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Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes
Open accessAbstract
Significance: Cell encapsulation holds great potential as a better treatment for type 1 diabetes. An encapsulation system that is scalable to a clinically relevant capacity and can be retrieved or replaced whenever needed is highly desirable for clinical applications. Here we report a cell encapsulation device that is readily scalable and conveniently retrievable through a minimally invasive laparoscopic procedure. We demonstrated its mechanical robustness and facile mass transfer as well as its durable function in diabetic mice. We further showed, as a proof of concept, its scalability and retrievability in dogs. We believe this encapsulation device may contribute to a cellular therapy for type 1 diabetes and potentially other endocrine disorders and hormone-deficient diseases.
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“Rat islets encapsulated within the device were able to survive and reverse diabetes in immune-competent diabetic mice.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [101]
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“For example, in the thread-reinforced alginate fibre for islet encapsulation (TRAFFIC) 110 device, islets are embedded in a thread-like alginate hydrogel that can be laparoscopi-cally retrieved one month after implantation in the abdomen of dogs, for potential replacement with a fresh…”
InfluentialWang, L., Marfil‐Garza, B. A., Ernst, A. U., Pawlick, R. L., Pepper, A. R., Okada, K., Epel, B., Viswakarma, N., Kotecha, M., Flanders, J. A., et al. (2023) · Nature Biomedical Engineering · doi:10.1038/s41551-023-01145-8 · Cited by 38
“Thread-like islet encapsulation devices were fabricated using nylon sutures 43 .”
Self-citationMacroencapsulation Devices for Cell Therapy
Liu, W., Wang, Y., Wang, J., Lanier, O. L., Wechsler, M. E., Peppas, N. A., & Gu, Z. (2022) · Engineering · doi:10.1016/j.eng.2021.10.021 · Cited by 38
Cell‐Surface Engineering for Advanced Cell Therapy
Lee, J. K., Choi, I. S., Oh, T. I., & Lee, E. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201801710 · Cited by 35
Recent trends and advances in type 1 diabetes therapeutics: A comprehensive review
Singh, A. K., Afshan, N., Singh, A., Singh, S. K., Yadav, S., Kumar, M., Sarma, D. K., & Verma, V. (2023) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2023.151329 · Cited by 43
Tissue engineering and 3D printing of bioartificial pancreas for regenerative medicine in diabetes
Soetedjo, A. A. P., Lee, J. M., Lau, H. H., Goh, G. L., An, J., Koh, Y., Yeong, W. Y., & Teo, A. K. K. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.05.007 · Cited by 35
Wang, J.-K., Cheam, N. M. J., Irvine, S., Tan, N., Venkatraman, S., & Tay, C. Y. (2020) · Macromolecular rapid communications · doi:10.1002/marc.202000275 · Cited by 29
Watanabe, T., Okitsu, T., Ozawa, F., Nagata, S., Matsunari, H., Nagashima, H., Nagaya, M., Teramae, H., & Takeuchi, S. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120162 · Cited by 36
Moshref, M., Tangey, B., Gilor, C., Papas, K. K., Williamson, P., Loomba‐Albrecht, L. A., Sheehy, P. A., & Kol, A. (2019) · Stem Cells Translational Medicine · doi:10.1002/sctm.18-0163 · Cited by 38
Engineering Strategies to Improve Islet Transplantation for Type 1 Diabetes Therapy
White, A. M., Shamul, J. G., Xu, J., Stewart, S., Bromberg, J. S., & He, X. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01406 · Cited by 33
A multifunctional decellularized gut suture platform
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Stepwise differentiation of functional pancreatic β cells from human pluripotent stem cells
Jin, W., & Jiang, W. (2022) · Cell Regeneration · doi:10.1186/s13619-022-00125-8 · Cited by 35
Controllable Fabrication of Composite Core–Shell Capsules at a Macroscale as Organoid Biocarriers
He, F., Tao, T., Liu, H., Wang, Y., Cui, K., Guo, Y., & Qin, J. (2021) · ACS Applied Bio Materials · doi:10.1021/acsabm.0c01441 · Cited by 26
Advanced hydrogels for treatment of diabetes
Reyes-Martínez, J. E., Ruiz‐Pacheco, J. A., Flores‐Valdez, M. A., Elsawy, M. A., Vallejo‐Cardona, A. A., & Díaz, L. (2019) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2880 · Cited by 34
Advancements of Biomacromolecular Hydrogel Applications in Food Nutrition and Health
Ye, Z., Sun, L., Xiang, Q., Hao, Y., Liu, H., He, Q. Z., Yang, X., & Liao, W. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c05903 · Cited by 23
Jeang, W., Bochenek, M. A., Bose, S., Zhao, Y.-C., Wong, B. M., Yang, J.-W., Jiang, A. L., Langer, R., & Anderson, D. G. (2024) · Science Advances · doi:10.1126/sciadv.adk5949 · Cited by 22
“To decouple device mechanics from the hydrogel chemistry, other reports pro-pose physically reinforcing hydrogels by integrating solid plastic constructs such as suture-based fiber cores ( 28 ) or external housings based on nanoporous membranes and microfabricated housings ( 29 – 32 ).”
Hydrogel materials for the application of islet transplantation
Xu, L., Guo, Y., Huang, Y. H., Xu, Y., Lu, Y., & Wang, Z. (2019) · Journal of Biomaterials Applications · doi:10.1177/0885328219831391 · Cited by 25
Self-citationPancreatic islet cells in microfluidic-spun hydrogel microfibers for the treatment of diabetes
Huan, Z., Li, J., Guo, J., Yu, Y., & Li, L. (2024) · Acta Biomaterialia · doi:10.1016/j.actbio.2024.08.047 · Cited by 24
A predictive computational platform for optimizing the design of bioartificial pancreas devices
Ernst, A. U., Wang, L., Worland, S. C., Marfil‐Garza, B. A., Wang, X., Liu, W. H., Chiu, A., Kin, T., O’Gorman, D., Steinschneider, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33760-5 · Cited by 30
“A BAP devicepreviously reported byour group 43 was selected asa model encapsulation system for comparing performance when containing an equivalent mass of large fraction islets (LF-BAPs) or small fraction islets (SF-BAPs).”
MethodSelf-citationSouthard, S. M., Kotipatruni, R. P., & Rust, W. L. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203126 · Cited by 27
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“has reported that they were able to retrieve reinforced alginate fiber by laparoscopic surgery in a dog model [21].”
BackgroundReprogramming Cells to Make Insulin
McKimpson, W. M., & Accili, D. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00040 · Cited by 19
“It may be possible to circumvent this need by either the encapsulation of cells [22, 23] or the use of pluripotent stems cells derived directly from T1D patients [24].”
BackgroundYu, G., Zhang, M., Gao, L., Zhou, Y., Qiao, L., Yin, J., Wang, Y., Zhou, J., & Ye, H. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.09.004 · Cited by 24
Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model
Magisson, J., Sassi, A., Xhema, D., Kobalyan, A., Gianello, P., Mourer, B., Tran, N. H., Burcez, C.-T., Bouaoun, R., & Sigrist, S. (2020) · Journal of Tissue Engineering · doi:10.1177/2041731420924818 · Cited by 18
Vitamin C and B3 as new biomaterials to alter intestinal stem cells
Qi, Y., Lohman, J., Bratlie, K. M., Peroutka‐Bigus, N., Bellaire, B. H., Wannemuehler, M. J., Yoon, K. J., Barrett, T. A., & Wang, Q. (2019) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.36715 · Cited by 20
Electrospinning and Cell Fibers in Biomedical Applications
Zhao, Q., Du, X., & Wang, M. (2023) · Advanced Biology · doi:10.1002/adbi.202300092 · Cited by 21
Ruhela, A., Kasinathan, G. N., Rath, S., Sasikala, M., & Sharma, C. (2021) · Materials Science and Engineering C: Materials for Biological Applications · doi:10.1016/j.msec.2020.111409 · Cited by 17
Engineered Biomaterials for Enhanced Function of Insulin‐Secreting β‐Cell Organoids
Hunckler, M. D., & García, A. J. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202000134 · Cited by 24
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Modulating immune responses for enhanced cell therapies: The dual role of multi-scale biomaterials
Zeng, J., Jin, Y., Ao, Y., Li, W., Liang, K., Chen, H., Long, Y., & Du, Y. (2024) · EngMedicine · doi:10.1016/j.engmed.2024.100038 · Cited by 16
Recent advances in endocrine organoids for therapeutic application
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Immunoengineering Biomaterials in Cell-Based Therapy for Type 1 Diabetes
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Generation of Human Stem Cell-Derived Pancreatic Organoids (POs) for Regenerative Medicine
Navarro‐Tableros, V., Gomez, Y., Brizzi, M. F., & Camussi, G. (2019) · Advances in experimental medicine and biology · doi:10.1007/5584_2019_340 · Cited by 17
Clinical Applications of Cell Encapsulation Technology
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Pham, T. T., Tran, P. L., Tempelman, L. A., Stone, S. G., Piccirillo, C., Li, A., Flanders, J. A., & Ma, M. (2025) · Nature Communications · doi:10.1038/s41467-025-62271-2 · Cited by 17
“An increasing body of successful proof-of-concept preclinical studies in mice has demonstrated the potential of this approach to protect encapsulated insulin-secreting cells from immune rejection, thereby enabling long-term glucose homeostasis without the need for immunosuppression 46 – 54 .”
Self-citationHe, W., Li, H., Xu, X., Zhang, X., Chen, J., Lv, C., Yu, H., Feng, Q., & Dong, H. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.152261 · Cited by 15
Metadata
- Authors
- An, D., Chiu, A., Flanders, J. A., Song, W., Shou, D., Lu, Y.-C., Grunnet, L. G., Winkel, L., Ingvorsen, C., Christophersen, N. S., Fels, J. J., Sand, F. W., Ji, Y., Qi, L., Pardo, Y., Luo, D., Silberstein, M., Fan, J., & Ma, M.
- Affiliations
- Cornell University (US)
- Novo Nordisk (Denmark) (DK)
- University of Michigan (US)
- Chinese Academy of Sciences (CN)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-12-26
- Volume
- 115
- Issue
- 2
- Pages
- E263-E272
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5777032
- OpenAlex
- W2776885898
- Cited by
- 200
- References
- 0
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 26 · 2023: 32 · 2022: 22 · 2021: 31 · 2020: 25 · 2019: 32 · 2018: 12
- FWCI
- 19.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020572)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Keywords
- type 1 diabetes, islet transplantation, alginate hydrogel, in situ crosslinking, immunoprotection, retrievability, scalability, human islets, rat islets, cell therapy, C57BL/6 mice, SCID/beige mice
- MeSH terms
- Alginates, Animals, Diabetes Mellitus, Experimental, Dimethylformamide, Dogs, Hexuronic Acids, Humans, Islets of Langerhans, Islets of Langerhans Transplantation, Mice, SCID, Polymethyl Methacrylate, Hydrogels, Glucuronic Acid, Mice, Rats, Cell- and Tissue-Based Therapy
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