In vivo Studies on Insulin Permeability of an Immunoisolation Device Intended for Islet Transplantation Using the Microdialysis Technique
Abstract
In this study, insulin was injected into Theracyte immunoisolation devices to analyze changes in the permeability of the device over time after implantation. The recovery of insulin was studied after subcutaneous implantation of the devices in rats, using the microdialysis technique. The area under the insulin concentration vs. time curves (AUC) after insulin injection in devices implanted 1 day previously did not differ significantly from the AUC after subcutaneous injection. At 1, 2 and 4 weeks after implantation, the recovery of insulin was significantly reduced, but at 3 months, the AUC was not significantly different from that in the control group. Histological examination showed that the number of vascular profiles within 15 microm of the device were significantly higher at 2, 4 weeks and 3 months after transplantation when compared to numbers at 1 week. The design of the device allows transplantation of cells at a chosen time point after its implantation. Delayed filling of the device would allow neovascularization of the device surface before graft implantation and we suggest that such a schedule might improve function of the encapsulated graft.
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Macroencapsulation devices can be limited by a lack of proper nutrient exchange, particularly until vascularization has formed.
“these devices can be limited by a lack of proper nutrient exchange, particularly until vascularization has formed.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [90]
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Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Hogrebe, N. J., Ishahak, M., & Millman, J. R. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.04.002 · Cited by 210 · see citing works
Elliott, R. B., Escobar, L., Tan, P., Garkavenko, O., Calafiore, R., Basta, P., Vasconcellos, A., Emerich, D., Thanos, C., & Bambra, C. (2005) · Transplantation Proceedings · doi:10.1016/j.transproceed.2005.09.038 · Cited by 144 · see citing works
van der Meulen, T., Xie, R., Kelly, O. G., Vale, W., Sander, M., & Huising, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052181 · Cited by 98 · see citing works
Trivedi, N., Steil, G., Colton, C., Bonner-Weir, S., & Weir, G. (2000) · Cell Transplantation · doi:10.1177/096368970000900114 · Cited by 85 · see citing works
“(31) showed that insulin absorp tion from similar devices improves over a period of t ime after S C implantat ion in rats.”
BackgroundSörenby, A., Kumagai-Braesch, M., Sharma, A., Hultenby, K., Wernerson, A., & Tibell, A. (2008) · Transplantation · doi:10.1097/tp.0b013e31817efc78 · Cited by 70 · see citing works
Self-citationDevelopment of an Encapsulated Stem Cell-Based Therapy for Diabetes
Tomei, A., Villa, C., & Ricordi, C. (2015) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2015.1055242 · Cited by 62 · see citing works
“In addition to transport limitations, macrodevices such as the Theracyte device generally induced heavy fibrotic responses at the device--host interface [27,28].”
Tibell, A., Rafael, E., Wennberg, L., Nordenström, J., Bergström, M., Geller, R., Loudovaris, T., Johnson, R. C., Brauker, J., Neuenfeldt, S. K., et al. (2001) · Cell Transplantation · doi:10.3727/000000001783986404 · Cited by 62
Self-citationRafael, E., Wu, G.-S., Hultenby, K., Tibell, A., & Wernerson, A. (2003) · Cell Transplantation · doi:10.3727/000000003108746957 · Cited by 51
Self-citationRafael, E., Wernerson, A., Arner, P., Wu, G.-S., & Tibell, A. (1999) · Cell Transplantation · doi:10.1177/096368979900800302 · Cited by 43
“In a previous study, w e injected insulin into empty TheracyteTM devices p laced SC in rats and compared the recovery of insulin to that after SC injection at var ious t imes after implantat ion of the device (19).”
BackgroundMethodSelf-citationRe-engineering Islet Cell Transplantation
Fotino, N., Fotino, C., & Pileggi, A. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.02.010 · Cited by 41 · see citing works
Encapsulated islet transplantation
Liu, S. S., Shim, S., Kudo, Y., Stabler, C. L., O’Cearbhaill, E. D., Karp, J. M., & Yang, K. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00238-6 · Cited by 41 · see citing works
Transplantable bioartificial pancreas devices: current status and future prospects
Ludwig, B., & Ludwig, S. (2015) · Langenbeck's archives of surgery (Print) · doi:10.1007/s00423-015-1314-y · Cited by 31 · see citing works
Redox-Dependent Inflammation in Islet Transplantation Rejection
Barra, J. M., & Tse, H. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00175 · Cited by 28 · see citing works
“More recently, the development of new technologies including the subcutaneous implantation of islets held within a thin membrane-bound device by TheraCyte can protect insulinproducing cells from the immune system and delay islet allograft rejection (166, 167).”
BackgroundRafael, E., Gazelius, B., Wu, G.-S., & Tibell, A. (2000) · Cell Transplantation · doi:10.1177/096368970000900113 · Cited by 28
“Using microdialysis , we have previously studied the exchange be tween the lumen of the TheraCyteTM device and the circulation in rats at various t imes after implan tation (12,13).”
BackgroundMethodSelf-citationSurvival of pancreatic islet xenografts in NOD mice with the theracyte device.
Yang, Z., Chen, M., Fialkow, L. B., Ellett, J., Wu, R., & Nadler, J. L. (2002) · Transplantation Proceedings · doi:10.1016/s0041-1345(02)03685-0 · Cited by 19 · see citing works
Faleo, G., Lee, K., Nguyen, V., & Tang, Q. (2016) · Transplantation · doi:10.1097/tp.0000000000001146 · Cited by 17 · see citing works
Einstein, S. A., Steyn, L., Weegman, B., Suszynski, T., Sambanis, A., O'Brien, T. D., Avgoustiniatos, E., Firpo, M., Graham, M. L., Janecek, J., et al. (2023) · Frontiers in Transplantation · doi:10.3389/frtra.2023.1257029 · Cited by 10 · see citing works
Considerations for Successful Encapsulated β-Cell Therapy
Thanos, C. G., Gaglia, J. L., & Pagliuca, F. W. (2017) · Molecular and translational medicine · doi:10.1007/978-3-319-57153-9_2 · Cited by 8 · see citing works
“The device was evaluated after 1, 2, 4, and 12 weeks following transplantation, demonstrating that as vascularization of the device progressed, the concentration of insulin in the serum was significantly higher in devices showing high vascular density within 15 μm of the device [101].”
MethodEl-Halawani, S., Gabr, M., El-far, M., Zakaria, M., Khater, S., Refaie, A., & Ghoneim, M. (2020) · Heliyon · doi:10.1016/j.heliyon.2020.e03914 · Cited by 9
“This may represent an important negative aspect of the encapsulation at least using the current material [21, 22].”
BackgroundThe future of islet transplantation beyond the BLA approval: challenges and opportunities
Wang, Y., McGarrigle, J. J., Cook, J., Rios, P., Monica, G. L., Chen, Y., Wei, W., & Oberholzer, J. (2025) · Frontiers in Transplantation · doi:10.3389/frtra.2025.1522409 · Cited by 9 · see citing works
Pancreatic Islet Transplantation Technologies: State of the Art of Micro- and Macro-Encapsulation
Cantarelli, E., Citro, A., & Piemonti, L. (2017) · Current Transplantation Reports · doi:10.1007/s40472-017-0154-9 · Cited by 14 · see citing works
Cell Therapy for T1D Beyond BLA: Gearing Up Toward Clinical Practice
Wang, Y., Chen, Y., McGarrigle, J. J., Cook, J., Rios, P., Monica, G. L., Wei, W., & Oberholzer, J. (2025) · Diabetes Therapy · doi:10.1007/s13300-025-01732-9 · Cited by 5 · see citing works
“It has shown some success in both preclinical and clinical trials, particularly in improving long-term islet survival and function [63–65].”
Steyn, L., Drew, D. A., Vlachos, D. A., Huey, B. L., Cocchi, K., Price, N. D., Johnson, R. C., Putnam, C. W., & Papas, K. (2022) · medRxiv · doi:10.1371/journal.pone.0278794 · Cited by 5 · see citing works
- Authors
- Rafael, E., Wernerson, A., Arner, P., & Tibell, A.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- European Surgical Research
- Publisher
- S. Karger AG
- Published
- 1999
- Volume
- 31
- Issue
- 3
- Pages
- 249-258
- ISSN
- 0014-312X (ISSN-L)
- 1421-9921
- OpenAlex
- W1979506510
- Cited by
- 26
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2020: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2012: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Surgical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet
- Cilag
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- islet transplantation, microdialysis, subcutaneous implantation, neovascularization, vascularization
- MeSH terms
- Animals, Blood Glucose, Fibrosis, Insulin, Male, Permeability, Time Factors, Diffusion Chambers, Culture, Islets of Langerhans Transplantation, Microdialysis, Neovascularization, Physiologic, Area Under Curve, Implants, Experimental, Rats
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