Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector
Abstract Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bo...
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| Veröffentlicht in: | Biomaterials 2013-07, Vol.34 (21), p.5336-5343 |
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| creator | Khan, Majad Narayanan, Karthikeyan Lu, Hongfang Choo, Yang Du, Chan Wiradharma, Nikken Yang, Yi-Yan Wan, Andrew C.A |
| description | Abstract Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3 h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation. |
| doi_str_mv | 10.1016/j.biomaterials.2013.03.072 |
| format | Article |
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We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3 h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2013.03.072</identifier><identifier>PMID: 23601660</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Animals ; Biological Assay ; Cationic ; Cationic bolaamphiphile ; Cations ; Cattle ; Cell Differentiation - drug effects ; Cell Lineage - drug effects ; Cell Nucleus - drug effects ; Cell Nucleus - metabolism ; Cell Proliferation - drug effects ; Cellular Reprogramming - drug effects ; Colony-Forming Units Assay ; Delivery systems ; Dentistry ; Fibroblasts ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Flow Cytometry ; Furans - chemistry ; Furans - pharmacology ; Genetic Vectors ; Humans ; Induced pluripotent stem cells ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Intracellular delivery ; Mathematical analysis ; Mice ; Mice, SCID ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Protein transduction ; Proteins ; Pyridones - chemistry ; Pyridones - pharmacology ; Recombinant Proteins - metabolism ; Reprogramming of fibroblasts ; Serum Albumin, Bovine - metabolism ; Stem cells ; Toxicity ; Transfection ; Vectors (mathematics)</subject><ispartof>Biomaterials, 2013-07, Vol.34 (21), p.5336-5343</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-5eb4a922b257da549947108a93af8dba9f1ded8f0911a8f98465ef5674253d43</citedby><cites>FETCH-LOGICAL-c501t-5eb4a922b257da549947108a93af8dba9f1ded8f0911a8f98465ef5674253d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961213003943$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23601660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Majad</creatorcontrib><creatorcontrib>Narayanan, Karthikeyan</creatorcontrib><creatorcontrib>Lu, Hongfang</creatorcontrib><creatorcontrib>Choo, Yang</creatorcontrib><creatorcontrib>Du, Chan</creatorcontrib><creatorcontrib>Wiradharma, Nikken</creatorcontrib><creatorcontrib>Yang, Yi-Yan</creatorcontrib><creatorcontrib>Wan, Andrew C.A</creatorcontrib><title>Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3 h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation.</description><subject>Advanced Basic Science</subject><subject>Animals</subject><subject>Biological Assay</subject><subject>Cationic</subject><subject>Cationic bolaamphiphile</subject><subject>Cations</subject><subject>Cattle</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Lineage - drug effects</subject><subject>Cell Nucleus - drug effects</subject><subject>Cell Nucleus - metabolism</subject><subject>Cell Proliferation - drug effects</subject><subject>Cellular Reprogramming - drug effects</subject><subject>Colony-Forming Units Assay</subject><subject>Delivery systems</subject><subject>Dentistry</subject><subject>Fibroblasts</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Flow Cytometry</subject><subject>Furans - chemistry</subject><subject>Furans - pharmacology</subject><subject>Genetic Vectors</subject><subject>Humans</subject><subject>Induced pluripotent stem cells</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Induced Pluripotent Stem Cells - metabolism</subject><subject>Intracellular delivery</subject><subject>Mathematical analysis</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Protein transduction</subject><subject>Proteins</subject><subject>Pyridones - chemistry</subject><subject>Pyridones - pharmacology</subject><subject>Recombinant Proteins - metabolism</subject><subject>Reprogramming of fibroblasts</subject><subject>Serum Albumin, Bovine - metabolism</subject><subject>Stem cells</subject><subject>Toxicity</subject><subject>Transfection</subject><subject>Vectors (mathematics)</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk2LFDEQDaK44-pfkODJS4_57O54EGTXL1jw4N5DursyZkx3xiQ9MD9o_6eJs4p4WigIqbz3qlKvEHpFyZYS2r7ZbwcXZpMhOuPTlhHKt6RExx6hDe27vpGKyMdoQ6hgjWopu0DPUtqTcieCPUUXjLdFqCUbdHcN3h0hnnCwOMIhhl008-yWHbZmzCEm7JYcsHVDDIM3KSdsQ8Q7WCCa7MJSiUtYmprJbizwaR1hwge_RncIGZaMU4YZj-B9wmuq2gaPv8kFPwRvzHz47kp4wCaVx6p3dNF4fITaxHP0xJavwov78xLdfvxwe_W5ufn66cvV-5tmlITmRsIgjGJsYLKbjBRKiY6S3ihubD8NRlk6wdRboig1vVW9aCVY2XaCST4Jfolen2XLGH6ukLKeXaptmwXCmjRtBWNCybZ9AJRLwkpxUqBvz9AxhpQiWH2IbjbxpCnR1VC91_8aqquhmpToWCG_vK-zDjNMf6l_HCyA6zMAylyODqJOo4OlOOBimZ2egntYnXf_yYzeFXuM_wEnSPuwxqVyqE5ME_2trlbdLMoJ4Upw_gvAWdFE</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Khan, Majad</creator><creator>Narayanan, Karthikeyan</creator><creator>Lu, Hongfang</creator><creator>Choo, Yang</creator><creator>Du, Chan</creator><creator>Wiradharma, Nikken</creator><creator>Yang, Yi-Yan</creator><creator>Wan, Andrew C.A</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope></search><sort><creationdate>20130701</creationdate><title>Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector</title><author>Khan, Majad ; Narayanan, Karthikeyan ; Lu, Hongfang ; Choo, Yang ; Du, Chan ; Wiradharma, Nikken ; Yang, Yi-Yan ; Wan, Andrew C.A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-5eb4a922b257da549947108a93af8dba9f1ded8f0911a8f98465ef5674253d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Advanced Basic Science</topic><topic>Animals</topic><topic>Biological Assay</topic><topic>Cationic</topic><topic>Cationic bolaamphiphile</topic><topic>Cations</topic><topic>Cattle</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Lineage - drug effects</topic><topic>Cell Nucleus - drug effects</topic><topic>Cell Nucleus - metabolism</topic><topic>Cell Proliferation - drug effects</topic><topic>Cellular Reprogramming - drug effects</topic><topic>Colony-Forming Units Assay</topic><topic>Delivery systems</topic><topic>Dentistry</topic><topic>Fibroblasts</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Flow Cytometry</topic><topic>Furans - chemistry</topic><topic>Furans - pharmacology</topic><topic>Genetic Vectors</topic><topic>Humans</topic><topic>Induced pluripotent stem cells</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Induced Pluripotent Stem Cells - metabolism</topic><topic>Intracellular delivery</topic><topic>Mathematical analysis</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Protein transduction</topic><topic>Proteins</topic><topic>Pyridones - chemistry</topic><topic>Pyridones - pharmacology</topic><topic>Recombinant Proteins - metabolism</topic><topic>Reprogramming of fibroblasts</topic><topic>Serum Albumin, Bovine - metabolism</topic><topic>Stem cells</topic><topic>Toxicity</topic><topic>Transfection</topic><topic>Vectors (mathematics)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, Majad</creatorcontrib><creatorcontrib>Narayanan, Karthikeyan</creatorcontrib><creatorcontrib>Lu, Hongfang</creatorcontrib><creatorcontrib>Choo, Yang</creatorcontrib><creatorcontrib>Du, Chan</creatorcontrib><creatorcontrib>Wiradharma, Nikken</creatorcontrib><creatorcontrib>Yang, Yi-Yan</creatorcontrib><creatorcontrib>Wan, Andrew C.A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Majad</au><au>Narayanan, Karthikeyan</au><au>Lu, Hongfang</au><au>Choo, Yang</au><au>Du, Chan</au><au>Wiradharma, Nikken</au><au>Yang, Yi-Yan</au><au>Wan, Andrew C.A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>34</volume><issue>21</issue><spage>5336</spage><epage>5343</epage><pages>5336-5343</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Protein delivery allows a clinical effect to be directly realized without genetic modification of the host cells. We have developed a cationic bolaamphiphile as a non-viral vector for protein delivery application. The relatively low toxicity and efficient protein delivery by the cationic bolaamphiphile prompted us to test the system for the generation of induced pluripotent stem cells (iPSCs) as an alternative to the conventional vector-based genetic approach. Studies on the kinetics and cytotoxicity of the protein delivery system led us to use an optimized cationic bolaamphiphile-protein complex ratio of 7:1 (wt/wt) and a 3 h period of incubation with human fibroblasts, to ensure complete and non-toxic protein delivery of the reprogramming proteins. The reprogrammed cells were shown to exhibit the characteristics of embryonic stem cells, including expression of pluripotent markers, teratoma formation in SCID mice, and ability to be differentiated into a specific lineage, as exemplified by neuronal differentiation.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>23601660</pmid><doi>10.1016/j.biomaterials.2013.03.072</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0142-9612 |
| ispartof | Biomaterials, 2013-07, Vol.34 (21), p.5336-5343 |
| issn | 0142-9612 1878-5905 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Advanced Basic Science Animals Biological Assay Cationic Cationic bolaamphiphile Cations Cattle Cell Differentiation - drug effects Cell Lineage - drug effects Cell Nucleus - drug effects Cell Nucleus - metabolism Cell Proliferation - drug effects Cellular Reprogramming - drug effects Colony-Forming Units Assay Delivery systems Dentistry Fibroblasts Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Flow Cytometry Furans - chemistry Furans - pharmacology Genetic Vectors Humans Induced pluripotent stem cells Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Intracellular delivery Mathematical analysis Mice Mice, SCID Neurons - cytology Neurons - drug effects Neurons - metabolism Protein transduction Proteins Pyridones - chemistry Pyridones - pharmacology Recombinant Proteins - metabolism Reprogramming of fibroblasts Serum Albumin, Bovine - metabolism Stem cells Toxicity Transfection Vectors (mathematics) |
| title | Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector |
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