Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold
Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized ce...
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| Veröffentlicht in: | Biomaterials 2018-11, Vol.182, p.299-311 |
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| creator | Ng, Soon Seng Saeb-Parsy, Kourosh Blackford, Samuel J.I. Segal, Joe M. Serra, Maria Paola Horcas-Lopez, Marta No, Da Yoon Mastoridis, Sotiris Jassem, Wayel Frank, Curtis W. Cho, Nam Joon Nakauchi, Hiromitsu Glenn, Jeffrey S. Rashid, S. Tamir |
| description | Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications. |
| doi_str_mv | 10.1016/j.biomaterials.2018.07.043 |
| format | Article |
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Tamir</creator><creatorcontrib>Ng, Soon Seng ; Saeb-Parsy, Kourosh ; Blackford, Samuel J.I. ; Segal, Joe M. ; Serra, Maria Paola ; Horcas-Lopez, Marta ; No, Da Yoon ; Mastoridis, Sotiris ; Jassem, Wayel ; Frank, Curtis W. ; Cho, Nam Joon ; Nakauchi, Hiromitsu ; Glenn, Jeffrey S. ; Rashid, S. Tamir</creatorcontrib><description>Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2018.07.043</identifier><identifier>PMID: 30149262</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>adults ; Biocompatible Materials - chemistry ; Bioengineering ; Biomimetic materials ; cell lines ; Cells, Cultured ; collagen ; Crystallization ; gene expression ; human development ; Humans ; induced pluripotent stem cells ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; liver ; Liver - cytology ; Liver stem cells ; mechanical properties ; mice ; Organogenesis ; Organoids - cytology ; pharmacokinetics ; polyethylene glycol ; Polyethylene Glycols - chemistry ; protein secretion ; signal transduction ; therapeutics ; Tissue Engineering - methods ; Tissue Scaffolds - chemistry ; transforming growth factor beta</subject><ispartof>Biomaterials, 2018-11, Vol.182, p.299-311</ispartof><rights>2018 The Authors</rights><rights>Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2018 The Authors 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-28a2d314e1b2e733e832c5d44772da0f415e4505834e38825a29a143c4a806253</citedby><cites>FETCH-LOGICAL-c520t-28a2d314e1b2e733e832c5d44772da0f415e4505834e38825a29a143c4a806253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2018.07.043$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,778,782,883,3539,27907,27908,45978</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30149262$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ng, Soon Seng</creatorcontrib><creatorcontrib>Saeb-Parsy, Kourosh</creatorcontrib><creatorcontrib>Blackford, Samuel J.I.</creatorcontrib><creatorcontrib>Segal, Joe M.</creatorcontrib><creatorcontrib>Serra, Maria Paola</creatorcontrib><creatorcontrib>Horcas-Lopez, Marta</creatorcontrib><creatorcontrib>No, Da Yoon</creatorcontrib><creatorcontrib>Mastoridis, Sotiris</creatorcontrib><creatorcontrib>Jassem, Wayel</creatorcontrib><creatorcontrib>Frank, Curtis W.</creatorcontrib><creatorcontrib>Cho, Nam Joon</creatorcontrib><creatorcontrib>Nakauchi, Hiromitsu</creatorcontrib><creatorcontrib>Glenn, Jeffrey S.</creatorcontrib><creatorcontrib>Rashid, S. Tamir</creatorcontrib><title>Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.</description><subject>adults</subject><subject>Biocompatible Materials - chemistry</subject><subject>Bioengineering</subject><subject>Biomimetic materials</subject><subject>cell lines</subject><subject>Cells, Cultured</subject><subject>collagen</subject><subject>Crystallization</subject><subject>gene expression</subject><subject>human development</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>liver</subject><subject>Liver - cytology</subject><subject>Liver stem cells</subject><subject>mechanical properties</subject><subject>mice</subject><subject>Organogenesis</subject><subject>Organoids - cytology</subject><subject>pharmacokinetics</subject><subject>polyethylene glycol</subject><subject>Polyethylene Glycols - chemistry</subject><subject>protein secretion</subject><subject>signal transduction</subject><subject>therapeutics</subject><subject>Tissue Engineering - methods</subject><subject>Tissue Scaffolds - chemistry</subject><subject>transforming growth factor beta</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkUtv1DAUhSMEokPhLyCLVVkk-Jk4LJCq8ihSJZCAteWxb1KPHHuwk5Gy54fj0ZSqrGBlW-e7597rU1WvCG4IJu2bXbN1cdIzJKd9bigmssFdgzl7VG2I7GQteiweVxtMOK37ltCz6lnOO1zemNOn1Rkrt562dFP9ul4mHZD7-g3Z4ncAi_YpjhDcHFNGpRGE0QWAVBQX5oh8gRKKadQhOpvRkl0Y0dEjFGEumIneF0l7ZNKa53Luo1_RBcy3q4cAaPRrYV6jbPQwRG-fV0-Gsgm8uDvPqx8fP3y_uq5vvnz6fHV5UxtB8VxTqallhAPZUugYA8moEZbzrqNW44ETAVxgIRkHJiUVmvaacGa4lrilgp1X706--2U7gTUQ5qS92ic36bSqqJ36WwnuVo3xoFrCSEe7YnBxZ5DizwXyrCaXDXivA8QlK1o4yTuC2b9R3AtRpiV9Qd-eUJNizgmG-4kIVsfE1U49TFwdE1e4UyXxUvzy4U73pX8iLsD7EwDlZw8OksrGQTBgXQIzKxvd__T5DdMGxmg</recordid><startdate>201811</startdate><enddate>201811</enddate><creator>Ng, Soon Seng</creator><creator>Saeb-Parsy, Kourosh</creator><creator>Blackford, Samuel J.I.</creator><creator>Segal, Joe M.</creator><creator>Serra, Maria Paola</creator><creator>Horcas-Lopez, Marta</creator><creator>No, Da Yoon</creator><creator>Mastoridis, Sotiris</creator><creator>Jassem, Wayel</creator><creator>Frank, Curtis W.</creator><creator>Cho, Nam Joon</creator><creator>Nakauchi, Hiromitsu</creator><creator>Glenn, Jeffrey S.</creator><creator>Rashid, S. Tamir</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>6I.</scope><scope>AAFTH</scope><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>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>201811</creationdate><title>Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold</title><author>Ng, Soon Seng ; Saeb-Parsy, Kourosh ; Blackford, Samuel J.I. ; Segal, Joe M. ; Serra, Maria Paola ; Horcas-Lopez, Marta ; No, Da Yoon ; Mastoridis, Sotiris ; Jassem, Wayel ; Frank, Curtis W. ; Cho, Nam Joon ; Nakauchi, Hiromitsu ; Glenn, Jeffrey S. ; Rashid, S. Tamir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-28a2d314e1b2e733e832c5d44772da0f415e4505834e38825a29a143c4a806253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>adults</topic><topic>Biocompatible Materials - chemistry</topic><topic>Bioengineering</topic><topic>Biomimetic materials</topic><topic>cell lines</topic><topic>Cells, Cultured</topic><topic>collagen</topic><topic>Crystallization</topic><topic>gene expression</topic><topic>human development</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>liver</topic><topic>Liver - cytology</topic><topic>Liver stem cells</topic><topic>mechanical properties</topic><topic>mice</topic><topic>Organogenesis</topic><topic>Organoids - cytology</topic><topic>pharmacokinetics</topic><topic>polyethylene glycol</topic><topic>Polyethylene Glycols - chemistry</topic><topic>protein secretion</topic><topic>signal transduction</topic><topic>therapeutics</topic><topic>Tissue Engineering - methods</topic><topic>Tissue Scaffolds - chemistry</topic><topic>transforming growth factor beta</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ng, Soon Seng</creatorcontrib><creatorcontrib>Saeb-Parsy, Kourosh</creatorcontrib><creatorcontrib>Blackford, Samuel J.I.</creatorcontrib><creatorcontrib>Segal, Joe M.</creatorcontrib><creatorcontrib>Serra, Maria Paola</creatorcontrib><creatorcontrib>Horcas-Lopez, Marta</creatorcontrib><creatorcontrib>No, Da Yoon</creatorcontrib><creatorcontrib>Mastoridis, Sotiris</creatorcontrib><creatorcontrib>Jassem, Wayel</creatorcontrib><creatorcontrib>Frank, Curtis W.</creatorcontrib><creatorcontrib>Cho, Nam Joon</creatorcontrib><creatorcontrib>Nakauchi, Hiromitsu</creatorcontrib><creatorcontrib>Glenn, Jeffrey S.</creatorcontrib><creatorcontrib>Rashid, S. Tamir</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ng, Soon Seng</au><au>Saeb-Parsy, Kourosh</au><au>Blackford, Samuel J.I.</au><au>Segal, Joe M.</au><au>Serra, Maria Paola</au><au>Horcas-Lopez, Marta</au><au>No, Da Yoon</au><au>Mastoridis, Sotiris</au><au>Jassem, Wayel</au><au>Frank, Curtis W.</au><au>Cho, Nam Joon</au><au>Nakauchi, Hiromitsu</au><au>Glenn, Jeffrey S.</au><au>Rashid, S. Tamir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2018-11</date><risdate>2018</risdate><volume>182</volume><spage>299</spage><epage>311</epage><pages>299-311</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>30149262</pmid><doi>10.1016/j.biomaterials.2018.07.043</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | adults Biocompatible Materials - chemistry Bioengineering Biomimetic materials cell lines Cells, Cultured collagen Crystallization gene expression human development Humans induced pluripotent stem cells Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism liver Liver - cytology Liver stem cells mechanical properties mice Organogenesis Organoids - cytology pharmacokinetics polyethylene glycol Polyethylene Glycols - chemistry protein secretion signal transduction therapeutics Tissue Engineering - methods Tissue Scaffolds - chemistry transforming growth factor beta |
| title | Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold |
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