In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how arch...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/133031 |
| _version_ | 1811096109642153984 |
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| author | Stevens, Kelly R. Scull, Margaret A. Ramanan, Vyas Fortin, Chelsea L. Chaturvedi, Ritika R. Knouse, Kristin Ann Xiao, Jing W. Fung, Canny Mirabella, Teodelinda Chen, Amanda X. McCue, Margaret Grace Yang, Michael T. Fleming, Heather Chung, Kwanghun de Jong, Ype P. Chen, Christopher S. Rice, Charles M. Bhatia, Sangeeta N |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Stevens, Kelly R. Scull, Margaret A. Ramanan, Vyas Fortin, Chelsea L. Chaturvedi, Ritika R. Knouse, Kristin Ann Xiao, Jing W. Fung, Canny Mirabella, Teodelinda Chen, Amanda X. McCue, Margaret Grace Yang, Michael T. Fleming, Heather Chung, Kwanghun de Jong, Ype P. Chen, Christopher S. Rice, Charles M. Bhatia, Sangeeta N |
| author_sort | Stevens, Kelly R. |
| collection | MIT |
| description | Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how architecture and scaling may be coupled is needed. We fabricated a structurally organized engineered tissue unit that expanded in response to regenerative cues after implantation into mice with liver injury. Specifically, we found that tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers. There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. We demonstrated the utility of this system for probing the impact of multicellular geometric architecture on tissue expansion in response to liver injury. This approach is a hybrid strategy that harnesses both biology and engineering to more efficiently deploy a limited cell mass after implantation. |
| first_indexed | 2024-09-23T16:38:24Z |
| format | Article |
| id | mit-1721.1/133031 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:38:24Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1330312022-01-18T20:41:41Z In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease Stevens, Kelly R. Scull, Margaret A. Ramanan, Vyas Fortin, Chelsea L. Chaturvedi, Ritika R. Knouse, Kristin Ann Xiao, Jing W. Fung, Canny Mirabella, Teodelinda Chen, Amanda X. McCue, Margaret Grace Yang, Michael T. Fleming, Heather Chung, Kwanghun de Jong, Ype P. Chen, Christopher S. Rice, Charles M. Bhatia, Sangeeta N Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how architecture and scaling may be coupled is needed. We fabricated a structurally organized engineered tissue unit that expanded in response to regenerative cues after implantation into mice with liver injury. Specifically, we found that tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers. There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. We demonstrated the utility of this system for probing the impact of multicellular geometric architecture on tissue expansion in response to liver injury. This approach is a hybrid strategy that harnesses both biology and engineering to more efficiently deploy a limited cell mass after implantation. NIH (Grants R01EB008396, R01DK85713, EB00262, and U24DK059635, P30-CA14051) National Institute of Environmental Health Sciences (Grant P30-ES002109) NIGMS Training (Grant T32GM007753) 2021-10-18T18:08:00Z 2021-10-18T18:08:00Z 2017-07-19 2019-05-09T16:22:31Z Article http://purl.org/eprint/type/JournalArticle 1946-6234 1946-6242 https://hdl.handle.net/1721.1/133031 Stevens, Kelly R., Scull, Margaret A., Ramanan, Vyas, Fortin, Chelsea L., Chaturvedi, Ritika R. et al. 2017. "In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease." Science Translational Medicine, 9 (399). en http://dx.doi.org/10.1126/scitranslmed.aah5505 Science Translational Medicine Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Association for the Advancement of Science (AAAS) PMC |
| spellingShingle | Stevens, Kelly R. Scull, Margaret A. Ramanan, Vyas Fortin, Chelsea L. Chaturvedi, Ritika R. Knouse, Kristin Ann Xiao, Jing W. Fung, Canny Mirabella, Teodelinda Chen, Amanda X. McCue, Margaret Grace Yang, Michael T. Fleming, Heather Chung, Kwanghun de Jong, Ype P. Chen, Christopher S. Rice, Charles M. Bhatia, Sangeeta N In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| title | In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| title_full | In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| title_fullStr | In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| title_full_unstemmed | In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| title_short | In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| title_sort | in situ expansion of engineered human liver tissue in a mouse model of chronic liver disease |
| url | https://hdl.handle.net/1721.1/133031 |
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