Engineered Matrices Enable the Culture of Human Patient‐Derived Intestinal Organoids
Human intestinal organoids from primary human tissues have the potential to revolutionize personalized medicine and preclinical gastrointestinal disease models. A tunable, fully defined, designer matrix, termed hyaluronan elastin‐like protein (HELP) is reported, which enables the formation, differen...
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| Veröffentlicht in: | Advanced science 2021-05, Vol.8 (10), p.2004705-n/a |
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| creator | Hunt, Daniel R. Klett, Katarina C. Mascharak, Shamik Wang, Huiyuan Gong, Diana Lou, Junzhe Li, Xingnan Cai, Pamela C. Suhar, Riley A. Co, Julia Y. LeSavage, Bauer L. Foster, Abbygail A. Guan, Yuan Amieva, Manuel R. Peltz, Gary Xia, Yan Kuo, Calvin J. Heilshorn, Sarah C. |
| description | Human intestinal organoids from primary human tissues have the potential to revolutionize personalized medicine and preclinical gastrointestinal disease models. A tunable, fully defined, designer matrix, termed hyaluronan elastin‐like protein (HELP) is reported, which enables the formation, differentiation, and passaging of adult primary tissue‐derived, epithelial‐only intestinal organoids. HELP enables the encapsulation of dissociated patient‐derived cells, which then undergo proliferation and formation of enteroids, spherical structures with polarized internal lumens. After 12 rounds of passaging, enteroid growth in HELP materials is found to be statistically similar to that in animal‐derived matrices. HELP materials also support the differentiation of human enteroids into mature intestinal cell subtypes. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization. Organoid formation in HELP materials is most robust in gels with stiffer moduli (G’ ≈ 1 kPa), slower stress relaxation rate (t1/2 ≈ 18 h), and higher integrin ligand concentration (0.5 × 10−3–1 × 10−3 m RGD peptide). This material provides a promising in vitro model for further understanding intestinal development and disease in humans and a reproducible, biodegradable, minimal matrix with no animal‐derived products or synthetic polyethylene glycol for potential clinical translation.
A tunable, designer matrix, termed hyaluronan elastin‐like protein (HELP) that enables the formation, differentiation, and passaging of adult primary tissue‐derived organoids is reported. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization. |
| doi_str_mv | 10.1002/advs.202004705 |
| format | Article |
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A tunable, designer matrix, termed hyaluronan elastin‐like protein (HELP) that enables the formation, differentiation, and passaging of adult primary tissue‐derived organoids is reported. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization.</description><identifier>ISSN: 2198-3844</identifier><identifier>EISSN: 2198-3844</identifier><identifier>DOI: 10.1002/advs.202004705</identifier><identifier>PMID: 34026461</identifier><language>eng</language><publisher>Germany: John Wiley & Sons, Inc</publisher><subject>3D cell culture ; adult stem cells ; Animals ; Biopolymers ; Biopsy ; Cell Differentiation - physiology ; Cell Survival - physiology ; Elastin - chemistry ; engineered biomaterial ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; extracellular matrix ; Extracellular Matrix - chemistry ; Gene expression ; Humans ; Hyaluronic acid ; Hyaluronic Acid - chemistry ; Hydrogels ; Intestinal Mucosa - cytology ; Intestinal Mucosa - metabolism ; intestinal organoid ; Ligands ; Localization ; Mice ; Morphology ; Organoids - cytology ; Organoids - metabolism ; Polyethylene glycol ; Proteins ; Stem cells ; Tissue Engineering - methods</subject><ispartof>Advanced science, 2021-05, Vol.8 (10), p.2004705-n/a</ispartof><rights>2021 The Authors. Advanced Science published by Wiley‐VCH GmbH</rights><rights>2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5570-45daef6267f9940bb920a3786b15615b37301814f768343f05099b193cd547733</citedby><cites>FETCH-LOGICAL-c5570-45daef6267f9940bb920a3786b15615b37301814f768343f05099b193cd547733</cites><orcidid>0000-0002-9801-6304</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132048/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132048/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,2096,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34026461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hunt, Daniel R.</creatorcontrib><creatorcontrib>Klett, Katarina C.</creatorcontrib><creatorcontrib>Mascharak, Shamik</creatorcontrib><creatorcontrib>Wang, Huiyuan</creatorcontrib><creatorcontrib>Gong, Diana</creatorcontrib><creatorcontrib>Lou, Junzhe</creatorcontrib><creatorcontrib>Li, Xingnan</creatorcontrib><creatorcontrib>Cai, Pamela C.</creatorcontrib><creatorcontrib>Suhar, Riley A.</creatorcontrib><creatorcontrib>Co, Julia Y.</creatorcontrib><creatorcontrib>LeSavage, Bauer L.</creatorcontrib><creatorcontrib>Foster, Abbygail A.</creatorcontrib><creatorcontrib>Guan, Yuan</creatorcontrib><creatorcontrib>Amieva, Manuel R.</creatorcontrib><creatorcontrib>Peltz, Gary</creatorcontrib><creatorcontrib>Xia, Yan</creatorcontrib><creatorcontrib>Kuo, Calvin J.</creatorcontrib><creatorcontrib>Heilshorn, Sarah C.</creatorcontrib><title>Engineered Matrices Enable the Culture of Human Patient‐Derived Intestinal Organoids</title><title>Advanced science</title><addtitle>Adv Sci (Weinh)</addtitle><description>Human intestinal organoids from primary human tissues have the potential to revolutionize personalized medicine and preclinical gastrointestinal disease models. A tunable, fully defined, designer matrix, termed hyaluronan elastin‐like protein (HELP) is reported, which enables the formation, differentiation, and passaging of adult primary tissue‐derived, epithelial‐only intestinal organoids. HELP enables the encapsulation of dissociated patient‐derived cells, which then undergo proliferation and formation of enteroids, spherical structures with polarized internal lumens. After 12 rounds of passaging, enteroid growth in HELP materials is found to be statistically similar to that in animal‐derived matrices. HELP materials also support the differentiation of human enteroids into mature intestinal cell subtypes. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization. Organoid formation in HELP materials is most robust in gels with stiffer moduli (G’ ≈ 1 kPa), slower stress relaxation rate (t1/2 ≈ 18 h), and higher integrin ligand concentration (0.5 × 10−3–1 × 10−3 m RGD peptide). This material provides a promising in vitro model for further understanding intestinal development and disease in humans and a reproducible, biodegradable, minimal matrix with no animal‐derived products or synthetic polyethylene glycol for potential clinical translation.
A tunable, designer matrix, termed hyaluronan elastin‐like protein (HELP) that enables the formation, differentiation, and passaging of adult primary tissue‐derived organoids is reported. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization.</description><subject>3D cell culture</subject><subject>adult stem cells</subject><subject>Animals</subject><subject>Biopolymers</subject><subject>Biopsy</subject><subject>Cell Differentiation - physiology</subject><subject>Cell Survival - physiology</subject><subject>Elastin - chemistry</subject><subject>engineered biomaterial</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - metabolism</subject><subject>extracellular matrix</subject><subject>Extracellular Matrix - chemistry</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Hyaluronic acid</subject><subject>Hyaluronic Acid - chemistry</subject><subject>Hydrogels</subject><subject>Intestinal Mucosa - cytology</subject><subject>Intestinal Mucosa - metabolism</subject><subject>intestinal organoid</subject><subject>Ligands</subject><subject>Localization</subject><subject>Mice</subject><subject>Morphology</subject><subject>Organoids - cytology</subject><subject>Organoids - metabolism</subject><subject>Polyethylene glycol</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Tissue Engineering - methods</subject><issn>2198-3844</issn><issn>2198-3844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqFks1uEzEURkcIRKvSLUs0Ehs2Cdf_9gapSkMbqahIQLeWZ8aTOnLsYs-k6o5H6DPyJDikRC0LWNmyj499r7-qeo1gigDwe9Nt8hQDBqAC2LPqECMlJ0RS-vzR_KA6znkFAIgRQZF8WR0QCphTjg6rq3lYumBtsl39yQzJtTbX82Aab-vh2taz0Q9jsnXs6_NxbUL92QzOhuHnj_tTm9ymHFuEwebBBePry7Q0Ibouv6pe9MZne_wwHlXfPs6_zs4nF5dni9nJxaRlTMCEss7YnmMueqUoNI3CYIiQvEGMI9YQQQBJRHvBJaGkBwZKNUiRtmNUCEKOqsXO20Wz0jfJrU2609E4_XshpqU2aXCtt5ohoZBhguCW056CAq6gkZ2gApNetMX1Yee6GZu17dpSZTL-ifTpTnDXehk3WiKCgcoiePcgSPH7WHqi1y631nsTbByzxoyULyDAcUHf_oWu4phKCwslMCWK4UL_i2JYClRq2F473VFtijkn2--fjEBvc6K3OdH7nJQDbx4Xusf_pKIAdAfcOm_v_qPTJ6dXXzCRQH4BOsPF7w</recordid><startdate>20210501</startdate><enddate>20210501</enddate><creator>Hunt, Daniel R.</creator><creator>Klett, Katarina C.</creator><creator>Mascharak, Shamik</creator><creator>Wang, Huiyuan</creator><creator>Gong, Diana</creator><creator>Lou, Junzhe</creator><creator>Li, Xingnan</creator><creator>Cai, Pamela C.</creator><creator>Suhar, Riley A.</creator><creator>Co, Julia Y.</creator><creator>LeSavage, Bauer L.</creator><creator>Foster, Abbygail A.</creator><creator>Guan, Yuan</creator><creator>Amieva, Manuel R.</creator><creator>Peltz, Gary</creator><creator>Xia, Yan</creator><creator>Kuo, Calvin J.</creator><creator>Heilshorn, Sarah C.</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><scope>24P</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>3V.</scope><scope>7XB</scope><scope>88I</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-9801-6304</orcidid></search><sort><creationdate>20210501</creationdate><title>Engineered Matrices Enable the Culture of Human Patient‐Derived Intestinal Organoids</title><author>Hunt, Daniel R. ; Klett, Katarina C. ; Mascharak, Shamik ; Wang, Huiyuan ; Gong, Diana ; Lou, Junzhe ; Li, Xingnan ; Cai, Pamela C. ; Suhar, Riley A. ; Co, Julia Y. ; LeSavage, Bauer L. ; Foster, Abbygail A. ; Guan, Yuan ; Amieva, Manuel R. ; Peltz, Gary ; Xia, Yan ; Kuo, Calvin J. ; Heilshorn, Sarah C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5570-45daef6267f9940bb920a3786b15615b37301814f768343f05099b193cd547733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>3D cell culture</topic><topic>adult stem cells</topic><topic>Animals</topic><topic>Biopolymers</topic><topic>Biopsy</topic><topic>Cell Differentiation - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Advanced science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hunt, Daniel R.</au><au>Klett, Katarina C.</au><au>Mascharak, Shamik</au><au>Wang, Huiyuan</au><au>Gong, Diana</au><au>Lou, Junzhe</au><au>Li, Xingnan</au><au>Cai, Pamela C.</au><au>Suhar, Riley A.</au><au>Co, Julia Y.</au><au>LeSavage, Bauer L.</au><au>Foster, Abbygail A.</au><au>Guan, Yuan</au><au>Amieva, Manuel R.</au><au>Peltz, Gary</au><au>Xia, Yan</au><au>Kuo, Calvin J.</au><au>Heilshorn, Sarah C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Engineered Matrices Enable the Culture of Human Patient‐Derived Intestinal Organoids</atitle><jtitle>Advanced science</jtitle><addtitle>Adv Sci (Weinh)</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>8</volume><issue>10</issue><spage>2004705</spage><epage>n/a</epage><pages>2004705-n/a</pages><issn>2198-3844</issn><eissn>2198-3844</eissn><abstract>Human intestinal organoids from primary human tissues have the potential to revolutionize personalized medicine and preclinical gastrointestinal disease models. A tunable, fully defined, designer matrix, termed hyaluronan elastin‐like protein (HELP) is reported, which enables the formation, differentiation, and passaging of adult primary tissue‐derived, epithelial‐only intestinal organoids. HELP enables the encapsulation of dissociated patient‐derived cells, which then undergo proliferation and formation of enteroids, spherical structures with polarized internal lumens. After 12 rounds of passaging, enteroid growth in HELP materials is found to be statistically similar to that in animal‐derived matrices. HELP materials also support the differentiation of human enteroids into mature intestinal cell subtypes. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization. Organoid formation in HELP materials is most robust in gels with stiffer moduli (G’ ≈ 1 kPa), slower stress relaxation rate (t1/2 ≈ 18 h), and higher integrin ligand concentration (0.5 × 10−3–1 × 10−3 m RGD peptide). This material provides a promising in vitro model for further understanding intestinal development and disease in humans and a reproducible, biodegradable, minimal matrix with no animal‐derived products or synthetic polyethylene glycol for potential clinical translation.
A tunable, designer matrix, termed hyaluronan elastin‐like protein (HELP) that enables the formation, differentiation, and passaging of adult primary tissue‐derived organoids is reported. HELP matrices allow stiffness, stress relaxation rate, and integrin‐ligand concentration to be independently and quantitatively specified, enabling fundamental studies of organoid–matrix interactions and potential patient‐specific optimization.</abstract><cop>Germany</cop><pub>John Wiley & Sons, Inc</pub><pmid>34026461</pmid><doi>10.1002/advs.202004705</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9801-6304</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 3D cell culture adult stem cells Animals Biopolymers Biopsy Cell Differentiation - physiology Cell Survival - physiology Elastin - chemistry engineered biomaterial Epithelial Cells - cytology Epithelial Cells - metabolism extracellular matrix Extracellular Matrix - chemistry Gene expression Humans Hyaluronic acid Hyaluronic Acid - chemistry Hydrogels Intestinal Mucosa - cytology Intestinal Mucosa - metabolism intestinal organoid Ligands Localization Mice Morphology Organoids - cytology Organoids - metabolism Polyethylene glycol Proteins Stem cells Tissue Engineering - methods |
| title | Engineered Matrices Enable the Culture of Human Patient‐Derived Intestinal Organoids |
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