Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome
Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2015-01-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368913X673469 |
| _version_ | 1818342348398002176 |
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| author | Daria Zorzi Tammy Phan Marco Sequi Yong Lin Daniel H. Freeman Luca Cicalese Cristiana Rastellini M.D. |
| author_facet | Daria Zorzi Tammy Phan Marco Sequi Yong Lin Daniel H. Freeman Luca Cicalese Cristiana Rastellini M.D. |
| author_sort | Daria Zorzi |
| collection | DOAJ |
| description | Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 μm; medium 150–300 μm; small, <150 μm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome. |
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| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T16:13:16Z |
| publishDate | 2015-01-01 |
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| series | Cell Transplantation |
| spelling | doaj.art-c8e6f8c0336145a188a1d56ed83911ef2022-12-21T23:38:53ZengSAGE PublishingCell Transplantation0963-68971555-38922015-01-012410.3727/096368913X673469Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve OutcomeDaria Zorzi0Tammy Phan1Marco Sequi2Yong Lin3Daniel H. Freeman4Luca Cicalese5Cristiana Rastellini M.D.6 Department of Surgery, Texas Transplant Center, University of Texas Medical Branch, Galveston, TX, USA Department of Surgery, Texas Transplant Center, University of Texas Medical Branch, Galveston, TX, USA Laboratory for Mother and Child Health, Department of Public Health, “Mario Negri” Pharmacological Research Institute, Milan, Italy Department of Surgery, Texas Transplant Center, University of Texas Medical Branch, Galveston, TX, USA Department of Epidemiology and Biostatistics, University of Texas Medical Branch, Galveston, TX, USA Department of Surgery, Texas Transplant Center, University of Texas Medical Branch, Galveston, TX, USA Department of Surgery, Texas Transplant Center, University of Texas Medical Branch, Galveston, TX, USABetter results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 μm; medium 150–300 μm; small, <150 μm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical outcome.https://doi.org/10.3727/096368913X673469 |
| spellingShingle | Daria Zorzi Tammy Phan Marco Sequi Yong Lin Daniel H. Freeman Luca Cicalese Cristiana Rastellini M.D. Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome Cell Transplantation |
| title | Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome |
| title_full | Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome |
| title_fullStr | Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome |
| title_full_unstemmed | Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome |
| title_short | Impact of Islet Size on Pancreatic Islet Transplantation and Potential Interventions to Improve Outcome |
| title_sort | impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome |
| url | https://doi.org/10.3727/096368913X673469 |
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