, Steinmann E. Modeling extrahepatic hepatitis E virus infection in induced human primary neurons. Proc Natl Acad Sci U S A 2024; 121:e2411434121. [PMID: 39546567 PMCID: PMC11588080 DOI: 10.1073/pnas.2411434121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 09/27/2024] [Indexed: 11/17/2024] Open
Abstract
Hepatitis E virus (HEV) infections are one of the most common causes of acute viral hepatitis, annually causing over 3 million symptomatic cases and 70,000 deaths worldwide. Historically, HEV was described as a hepatotropic virus, but has recently been associated with various extrahepatic manifestations including neurological disorders such as Guillain-Barré syndrome and neuralgic amyotrophy. However, the underlying pathogenesis of these neurological diseases remains largely unknown. The aim of this study was to investigate extrahepatic HEV manifestations in a neuronal model system using human-induced primary neurons (iPNs). Renal epithelial cells from human urine were reprogrammed to induced pluripotent stem cells to generate neuronal progenitor cells, which were subsequently differentiated into iPNs over 21 d. These iPNs supported HEV infection preferentially in neurite-bearing cells. Transcriptional profiling of the neuronal development process as well as viral infection dynamics in iPNs uncovered a lack of antiviral innate immune responses to HEV infection with only an intrinsic expression of distinct interferon-regulated genes and signaling molecules. Viral open reading frame 2 encoded capsid protein could be visualized by volumetric three-dimensional reconstitution within the neurites, which were reduced in length in an HEV inoculation-dependent manner. In conclusion, this neuron-derived human model system provides a powerful tool for studying extrahepatic manifestations of HEV infection. It further indicates a potential mechanism of pathogenesis driven by the interaction between host and viral factors.
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Affiliation(s)
- Michelle Jagst
- Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum44801, Germany
- Institute of Virology, University of Veterinary Medicine Hannover, Hannover30559, Germany
| | - André Gömer
- Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum44801, Germany
| | - Sanja Augustyniak
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum44801, Germany
| | - Mara Klöhn
- Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum44801, Germany
| | - Adriana Rehm
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum44801, Germany
| | - Rainer G. Ulrich
- Friedrich-Loeffler-Institut, Institute of Novel and Emerging Infectious Diseases, Greifswald-Insel Riems17493, Germany
- German Centre for Infection Research, Partner site Hamburg-Lübeck-Borstel-Riems, Greifswald-Insel Riems17493, Germany
| | - Verian Bader
- Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum44801, Germany
| | - Konstanze F. Winklhofer
- Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr University Bochum, Bochum44801, Germany
| | - Yannick Brüggemann
- Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum44801, Germany
| | - Ralf Gold
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum44801, Germany
| | - Barbara Gisevius
- Department of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum44801, Germany
| | - Daniel Todt
- Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum44801, Germany
- European Virus Bioinformatics Center, Jena07743, Germany
| | - Eike Steinmann
- Department for Molecular and Medical Virology, Institute for Hygiene and Microbiology, Ruhr University Bochum, Bochum44801, Germany
- German Centre for Infection Research (DZIF), External Partner Site, Bochum44801, Germany
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Mohite P, Puri A, Dave R, Budar A, Munde S, Ghosh SB, Alqahtani T, Shmrany HA, Kumer A, Dhara B. Unlocking the therapeutic potential: odyssey of induced pluripotent stem cells in precision cell therapies. Int J Surg 2024; 110:6432-6455. [PMID: 38963728 PMCID: PMC11487032 DOI: 10.1097/js9.0000000000001892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 06/17/2024] [Indexed: 07/06/2024]
Abstract
This review explores the application of induced pluripotent stem cells (iPSCs) in regenerative medicine. The therapeutic significance of iPSC-derived cell therapy within regenerative medicine, emphasizes their reprogramming process and crucial role in cellular differentiation while setting the purpose and scope for the comprehensive exploration of iPSC-derived cell therapy. The subsequent sections intricately examine iPSC-derived cell therapy, unraveling the diverse derivatives of iPSCs and striking a delicate balance between advantages and limitations in therapeutic applications. Mechanisms of action, revealing how iPSC-derived cells seamlessly integrate into tissues, induce regeneration, and contribute to disease modeling and drug screening advancements is discussed. The analysis extends to clinical trials, shedding light on outcomes, safety considerations, and ethical dimensions. Challenges and concerns, including the risk of tumorigenesis and scalability issues, are explored. The focus extends to disease-specific applications, showcasing iPSC-derived cell therapy as a promising avenue for various medical conditions, supported by illustrative case studies. Future directions and research needs are outlined, identifying areas for further exploration, safety considerations and potential enhancements that will shape the future landscape of iPSC-derived therapies. In conclusion, this review provides a significant understanding of iPSC-derived cell therapy's status that contemplates the implications for regenerative medicine and personalized treatment using iPSCs, offering a comprehensive perspective on the evolving field within the confines of a dynamic and promising scientific frontier.
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Affiliation(s)
- Popat Mohite
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra
| | - Abhijeet Puri
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra
| | - Roshan Dave
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra
| | - Aarati Budar
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra
| | - Shubham Munde
- AETs St. John Institute of Pharmacy and Research, Palghar, Maharashtra
| | - Shruti Bagchi Ghosh
- Department of Pharmaceutical Chemistry, Calcutta Institute of Pharmaceutical Technology and Allied Health Science, Uluberia, Howrah
| | - Taha Alqahtani
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha
| | - Humood Al Shmrany
- Department of Medical Laboratory Sciences, College of Applied medical sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Ajoy Kumer
- Department of Chemistry, IUBAT-International University of Business Agriculture & Technology, Dhaka, Bangladesh
| | - Bikram Dhara
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, India
- Department of Health Sciences, Novel Global Community and Educational Foundation. Hebersham, NSW, Australia
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3
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Haase S, Kuhbandner K, Mühleck F, Gisevius B, Freudenstein D, Hirschberg S, Lee DH, Kuerten S, Gold R, Haghikia A, Linker RA. Dietary galactose exacerbates autoimmune neuroinflammation via advanced glycation end product-mediated neurodegeneration. Front Immunol 2024; 15:1367819. [PMID: 39185426 PMCID: PMC11341352 DOI: 10.3389/fimmu.2024.1367819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 07/26/2024] [Indexed: 08/27/2024] Open
Abstract
Background Recent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose, galactose is a common sugar in the so-called Western diet. Methods We investigated the effect of a galactose-rich diet during neuroinflammation using myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE) as a model disease. We investigated peripheral immune reactions and inflammatory infiltration by ex vivo flow cytometry analysis and performed histological staining of the spinal cord to analyze effects of galactose in the central nervous system (CNS). We analyzed the formation of advanced glycation end products (AGEs) by fluorescence measurements and investigated galactose as well as galactose-induced AGEs in oligodendroglial cell cultures and induced pluripotent stem cell-derived primary neurons (iPNs). Results Young mice fed a galactose-rich diet displayed exacerbated disease symptoms in the acute phase of EAE as well as impaired recovery in the chronic phase. Galactose did not affect peripheral immune reactions or inflammatory infiltration into the CNS, but resulted in increased demyelination, oligodendrocyte loss and enhanced neuro-axonal damage. Ex vivo analysis revealed an increased apoptosis of oligodendrocytes isolated from mice adapted on a galactose-rich diet. In vitro, treatment of cells with galactose neither impaired the maturation nor survival of oligodendroglial cells or iPNs. However, incubation of proteins with galactose in vitro led to the formation AGEs, that were increased in the spinal cord of EAE-diseased mice fed a galactose-rich diet. In oligodendroglial and neuronal cultures, treatment with galactose-induced AGEs promoted enhanced cell death compared to control treatment. Conclusion These results imply that galactose-induced oligodendrocyte and myelin damage during neuroinflammation may be mediated by AGEs, thereby identifying galactose and its reactive products as potential dietary risk factors for neuroinflammatory diseases such as MS.
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MESH Headings
- Animals
- Galactose/administration & dosage
- Encephalomyelitis, Autoimmune, Experimental/immunology
- Encephalomyelitis, Autoimmune, Experimental/pathology
- Encephalomyelitis, Autoimmune, Experimental/metabolism
- Mice
- Glycation End Products, Advanced/metabolism
- Glycation End Products, Advanced/administration & dosage
- Neuroinflammatory Diseases/immunology
- Neuroinflammatory Diseases/pathology
- Neuroinflammatory Diseases/metabolism
- Neuroinflammatory Diseases/etiology
- Mice, Inbred C57BL
- Female
- Oligodendroglia/metabolism
- Oligodendroglia/pathology
- Oligodendroglia/immunology
- Disease Models, Animal
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Affiliation(s)
- Stefanie Haase
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Kristina Kuhbandner
- Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
| | - Florian Mühleck
- Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
| | - Barbara Gisevius
- Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany
| | - David Freudenstein
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Sarah Hirschberg
- Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany
| | - De-Hyung Lee
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
| | - Stefanie Kuerten
- Institute of Neuroanatomy, Faculty of Medicine, University of Bonn and University Hospital Bonn, Bonn, Germany
| | - Ralf Gold
- Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Aiden Haghikia
- Department of Neurology, University Medicine Magdeburg, Magdeburg, Germany
| | - Ralf A. Linker
- Department of Neurology, University Hospital Regensburg, Regensburg, Germany
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Gisevius B, Duscha A, Poschmann G, Stühler K, Motte J, Fisse AL, Augustyniak S, Rehm A, Renk P, Böse C, Hubert D, Peters K, Jagst M, Gömer A, Todt D, Bader V, Tokic M, Hirschberg S, Krogias C, Trampe N, Coutourier C, Winnesberg C, Steinmann E, Winklhofer K, Gold R, Haghikia A. Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons. Brain Commun 2024; 6:fcae182. [PMID: 38894951 PMCID: PMC11184351 DOI: 10.1093/braincomms/fcae182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 03/21/2024] [Accepted: 05/31/2024] [Indexed: 06/21/2024] Open
Abstract
Neurodegeneration in the autoimmune disease multiple sclerosis still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with multiple sclerosis, supplementation of the short-chain fatty acid propionic acid, as a microbial metabolite derived from the fermentation of a high-fiber diet, has previously been shown to regulate inflammation accompanied by neuroprotective properties. We set out to determine whether the neuroprotective impact of propionic acid is a direct mode of action of short-chain fatty acids on CNS neurons. We analysed neurite recovery in the presence of the short-chain fatty acid propionic acid and butyric acid in a reverse-translational disease-in-a-dish model of human-induced primary neurons differentiated from people with multiple sclerosis-derived induced pluripotent stem cells. We found that recovery of damaged neurites is induced by propionic acid and butyric acid. We could also show that administration of butyric acid is able to enhance propionic acid-associated neurite recovery. Whole-cell proteome analysis of induced primary neurons following recovery in the presence of propionic acid revealed abundant changes of protein groups that are associated with the chromatin assembly, translational, and metabolic processes. We further present evidence that these alterations in the chromatin assembly were associated with inhibition of histone deacetylase class I/II following both propionic acid and butyric acid treatment, mediated by free fatty acid receptor signalling. While neurite recovery in the presence of propionic acid is promoted by activation of the anti-oxidative response, administration of butyric acid increases neuronal ATP synthesis in people with multiple sclerosis-specific induced primary neurons.
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Affiliation(s)
- Barbara Gisevius
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Alexander Duscha
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
- Department of Neurology, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Gereon Poschmann
- Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
- Molecular Proteomics Laboratory, BMFZ, Heinrich Heine University Düsseldorf, 40335 Düsseldorf, Germany
| | - Kai Stühler
- Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
- Molecular Proteomics Laboratory, BMFZ, Heinrich Heine University Düsseldorf, 40335 Düsseldorf, Germany
| | - Jeremias Motte
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Anna Lena Fisse
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Sanja Augustyniak
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Adriana Rehm
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Pia Renk
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Celina Böse
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Diana Hubert
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Kathrin Peters
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Michelle Jagst
- Department for Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany
- Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
| | - André Gömer
- Department for Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany
| | - Daniel Todt
- Department for Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany
- European Virus Bioinformatics Center (EVBC), 07743 Jena, Germany
| | - Verian Bader
- Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr-University Bochum, 44801 Bochum, Germany
| | - Marianne Tokic
- Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, 44780 Bochum, Germany
| | - Sarah Hirschberg
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Christos Krogias
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Nadine Trampe
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Charlotta Coutourier
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Carmen Winnesberg
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Eike Steinmann
- Department for Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany
| | - Konstanze Winklhofer
- Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr-University Bochum, 44801 Bochum, Germany
- Cluster of Excellence RESOLV, 44801 Bochum, Germany
| | - Ralf Gold
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
| | - Aiden Haghikia
- Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
- Department of Neurology, Otto-von-Guericke University, 39120 Magdeburg, Germany
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Ren R, Jiang J, Li X, Zhang G. Research progress of autoimmune diseases based on induced pluripotent stem cells. Front Immunol 2024; 15:1349138. [PMID: 38720903 PMCID: PMC11076788 DOI: 10.3389/fimmu.2024.1349138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 04/12/2024] [Indexed: 05/12/2024] Open
Abstract
Autoimmune diseases can damage specific or multiple organs and tissues, influence the quality of life, and even cause disability and death. A 'disease in a dish' can be developed based on patients-derived induced pluripotent stem cells (iPSCs) and iPSCs-derived disease-relevant cell types to provide a platform for pathogenesis research, phenotypical assays, cell therapy, and drug discovery. With rapid progress in molecular biology research methods including genome-sequencing technology, epigenetic analysis, '-omics' analysis and organoid technology, large amount of data represents an opportunity to help in gaining an in-depth understanding of pathological mechanisms and developing novel therapeutic strategies for these diseases. This paper aimed to review the iPSCs-based research on phenotype confirmation, mechanism exploration, drug discovery, and cell therapy for autoimmune diseases, especially multiple sclerosis, inflammatory bowel disease, and type 1 diabetes using iPSCs and iPSCs-derived cells.
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Affiliation(s)
| | | | | | - Guirong Zhang
- Shandong Yinfeng Academy of Life Science, Jinan, Shandong, China
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Daviaud N, Chen E, Edwards T, Sadiq SA. Cerebral organoids in primary progressive multiple sclerosis reveal stem cell and oligodendrocyte differentiation defect. Biol Open 2023; 12:286917. [PMID: 36744877 PMCID: PMC10040243 DOI: 10.1242/bio.059845] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 01/30/2023] [Indexed: 02/07/2023] Open
Abstract
Multiple sclerosis (MS) is an auto-immune inflammatory disorder affecting the central nervous system. The cause of the disease is unknown but both genetic and environmental factors are implicated in the pathogenesis. We derived cerebral organoids from induced pluripotent stem cells (iPSC) of healthy control subjects as well as from primary progressive MS (PPMS), secondary progressive MS (SPMS) and relapsing remitting MS (RRMS) patients to better understand the pathologic basis of the varied clinical phenotypic expressions of MS. In MS organoids, most notably in PPMS, we observed a decrease of proliferation marker Ki67 and a reduction of the SOX2+ stem cell pool associated with an increased expression of neuronal markers CTIP2 and TBR1 as well as a strong decrease of oligodendrocyte differentiation. This dysregulation of the stem cell pool is associated with a decreased expression of the cell cycle inhibitor p21. Our findings show that the genetic background of a patient can directly alter stem cell function, provides new insights on the innate cellular dysregulation in MS and identifies p21 pathway as a new potential target for therapeutic strategies in MS.
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Affiliation(s)
- Nicolas Daviaud
- Tisch Multiple Sclerosis Research Center of New York, 521 W. 57th St., 4th floor, New York, NY 10019, USA
| | - Eric Chen
- Tisch Multiple Sclerosis Research Center of New York, 521 W. 57th St., 4th floor, New York, NY 10019, USA
| | - Tara Edwards
- Tisch Multiple Sclerosis Research Center of New York, 521 W. 57th St., 4th floor, New York, NY 10019, USA
| | - Saud A Sadiq
- Tisch Multiple Sclerosis Research Center of New York, 521 W. 57th St., 4th floor, New York, NY 10019, USA
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7
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Fortune AJ, Fletcher JL, Blackburn NB, Young KM. Using MS induced pluripotent stem cells to investigate MS aetiology. Mult Scler Relat Disord 2022; 63:103839. [DOI: 10.1016/j.msard.2022.103839] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 04/01/2022] [Accepted: 04/29/2022] [Indexed: 12/15/2022]
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8
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Recchia K, Machado LS, Botigelli RC, Pieri NCG, Barbosa G, de Castro RVG, Marques MG, Pessôa LVDF, Fantinato Neto P, Meirelles FV, Souza AFD, Martins SMMK, Bressan FF. In vitro induced pluripotency from urine-derived cells in porcine. World J Stem Cells 2022; 14:231-244. [PMID: 35432738 PMCID: PMC8968213 DOI: 10.4252/wjsc.v14.i3.231] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/11/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The generation of induced pluripotent stem cells (iPSC) has been a game-changer in translational and regenerative medicine; however, their large-scale applicability is still hampered by the scarcity of accessible, safe, and reproducible protocols. The porcine model is a large biomedical model that enables translational applications, including gene editing, long term in vivo and offspring analysis; therefore, suitable for both medicine and animal production.
AIM To reprogramme in vitro into pluripotency, and herein urine-derived cells (UDCs) were isolated from porcine urine.
METHODS The UDCs were reprogrammed in vitro using human or murine octamer-binding transcription factor 4 (OCT4), SRY-box2 (SOX2), Kruppel-like factor 4 (KLF4), and C-MYC, and cultured with basic fibroblast growth factor (bFGF) supplementation. To characterize the putative porcine iPSCs three clonal lineages were submitted to immunocytochemistry for alkaline phosphatase (AP), OCT4, SOX2, NANOG, TRA1 81 and SSEA 1 detection. Endogenous transcripts related to the pluripotency (OCT4, SOX2 and NANOG) were analyzed via reverse transcription quantitative real-time polymerase chain reaction in different time points during the culture, and all three lineages formed embryoid bodies (EBs) when cultured in suspension without bFGF supplementation.
RESULTS The UDCs were isolated from swine urine samples and when at passage 2 submitted to in vitro reprogramming. Colonies of putative iPSCs were obtained only from UDCs transduced with the murine factors (mOSKM), but not from human factors (hOSKM). Three clonal lineages were isolated and further cultured for at least 28 passages, all the lineages were positive for AP detection, the OCT4, SOX2, NANOG markers, albeit the immunocytochemical analysis also revealed heterogeneous phenotypic profiles among lineages and passages for NANOG and SSEA1, similar results were observed in the abundance of the endogenous transcripts related to pluripotent state. All the clonal lineages when cultured in suspension without bFGF were able to form EBs expressing ectoderm and mesoderm layers transcripts.
CONCLUSION For the first time UDCs were isolated in the swine model and reprogrammed into a pluripotent-like state, enabling new numerous applications in both human or veterinary regenerative medicine.
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Affiliation(s)
- Kaiana Recchia
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Lucas Simões Machado
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Ramon Cesar Botigelli
- Department of Pharmacology and Biotechnology, Institute of Bioscience, São Paulo State University, Botucatu 18618-689, São Paulo, Brazil
| | - Naira Caroline Godoy Pieri
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Gabriela Barbosa
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | | | - Mariana Groke Marques
- Embrapa Suínos e Aves, Empresa Brasileira de Pesquisa Agropecuária, Concordia 89715-899, Santa Catarina, Brazil
| | - Laís Vicari de Figueiredo Pessôa
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Paulo Fantinato Neto
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Flávio Vieira Meirelles
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Aline Fernanda de Souza
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | | | - Fabiana Fernandes Bressan
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
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9
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Cerrizuela S, Vega-Lopez GA, Méndez-Maldonado K, Velasco I, Aybar MJ. The crucial role of model systems in understanding the complexity of cell signaling in human neurocristopathies. WIREs Mech Dis 2022; 14:e1537. [PMID: 35023327 DOI: 10.1002/wsbm.1537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 08/26/2021] [Accepted: 08/30/2021] [Indexed: 11/07/2022]
Abstract
Animal models are useful to study the molecular, cellular, and morphogenetic mechanisms underlying normal and pathological development. Cell-based study models have emerged as an alternative approach to study many aspects of human embryonic development and disease. The neural crest (NC) is a transient, multipotent, and migratory embryonic cell population that generates a diverse group of cell types that arises during vertebrate development. The abnormal formation or development of the NC results in neurocristopathies (NCPs), which are characterized by a broad spectrum of functional and morphological alterations. The impaired molecular mechanisms that give rise to these multiphenotypic diseases are not entirely clear yet. This fact, added to the high incidence of these disorders in the newborn population, has led to the development of systematic approaches for their understanding. In this article, we have systematically reviewed the ways in which experimentation with different animal and cell model systems has improved our knowledge of NCPs, and how these advances might contribute to the development of better diagnostic and therapeutic tools for the treatment of these pathologies. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Congenital Diseases > Stem Cells and Development Congenital Diseases > Molecular and Cellular Physiology Neurological Diseases > Genetics/Genomics/Epigenetics.
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Affiliation(s)
- Santiago Cerrizuela
- Division of Molecular Neurobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.,Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Tucumán, Argentina
| | - Guillermo A Vega-Lopez
- Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Tucumán, Argentina.,Instituto de Biología "Dr. Francisco D. Barbieri", Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina
| | - Karla Méndez-Maldonado
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.,Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Iván Velasco
- Instituto de Fisiología Celular - Neurociencias, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.,Laboratorio de Reprogramación Celular del Instituto de Fisiología Celular, UNAM en el Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suárez", Ciudad de México, Mexico
| | - Manuel J Aybar
- Instituto Superior de Investigaciones Biológicas (INSIBIO, CONICET-UNT), Tucumán, Argentina.,Instituto de Biología "Dr. Francisco D. Barbieri", Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, Tucumán, Argentina
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10
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Ray A, Joshi JM, Sundaravadivelu PK, Raina K, Lenka N, Kaveeshwar V, Thummer RP. An Overview on Promising Somatic Cell Sources Utilized for the Efficient Generation of Induced Pluripotent Stem Cells. Stem Cell Rev Rep 2021; 17:1954-1974. [PMID: 34100193 DOI: 10.1007/s12015-021-10200-3] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2021] [Indexed: 01/19/2023]
Abstract
Human induced Pluripotent Stem Cells (iPSCs) have enormous potential in understanding developmental biology, disease modeling, drug discovery, and regenerative medicine. The initial human iPSC studies used fibroblasts as a starting cell source to reprogram them; however, it has been identified to be a less appealing somatic cell source by numerous studies due to various reasons. One of the important criteria to achieve efficient reprogramming is determining an appropriate starting somatic cell type to induce pluripotency since the cellular source has a major influence on the reprogramming efficiency, kinetics, and quality of iPSCs. Therefore, numerous groups have explored various somatic cell sources to identify the promising sources for reprogramming into iPSCs with different reprogramming factor combinations. This review provides an overview of promising easily accessible somatic cell sources isolated in non-invasive or minimally invasive manner such as keratinocytes, urine cells, and peripheral blood mononuclear cells used for the generation of human iPSCs derived from healthy and diseased subjects. Notably, iPSCs generated from one of these cell types derived from the patient will offer ethical and clinical advantages. In addition, these promising somatic cell sources have the potential to efficiently generate bona fide iPSCs with improved reprogramming efficiency and faster kinetics. This knowledge will help in establishing strategies for safe and efficient reprogramming and the generation of patient-specific iPSCs from these cell types.
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Affiliation(s)
- Arnab Ray
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India
| | - Jahnavy Madhukar Joshi
- Central Research Laboratory, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, 580009, Karnataka, India
| | - Pradeep Kumar Sundaravadivelu
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India
| | - Khyati Raina
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India
| | - Nibedita Lenka
- National Centre for Cell Science, S. P. Pune University Campus, Pune - 411007, Ganeshkhind, Maharashtra, India
| | - Vishwas Kaveeshwar
- Central Research Laboratory, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara University, Dharwad, 580009, Karnataka, India.
| | - Rajkumar P Thummer
- Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, 781039, Assam, India.
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11
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Li H, Lian G, Wang G, Yin Q, Su Z. A review of possible therapies for multiple sclerosis. Mol Cell Biochem 2021; 476:3261-3270. [PMID: 33886059 DOI: 10.1007/s11010-021-04119-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 02/23/2021] [Indexed: 01/22/2023]
Abstract
Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system with a wide range of symptoms, like executive function defect, cognitive dysfunction, blurred vision, decreased sensation, spasticity, fatigue, and other symptoms. This neurological disease is characterized by the destruction of the blood-brain barrier, loss of myelin, and damage to neurons. It is the result of immune cells crossing the blood-brain barrier into the central nervous system and attacking self-antigens. Heretofore, many treatments proved that they can retard the progression of the disease even though there is no cure. Therefore, treatments aimed at improving patients' quality of life and reducing adverse drug reactions and costs are essential. In this review, the treatment approaches to alleviate the progress of MS include the following: pharmacotherapy, antibody therapy, cell therapy, gene therapy, and surgery. The current treatment methods of MS are described in terms of the prevention of myelin shedding, the promotion of myelin regeneration, and the protection of neurons.
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Affiliation(s)
- Hui Li
- Hengyang Medical School, University of South China, Hengyang City, 421001, Hunan Province, China
| | - Gaojian Lian
- Hengyang Medical School, University of South China, Hengyang City, 421001, Hunan Province, China
| | - Guang Wang
- Hengyang Medical School, University of South China, Hengyang City, 421001, Hunan Province, China
| | - Qianmei Yin
- Hengyang Medical School, University of South China, Hengyang City, 421001, Hunan Province, China
| | - Zehong Su
- Hengyang Medical School, University of South China, Hengyang City, 421001, Hunan Province, China.
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12
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Mutukula N, Man Z, Takahashi Y, Iniesta Martinez F, Morales M, Carreon-Guarnizo E, Hernandez Clares R, Garcia-Bernal D, Martinez Martinez L, Lajara J, Nuñez Delicado E, Meca Lallana JE, Izpisua Belmonte JC. Generation of RRMS and PPMS specific iPSCs as a platform for modeling Multiple Sclerosis. Stem Cell Res 2021; 53:102319. [PMID: 33894548 DOI: 10.1016/j.scr.2021.102319] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 03/05/2021] [Accepted: 03/26/2021] [Indexed: 11/25/2022] Open
Abstract
The advent of cellular reprogramming technology converting somatic cells into induced pluripotent stem cells (iPSCs) has revolutionized our understandings of neurodegenerative diseases that are otherwise hard to access and model. Multiple Sclerosis (MS) is a chronic demyelinating, inflammatory disease of central nervous system eventually causing neuronal death and accompanied disabilities. Here, we report the generation of several relapsing-remitting MS (RRMS) and primary progressive MS (PPMS) iPSC lines from MS patients along with their age matched healthy controls from peripheral blood mononuclear cells (PBMC). These patient specific iPSC lines displayed characteristic embryonic stem cell (ESC) morphology and exhibited pluripotency marker expression. Moreover, these MS iPSC lines were successfully differentiated into neural progenitor cells (NPC) after subjecting to neural induction. Furthermore, we identified the elevated expression of cellular senescence hallmarks in RRMS and PPMS neural progenitors unveiling a novel drug target avenue of MS pathophysiology. Thus, our study altogether offers both RRMS and PPMS iPSC cellular models as a good tool for better understanding of MS pathologies and drug testing.
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Affiliation(s)
- Naresh Mutukula
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
| | - Zhiqiu Man
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
| | - Yuta Takahashi
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
| | - Francisca Iniesta Martinez
- Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR, Department of Neurology. "Virgen de la Arrixaca" Clinical University Hospital, IMIB-Arrixaca, Murcia, Spain; Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain
| | - Mariana Morales
- Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
| | - Ester Carreon-Guarnizo
- Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR, Department of Neurology. "Virgen de la Arrixaca" Clinical University Hospital, IMIB-Arrixaca, Murcia, Spain; Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain
| | - Rocio Hernandez Clares
- Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR, Department of Neurology. "Virgen de la Arrixaca" Clinical University Hospital, IMIB-Arrixaca, Murcia, Spain; Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain
| | - David Garcia-Bernal
- Hematopoietic Transplant and Cellular Therapy Unit, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, Medicine Department, University of Murcia, Murcia, Spain
| | | | - Jeronimo Lajara
- Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain
| | | | - Jose E Meca Lallana
- Clinical Neuroimmunology Unit and Multiple Sclerosis CSUR, Department of Neurology. "Virgen de la Arrixaca" Clinical University Hospital, IMIB-Arrixaca, Murcia, Spain; Universidad Católica San Antonio de Murcia (UCAM), Murcia, Spain.
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13
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Generation of infant- and pediatric-derived urinary induced pluripotent stem cells competent to form kidney organoids. Pediatr Res 2020; 87:647-655. [PMID: 31629364 DOI: 10.1038/s41390-019-0618-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 09/23/2019] [Accepted: 10/01/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Human induced pluripotent stem cells (iPSCs) are a promising tool to investigate pathogenic mechanisms underlying human genetic conditions, such as congenital anomalies of the kidney and urinary tract (CAKUT). Currently, iPSC-based research in pediatrics is limited by the invasiveness of cell collection. METHODS Urine cells (UCs) were isolated from pediatric urine specimens, including bag collections, and reprogrammed using episomal vectors into urinary iPSCs (UiPSCs). Following iPSC-quality assessment, human kidney organoids were generated. RESULTS UCs were isolated from 71% (12/17) of single, remnant urine samples obtained in an outpatient setting (patients 1 month-17 years, volumes 10-75 ml). Three independent UCs were reprogrammed to UiPSCs with early episome loss, confirmed pluripotency and normal karyotyping. Subsequently, these UiPSCs were successfully differentiated into kidney organoids, closely resembling organoids generated from control fibroblast-derived iPSCs. Importantly, under research conditions with immediate sample processing, UC isolation was successful 100% for target pediatric CAKUT patients and controls (11/11) after at most two urine collections. CONCLUSIONS Urine in small volumes or collected in bags is a reliable source for reprogrammable somatic cells that can be utilized to generate kidney organoids. This constitutes an attractive approach for patient-specific iPSC research involving infants and children with wide applicability and a low threshold for participation.
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14
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Autologous Hematopoietic Cell Transplantation in Multiple Sclerosis: Changing Paradigms in the Era of Novel Agents. Stem Cells Int 2019; 2019:5840286. [PMID: 31341484 PMCID: PMC6612973 DOI: 10.1155/2019/5840286] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 04/22/2019] [Accepted: 06/13/2019] [Indexed: 12/29/2022] Open
Abstract
Autologous hematopoietic stem cell transplantation (AHSCT) is established as a standard of care for diseases ranging from hematological malignancies to other neoplastic pathologies and severe immunological deficiencies. In April 1995, our group performed the first AHSCT in progressive multiple sclerosis (MS). Since then, a plethora of studies have been published with encouraging but controversial results. Major challenges in the field include appropriate patient selection, improvements in AHSCT procedure, and timing of this treatment modality. Beyond AHSCT, several new intravenous or oral agents have been developed and approved over the last 20 years in MS. The emergence of multiple effective therapies for MS has created a challenging scenario for both treating physicians and patients. Novel cell-based therapies other than AHSCT are also currently investigated in MS patients with promising results. Our review is aimed at summarizing state-of-the-art knowledge on basic principles and results of AHSCT in MS and its role compared to novel agents.
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15
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Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer's Disease. BIOMED RESEARCH INTERNATIONAL 2018; 2018:1483791. [PMID: 30112360 PMCID: PMC6077677 DOI: 10.1155/2018/1483791] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 06/19/2018] [Indexed: 12/16/2022]
Abstract
Alzheimer's disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.
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16
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Massa MG, David C, Jörg S, Berg J, Gisevius B, Hirschberg S, Linker RA, Gold R, Haghikia A. Testosterone Differentially Affects T Cells and Neurons in Murine and Human Models of Neuroinflammation and Neurodegeneration. THE AMERICAN JOURNAL OF PATHOLOGY 2017. [PMID: 28634006 DOI: 10.1016/j.ajpath.2017.03.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis. Although s.c. treatment with testosterone and aromatase inhibitor applied beginning on the day of immunization ameliorated initial course of disease, similar treatment administered therapeutically exacerbated chronic disease course. Spinal cord analyses of axonal densities reflected the clinical scores of the chronic phase. In vitro, testosterone treatment not only decreased Th1 and Th17 differentiation in an aromatase-independent fashion, but also exacerbated cell death in induced pluripotent stem cell-derived primary human neurons under oxidative stress conditions in an aromatase inhibitor-dependent manner. Thus, through the alleviation of inflammatory processes and the exacerbation of neurodegenerative processes, androgens may contribute to the epidemiologic sex differentials observed in MS prevalence and course.
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Affiliation(s)
- Megan G Massa
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany
| | - Christina David
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany
| | - Stefanie Jörg
- Department of Neurology, Friedrich-Alexander University-Erlangen-Nuremberg, Erlangen, Germany
| | - Johannes Berg
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany
| | - Barbara Gisevius
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany
| | - Sarah Hirschberg
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany
| | - Ralf A Linker
- Department of Neurology, Friedrich-Alexander University-Erlangen-Nuremberg, Erlangen, Germany
| | - Ralf Gold
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany
| | - Aiden Haghikia
- Department of Neurology, Ruhr University-Bochum, Bochum, Germany.
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Gurwitz D. Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders. DIALOGUES IN CLINICAL NEUROSCIENCE 2017. [PMID: 27757061 PMCID: PMC5067144 DOI: 10.31887/dcns.2016.18.3/dgurwitz] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.
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Affiliation(s)
- David Gurwitz
- Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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