A therapeutic convection–enhanced macroencapsulation device for enhancing β cell viability and insulin secretion
Open accessAbstract
Significance: Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β cells and it burdens millions worldwide. T1D patients typically require the life-long administration of insulin or immunosuppressive agents following transplantation. A macroencapsulation device (MED) acts as a bioartificial pancreas and can immunoprotect encapsulated β cells. However, conventional MEDs suffer from limited, cell-loading capacity and slow, glucose-stimulated insulin secretion (GSIS) because of the sole reliance on diffusion. Here, we developed a convection-enhanced MED (ceMED) to afford 3D capsule geometry for maximized cell loading and faster GSIS driven by convection. Overall, we demonstrated that the ceMED significantly improves nutrient exchange that enhances cell viability and GSIS, ultimately leading to a rapid reduction of hyperglycemia.
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A PTFE macroencapsulation device that actively pumped fluid through a hollow fiber running through its center demonstrated enhanced nutrient exchange that promoted cell survival and allowed for a greater cell density to be successfully loaded into the device.
“For example, a PTFE macroencapsulation device that actively pumped fluid through a hollow fiber running through its center demonstrated enhanced nutrient exchange that promoted cell survival and allowed for a greater cell density to be successfully loaded into the device.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [94]
Insulin secretion and blood glucose control were enhanced when the active fluid flow device was transplanted into diabetic rats.
“Insulin secretion and blood glucose control was also enhanced when transplanted into diabetic rats.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [94]
A decreased fibrotic response was observed with the active fluid flow setup.
“Interestingly, they also observed a decreased fibrotic response with their active fluid flow setup.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [94]
Relying on active fluid flow rather than passive diffusion for nutrient transport can greatly enhance the viability and performance of islets within a macroencapsulation device.
“this study highlights that relying on active fluid flow rather than passive diffusion for nutrient transport can greatly enhance the viability and performance of islets within a macroencapsulation device.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [94]
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Self-citationCell delivery systems: Toward the next generation of cell therapies for type 1 diabetes
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“However, shortage of donors and immune rejection are the major concerns associated with islet transplantation [76, 77].”
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“…bed by Technion, an oxygenation cell delivery device from Procyon Technologies, and an electrospun nanofibrous encapsulation device from Novo Nordisk are some examples of potential encapsulation devices that may reduce the dependency on immunosuppressive treatments in the future [58,122–125].”
From cold chain to ambient: Benefits, risks, and evidence across cell therapy logistics
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“173 Due to their ability to provide structural support and offer a porous and diffusible environment and their versatility (natural vs. synthetic, stiffness, matrix-interactions, etc.), 174 hydro-gel-based systems have been used to encapsulate and transport various cell types, serving as an…”
Improving the 3D Printability of Sugar Glass to Engineer Sacrificial Vascular Templates
Moeun, B., Fernandez, S., Collin, S., Gauvin-Rossignol, G., Lescot, T., Fortin, M., Ruel, J., Bégin-Drolet, A., Leask, R., & Hoesli, C. (2022) · 3D Printing and Additive Manufacturing · doi:10.1089/3dp.2021.0147 · Cited by 12
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“17 Additionally, concerns over tumorigenicity and immune safety further complicate clinical applications.”
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“Our previous study confirmed that convective flow significantly enhances metabolic substrate transport compared to passive diffusion [16].”
InfluentialSelf-citationCharacterization of human islet function in a convection‐driven intravascular bioartificial pancreas
Santandreu, A., Taheri-Tehrani, P., Feinberg, B., Torres, A., Blaha, C. A., Shaheen, R., Moyer, J. C., Wright, N., Szot, G., Fissell, W., et al. (2022) · Bioengineering & Translational Medicine · doi:10.1002/btm2.10444 · Cited by 5 · see citing works
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Self-citationRole of Cell-Based Therapies in T2D
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The road ahead for applications of mechanics in drug delivery
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Microvessels enhance vascularization and function of transplanted insulin-producing cells.
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“Contemporary systems such as Encaptra ® and β Air ® integrate oxygenation modules or vascularization-promoting coatings to mitigate diffusion constraints inherent in larger implants [108,109].”
Advancing diabetes treatment: from human beta cell technology to bioartificial pancreas development
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Defining the chromatin and transcriptional landscape of stem cell-derived islets
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A micro-organ based microfluidic biosensor for continuous monitoring of glucose levels in vivo
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“As islet encapsulation techniques are constantly evolving, direct implantation of such a device may eventually be possible in the future 57 .”
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“To address the challenges associated with passive diffusion, some approaches have used a refillable oxygen chamber 15 , oxygen generating materials 16 , an external pump for convective transfer 17 or ultrafiltration 18,19 .”
BackgroundMethodDiabetes treatment by conversion of gut epithelial cells to insulin‐producing cells
Accili, D., Talchai, S. C., Bouchi, R., Lee, A. Y., Du, W. J., Kitamoto, T., McKimpson, W. M., Belvedere, S., & Lin, H. V. (2024) · Journal of Diabetes Investigation · doi:10.1111/jdi.14175 · Cited by 2 · see citing works
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“For example, β-cell therapeutics often face challenges related to hypoxia and subsequent cell death due to inadequate vascularization to support the survival of transplants, especially in the early stages after transplantation [17].”
BackgroundStem cell therapies for treatment of diabetes mellitus
Guo, F., Song, Y., & Qin, G. (2026) · Chinese Medical Journal · doi:10.1097/cm9.0000000000004150 · Cited by 1 · see citing works
“[74] In addition, genetic engineering techniques can be used to overcome immune rejection challenges.”
Engineering the oxygen microenvironment for pancreatic islet transplants
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“Extravascular approaches utilizing external pumps or syringes for fl uid perfusion 134,135 similarly improved islet viability compared to non-perfused controls.”
Brassard, J. A., Sidharthan, D. S., Orimi, H. E., Ling, S. D., Vdovenko, D., Rioux, Y., Wang, H., Campeau, M.-A., Champion, K. S., Lemaire, F., et al. (2026) · Cell Biomaterials · doi:10.1016/j.celbio.2026.100455
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“Recent studies have demonstrated that NET components can directly impair β -cell viability and insulin secretion in vitro, 17,18 while animal models show that genetic or pharmacologic inhibition of NETosis can preserve β -cell mass and improve glycemic control.”
Bioengineering of vascular macrodevices for transplantation of insulin-producing cells
Karami, M., Halvaei, M., Royaei, R., Tahamtani, Y., & Ashtiani, M. K. (2026) · Trends in biotechnology · doi:10.1016/j.tibtech.2025.11.020
Thomson, E. A., Lee, S., Xu, H., Moeller, H. P., Sands, J., Lal, R., Annes, J. P., & Poon, A. S. Y. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.11.570688
“Potential techniques include the direct injection of oxygen into the device, similar to the βAir device 13,14,31,32 , pump-based extravascular convection-enhanced methods 33 , prevascularization of graft sites 35 , and in situ oxygen generation methods 36–41 .”
MethodReversing Type 1 Diabetes: The Magnifying Potential of Stem Cell Encapsulation
Bagherian, A., Jain, A., Prathap, D., & Nguyen, V.-L. (2022) · Berkeley Pharma Tech Journal of Medicine · doi:10.52243/bptjm.v1i2.27
- Authors
- Yang, K., O’Cearbhaill, E. D., Liu, S. S., Zhou, A., Chitnis, G. D., Hamilos, A. E., Xu, J., Verma, M. K. S., Giraldo, J. A., Kudo, Y., Lee, E. A., Lee, Y., Pop, R., Langer, R., Melton, D. A., Greiner, D. L., & Karp, J. M.
- Affiliations
- Broad Institute (US)
- University College Dublin (IE)
- Brigham and Women's Hospital (US)
- Breakthrough T1D (US)
- Harvard University (US)
- Harvard–MIT Division of Health Sciences and Technology, Cambridge, MA 02139;
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Karp, Jeffrey M.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-09-09
- Volume
- 118
- Issue
- 37
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8449352
- OpenAlex
- W3197355082
- Cited by
- 58
- References
- 59
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 13 · 2023: 13 · 2022: 13 · 2021: 2
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- HHS | National Institutes of Health (HL095722, U01DK104218)
- Juvenile Diabetes Research Foundation (3-SRA-2013-282)
- Incheon National University (Research Grant in 2021)
- 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, type 1 diabetes, beta-cell viability, insulin secretion, glucose-stimulated insulin secretion, immunoprotection, hyperglycemia, glucose tolerance, fibrosis
- MeSH terms
- Insulin Secretion, Cell Encapsulation, Animals, Cell Survival, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Insulin, Islets of Langerhans, Male, Islets of Langerhans Transplantation, Drug Delivery Systems, Convection, Insulin-Secreting Cells, Rats
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