Applying hydrodynamic pressure to efficiently generate induced pluripotent stem cells via reprogramming of centenarian skin fibroblasts
Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elder...
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| Veröffentlicht in: | PloS one Jg. 14; H. 4; S. e0215490 |
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| Sprache: | Englisch |
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Public Library of Science
25.04.2019
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| Abstract | Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105-107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. In conclusion, dermal fibroblasts from human subjects older than 100 years can be efficiently and reproducibly reprogrammed to fully pluripotent cells with minor modifications to the standard reprogramming procedures. Efficient generation of iPSCs from the elderly may provide a source of cells for the regeneration of tissues and organs with autologous cells as well as cellular models for the study of aging, longevity and age-related diseases. |
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| AbstractList | Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105-107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. In conclusion, dermal fibroblasts from human subjects older than 100 years can be efficiently and reproducibly reprogrammed to fully pluripotent cells with minor modifications to the standard reprogramming procedures. Efficient generation of iPSCs from the elderly may provide a source of cells for the regeneration of tissues and organs with autologous cells as well as cellular models for the study of aging, longevity and age-related diseases. Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105–107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. In conclusion, dermal fibroblasts from human subjects older than 100 years can be efficiently and reproducibly reprogrammed to fully pluripotent cells with minor modifications to the standard reprogramming procedures. Efficient generation of iPSCs from the elderly may provide a source of cells for the regeneration of tissues and organs with autologous cells as well as cellular models for the study of aging, longevity and age-related diseases. Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105-107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105-107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. In conclusion, dermal fibroblasts from human subjects older than 100 years can be efficiently and reproducibly reprogrammed to fully pluripotent cells with minor modifications to the standard reprogramming procedures. Efficient generation of iPSCs from the elderly may provide a source of cells for the regeneration of tissues and organs with autologous cells as well as cellular models for the study of aging, longevity and age-related diseases.Induced pluripotent stem cell (iPSC)-technology is an important platform in medicine and disease modeling. Physiological degeneration and disease onset are common occurrences in the aging population. iPSCs could offer regenerative medical options for age-related degeneration and disease in the elderly. However, reprogramming somatic cells from the elderly is inefficient when successful at all. Perhaps due to their low rates of replication in culture, traditional transduction and reprogramming approaches with centenarian fibroblasts met with little success. A simple and reproducible reprogramming process is reported here which enhances interactions of the cells with the viral vectors that leads to improved iPSC generation. The improved methods efficiently generates fully reprogrammed iPSC lines from 105-107 years old subjects in feeder-free conditions using an episomal, Sendai-Virus (SeV) reprogramming vector expressing four reprogramming factors. In conclusion, dermal fibroblasts from human subjects older than 100 years can be efficiently and reproducibly reprogrammed to fully pluripotent cells with minor modifications to the standard reprogramming procedures. Efficient generation of iPSCs from the elderly may provide a source of cells for the regeneration of tissues and organs with autologous cells as well as cellular models for the study of aging, longevity and age-related diseases. |
| Audience | Academic |
| Author | Franceschi, Claudio Zabulica, Mihaela Piccand, Julie Ravaioli, Francesco Kannisto, Kristina Capri, Miriam Garagnani, Paolo Gramignoli, Roberto Strom, Stephen C. Kraus, Marine R.-C. Vosough, Massoud |
| AuthorAffiliation | 2 University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Bologna, Italy 5 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden 8 Nestlé Institute of Health Sciences, Stem Cells, Lausanne, Switzerland 6 CNR, Institute of Molecular Genetics, IGM, Unit. Bologna, Bologna, Italy 4 CIG, Interdepartmental Center ‘L. Galvani’, Alma Mater Studiorum, Bologna, Italy 7 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy University of Minnesota Medical Center, UNITED STATES 3 Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden 1 Department of Stem Cells and Developmental Biology, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran |
| AuthorAffiliation_xml | – name: 4 CIG, Interdepartmental Center ‘L. Galvani’, Alma Mater Studiorum, Bologna, Italy – name: University of Minnesota Medical Center, UNITED STATES – name: 8 Nestlé Institute of Health Sciences, Stem Cells, Lausanne, Switzerland – name: 6 CNR, Institute of Molecular Genetics, IGM, Unit. Bologna, Bologna, Italy – name: 2 University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine, Bologna, Italy – name: 1 Department of Stem Cells and Developmental Biology, Cell Science Research Centre, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran – name: 5 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden – name: 3 Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden – name: 7 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy |
| Author_xml | – sequence: 1 givenname: Massoud surname: Vosough fullname: Vosough, Massoud – sequence: 2 givenname: Francesco orcidid: 0000-0001-6976-8489 surname: Ravaioli fullname: Ravaioli, Francesco – sequence: 3 givenname: Mihaela surname: Zabulica fullname: Zabulica, Mihaela – sequence: 4 givenname: Miriam surname: Capri fullname: Capri, Miriam – sequence: 5 givenname: Paolo surname: Garagnani fullname: Garagnani, Paolo – sequence: 6 givenname: Claudio surname: Franceschi fullname: Franceschi, Claudio – sequence: 7 givenname: Julie orcidid: 0000-0002-0719-8721 surname: Piccand fullname: Piccand, Julie – sequence: 8 givenname: Marine R.-C. orcidid: 0000-0002-9782-0472 surname: Kraus fullname: Kraus, Marine R.-C. – sequence: 9 givenname: Kristina surname: Kannisto fullname: Kannisto, Kristina – sequence: 10 givenname: Roberto surname: Gramignoli fullname: Gramignoli, Roberto – sequence: 11 givenname: Stephen C. surname: Strom fullname: Strom, Stephen C. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31022207$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:140896581$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| Copyright | COPYRIGHT 2019 Public Library of Science 2019 Vosough et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2019 Vosough et al 2019 Vosough et al |
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| DOI | 10.1371/journal.pone.0215490 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: All authors declare no competing interest relevant to the submitted research. Research funding was provided entirely by EU FP7 grant HUMAN (Health and the Understanding of Metabolism, Aging and Nutrition)(grant agreement: 602757) and Vetenskaprådet (Swedish Research Council) and the Törsten and Ragnar Söderberg stiftelsen as indicated in the Amended Funding Statement. Nestlé SA does not hold any patent, product in development, or marketed product related to the research described in the manuscript. Nestlé Institute of Health Science (Nestlé S.A) employed authors Julie Piccand and Marie R. C. Kraus at the time of manuscript submission. Nestlé SA did not provide economical support for study design, data collection and analysis. JP and MK contributions are articulated in the “author contribution” section. Involvement of Nestlé SA in the research does not alter adherence to PLOS ONE policies on sharing data and methods. |
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| Title | Applying hydrodynamic pressure to efficiently generate induced pluripotent stem cells via reprogramming of centenarian skin fibroblasts |
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