Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice
Islet transplantation as a therapy or cure for type 1 diabetes has significant promise but has been limited by islet mass requirements and long-term graft failure. The intrahepatic and intravascular site may be responsible for significant loss of transplanted islets. Nonencapsulating biomaterial sca...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2013-05-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X636966 |
| _version_ | 1818870718134222848 |
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| author | Romie F. Gibly Xiaomin Zhang William L. Lowe Lonnie D. Shea |
| author_facet | Romie F. Gibly Xiaomin Zhang William L. Lowe Lonnie D. Shea |
| author_sort | Romie F. Gibly |
| collection | DOAJ |
| description | Islet transplantation as a therapy or cure for type 1 diabetes has significant promise but has been limited by islet mass requirements and long-term graft failure. The intrahepatic and intravascular site may be responsible for significant loss of transplanted islets. Nonencapsulating biomaterial scaffolds provide a strategy for architecturally defining and modulating extrahepatic sites beyond the endogenous milieu to enhance islet survival and function. We utilized scaffolds to transplant human islets into the intraperitoneal fat of immunodeficient mice. A smaller human islet mass than previously reported reversed murine diabetes and restored glycemic control at human blood glucose levels. Graft function was highly dependent on the islet number transplanted and directly correlated to islet viability, as determined by the ATP-to-DNA ratio. Islets engrafted and revascularized in host tissue, and glucose tolerance testing indicated performance equivalent to healthy mice. Addition of extracellular matrix, specifically collagen I V, to scaffold surfaces improved graft function compared to serum-supplemented media. Porous scaffolds can facilitate efficient human islet transplantation and provide a platform for modulating the islet microenvironment, in ways not possible with current clinical strategies, to enhance islet engraftment and function. |
| first_indexed | 2024-12-19T12:11:28Z |
| format | Article |
| id | doaj.art-3f18a5ef3df54e8fbc9ff5e29fb4d245 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-19T12:11:28Z |
| publishDate | 2013-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-3f18a5ef3df54e8fbc9ff5e29fb4d2452022-12-21T20:22:10ZengSAGE PublishingCell Transplantation0963-68971555-38922013-05-012210.3727/096368912X636966Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in MiceRomie F. Gibly0Xiaomin Zhang1William L. Lowe2Lonnie D. Shea3Integrated Graduate Program, Northwestern University, Chicago, IL, USADepartment of Surgery, Northwestern University, Chicago, IL, USADepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USADepartment of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USAIslet transplantation as a therapy or cure for type 1 diabetes has significant promise but has been limited by islet mass requirements and long-term graft failure. The intrahepatic and intravascular site may be responsible for significant loss of transplanted islets. Nonencapsulating biomaterial scaffolds provide a strategy for architecturally defining and modulating extrahepatic sites beyond the endogenous milieu to enhance islet survival and function. We utilized scaffolds to transplant human islets into the intraperitoneal fat of immunodeficient mice. A smaller human islet mass than previously reported reversed murine diabetes and restored glycemic control at human blood glucose levels. Graft function was highly dependent on the islet number transplanted and directly correlated to islet viability, as determined by the ATP-to-DNA ratio. Islets engrafted and revascularized in host tissue, and glucose tolerance testing indicated performance equivalent to healthy mice. Addition of extracellular matrix, specifically collagen I V, to scaffold surfaces improved graft function compared to serum-supplemented media. Porous scaffolds can facilitate efficient human islet transplantation and provide a platform for modulating the islet microenvironment, in ways not possible with current clinical strategies, to enhance islet engraftment and function.https://doi.org/10.3727/096368912X636966 |
| spellingShingle | Romie F. Gibly Xiaomin Zhang William L. Lowe Lonnie D. Shea Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice Cell Transplantation |
| title | Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice |
| title_full | Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice |
| title_fullStr | Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice |
| title_full_unstemmed | Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice |
| title_short | Porous Scaffolds Support Extrahepatic Human Islet Transplantation, Engraftment, and Function in Mice |
| title_sort | porous scaffolds support extrahepatic human islet transplantation engraftment and function in mice |
| url | https://doi.org/10.3727/096368912X636966 |
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