Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells
Clinical applications of induced pluripotent stem cells (iPSCs) require development of technologies for the production of “footprint-free” (gene integration-free) iPSCs, which avoid the potential risk of insertional mutagenesis in humans. Previously, several studies have shown that mRNA transfer can...
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| Veröffentlicht in: | Journal of controlled release 2016-08, Vol.235, p.222-235 |
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| creator | Choi, Hye Yeon Lee, Tae-Jin Yang, Gwang-Mo Oh, Jaesur Won, Jihye Han, Jihae Jeong, Gun-Jae Kim, Jongpil Kim, Jin-Hoi Kim, Byung-Soo Cho, Ssang-Goo |
| description | Clinical applications of induced pluripotent stem cells (iPSCs) require development of technologies for the production of “footprint-free” (gene integration-free) iPSCs, which avoid the potential risk of insertional mutagenesis in humans. Previously, several studies have shown that mRNA transfer can generate “footprint-free” iPSCs, but these studies did not use a delivery vehicle and thus repetitive daily transfection was required because of mRNA degradation. Here, we report an mRNA delivery system employing graphene oxide (GO)-polyethylenimine (PEI) complexes for the efficient generation of “footprint-free” iPSCs. GO-PEI complexes were found to be very effective for loading mRNA of reprogramming transcription factors and protection from mRNA degradation by RNase. Dynamic suspension cultures of GO-PEI/RNA complexes-treated cells dramatically increased the reprogramming efficiency and successfully generated rat and human iPSCs from adult adipose tissue-derived fibroblasts without repetitive daily transfection. The iPSCs showed all the hallmarks of pluripotent stem cells including expression of pluripotency genes, epigenetic reprogramming, and differentiation into the three germ layers. These results demonstrate that mRNA delivery using GO-PEI-RNA complexes can efficiently generate “footprint-free” iPSCs, which may advance the translation of iPSC technology into the clinical settings.
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| doi_str_mv | 10.1016/j.jconrel.2016.06.007 |
| format | Article |
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[Display omitted]</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2016.06.007</identifier><identifier>PMID: 27266364</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adipose Tissue - cytology ; Alkaline Phosphatase - metabolism ; Cell Differentiation - drug effects ; Cell Survival - drug effects ; Fibroblasts - cytology ; Footprint-free transgene-free ; Gene delivery ; Graphene oxide-polyethylenimine complex ; Graphite - administration & dosage ; HEK293 Cells ; Human induced pluripotent stem cells ; Humans ; Induced Pluripotent Stem Cells - cytology ; Integration-free ; iPSC ; Oxides - administration & dosage ; Polyethyleneimine - administration & dosage ; RNA delivery ; RNA, Messenger - administration & dosage</subject><ispartof>Journal of controlled release, 2016-08, Vol.235, p.222-235</ispartof><rights>2016</rights><rights>Copyright © 2016. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-d72f6051b60b28b60df33734434274f207d8121c440da1ff01d380585f044fa13</citedby><cites>FETCH-LOGICAL-c435t-d72f6051b60b28b60df33734434274f207d8121c440da1ff01d380585f044fa13</cites><orcidid>0000-0002-0968-7932</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2016.06.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27266364$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Hye Yeon</creatorcontrib><creatorcontrib>Lee, Tae-Jin</creatorcontrib><creatorcontrib>Yang, Gwang-Mo</creatorcontrib><creatorcontrib>Oh, Jaesur</creatorcontrib><creatorcontrib>Won, Jihye</creatorcontrib><creatorcontrib>Han, Jihae</creatorcontrib><creatorcontrib>Jeong, Gun-Jae</creatorcontrib><creatorcontrib>Kim, Jongpil</creatorcontrib><creatorcontrib>Kim, Jin-Hoi</creatorcontrib><creatorcontrib>Kim, Byung-Soo</creatorcontrib><creatorcontrib>Cho, Ssang-Goo</creatorcontrib><title>Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Clinical applications of induced pluripotent stem cells (iPSCs) require development of technologies for the production of “footprint-free” (gene integration-free) iPSCs, which avoid the potential risk of insertional mutagenesis in humans. Previously, several studies have shown that mRNA transfer can generate “footprint-free” iPSCs, but these studies did not use a delivery vehicle and thus repetitive daily transfection was required because of mRNA degradation. Here, we report an mRNA delivery system employing graphene oxide (GO)-polyethylenimine (PEI) complexes for the efficient generation of “footprint-free” iPSCs. GO-PEI complexes were found to be very effective for loading mRNA of reprogramming transcription factors and protection from mRNA degradation by RNase. Dynamic suspension cultures of GO-PEI/RNA complexes-treated cells dramatically increased the reprogramming efficiency and successfully generated rat and human iPSCs from adult adipose tissue-derived fibroblasts without repetitive daily transfection. The iPSCs showed all the hallmarks of pluripotent stem cells including expression of pluripotency genes, epigenetic reprogramming, and differentiation into the three germ layers. These results demonstrate that mRNA delivery using GO-PEI-RNA complexes can efficiently generate “footprint-free” iPSCs, which may advance the translation of iPSC technology into the clinical settings.
[Display omitted]</description><subject>Adipose Tissue - cytology</subject><subject>Alkaline Phosphatase - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Fibroblasts - cytology</subject><subject>Footprint-free transgene-free</subject><subject>Gene delivery</subject><subject>Graphene oxide-polyethylenimine complex</subject><subject>Graphite - administration & dosage</subject><subject>HEK293 Cells</subject><subject>Human induced pluripotent stem cells</subject><subject>Humans</subject><subject>Induced Pluripotent Stem Cells - cytology</subject><subject>Integration-free</subject><subject>iPSC</subject><subject>Oxides - administration & dosage</subject><subject>Polyethyleneimine - administration & dosage</subject><subject>RNA delivery</subject><subject>RNA, Messenger - administration & dosage</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFu1DAQhi1ERZfCI4B85JJlHNtx9oSqqrRIFUhVOVvZeNz1KrGD7bTslSevo124Io1seeaf-T0fIR8YrBmw5vN-ve-Djzis6_JcQwlQr8iKtYpXYrORr8mqFNqKN3JzTt6mtAcAyYV6Q85rVTcNb8SK_Lm21vUOfabj_fdLanBwTxgP9NnlHX2M3bRDjzT8dgarKQwHzLvDgN6NrqRtiPSx1GOXXfA02JIJeYrO58pGRLqbx85T583co6HTMEc3hby4pYwj7XEY0jtyZrsh4fvTfUF-fr1-uLqt7n7cfLu6vKt6wWWujKptA5JtG9jWbTmN5VxxIbiolbA1KNOymvVCgOmYtcAMb0G20oIQtmP8gnw6zp1i-DVjynp0aflB5zHMSbOWFXhKClWk8ijtY0gpotVlp7GLB81AL_j1Xp_w6wW_hhKw9H08WczbEc2_rr-8i-DLUYBl0SeHUacFfoHjIvZZm-D-Y_ECqFGbPA</recordid><startdate>20160810</startdate><enddate>20160810</enddate><creator>Choi, Hye Yeon</creator><creator>Lee, Tae-Jin</creator><creator>Yang, Gwang-Mo</creator><creator>Oh, Jaesur</creator><creator>Won, Jihye</creator><creator>Han, Jihae</creator><creator>Jeong, Gun-Jae</creator><creator>Kim, Jongpil</creator><creator>Kim, Jin-Hoi</creator><creator>Kim, Byung-Soo</creator><creator>Cho, Ssang-Goo</creator><general>Elsevier B.V</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>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-0968-7932</orcidid></search><sort><creationdate>20160810</creationdate><title>Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells</title><author>Choi, Hye Yeon ; Lee, Tae-Jin ; Yang, Gwang-Mo ; Oh, Jaesur ; Won, Jihye ; Han, Jihae ; Jeong, Gun-Jae ; Kim, Jongpil ; Kim, Jin-Hoi ; Kim, Byung-Soo ; Cho, Ssang-Goo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-d72f6051b60b28b60df33734434274f207d8121c440da1ff01d380585f044fa13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adipose Tissue - cytology</topic><topic>Alkaline Phosphatase - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Fibroblasts - cytology</topic><topic>Footprint-free transgene-free</topic><topic>Gene delivery</topic><topic>Graphene oxide-polyethylenimine complex</topic><topic>Graphite - administration & dosage</topic><topic>HEK293 Cells</topic><topic>Human induced pluripotent stem cells</topic><topic>Humans</topic><topic>Induced Pluripotent Stem Cells - cytology</topic><topic>Integration-free</topic><topic>iPSC</topic><topic>Oxides - administration & dosage</topic><topic>Polyethyleneimine - administration & dosage</topic><topic>RNA delivery</topic><topic>RNA, Messenger - administration & dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Hye Yeon</creatorcontrib><creatorcontrib>Lee, Tae-Jin</creatorcontrib><creatorcontrib>Yang, Gwang-Mo</creatorcontrib><creatorcontrib>Oh, Jaesur</creatorcontrib><creatorcontrib>Won, Jihye</creatorcontrib><creatorcontrib>Han, Jihae</creatorcontrib><creatorcontrib>Jeong, Gun-Jae</creatorcontrib><creatorcontrib>Kim, Jongpil</creatorcontrib><creatorcontrib>Kim, Jin-Hoi</creatorcontrib><creatorcontrib>Kim, Byung-Soo</creatorcontrib><creatorcontrib>Cho, Ssang-Goo</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>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Hye Yeon</au><au>Lee, Tae-Jin</au><au>Yang, Gwang-Mo</au><au>Oh, Jaesur</au><au>Won, Jihye</au><au>Han, Jihae</au><au>Jeong, Gun-Jae</au><au>Kim, Jongpil</au><au>Kim, Jin-Hoi</au><au>Kim, Byung-Soo</au><au>Cho, Ssang-Goo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2016-08-10</date><risdate>2016</risdate><volume>235</volume><spage>222</spage><epage>235</epage><pages>222-235</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Clinical applications of induced pluripotent stem cells (iPSCs) require development of technologies for the production of “footprint-free” (gene integration-free) iPSCs, which avoid the potential risk of insertional mutagenesis in humans. Previously, several studies have shown that mRNA transfer can generate “footprint-free” iPSCs, but these studies did not use a delivery vehicle and thus repetitive daily transfection was required because of mRNA degradation. Here, we report an mRNA delivery system employing graphene oxide (GO)-polyethylenimine (PEI) complexes for the efficient generation of “footprint-free” iPSCs. GO-PEI complexes were found to be very effective for loading mRNA of reprogramming transcription factors and protection from mRNA degradation by RNase. Dynamic suspension cultures of GO-PEI/RNA complexes-treated cells dramatically increased the reprogramming efficiency and successfully generated rat and human iPSCs from adult adipose tissue-derived fibroblasts without repetitive daily transfection. The iPSCs showed all the hallmarks of pluripotent stem cells including expression of pluripotency genes, epigenetic reprogramming, and differentiation into the three germ layers. These results demonstrate that mRNA delivery using GO-PEI-RNA complexes can efficiently generate “footprint-free” iPSCs, which may advance the translation of iPSC technology into the clinical settings.
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| ispartof | Journal of controlled release, 2016-08, Vol.235, p.222-235 |
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| subjects | Adipose Tissue - cytology Alkaline Phosphatase - metabolism Cell Differentiation - drug effects Cell Survival - drug effects Fibroblasts - cytology Footprint-free transgene-free Gene delivery Graphene oxide-polyethylenimine complex Graphite - administration & dosage HEK293 Cells Human induced pluripotent stem cells Humans Induced Pluripotent Stem Cells - cytology Integration-free iPSC Oxides - administration & dosage Polyethyleneimine - administration & dosage RNA delivery RNA, Messenger - administration & dosage |
| title | Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells |
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