Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus
Open accessAbstract
Macroencapsulation devices provide the dual possibility of immunoprotecting transplanted cells while also being retrievable, the latter bearing importance for safety in future trials with stem cell-derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets into patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155 000-180 000 islet equivalents (ie, 1800-4600 islet equivalents per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited (Clinicaltrials.gov: NCT02064309).
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Macroencapsulation devices can promote fibrosis around the implant, further preventing nutrient diffusion.
“these macroencapsulation devices can also promote fibrosis around the implant, further preventing nutrient diffusion.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [92]
The Results (Safety evaluation; page not specified) report fibrotic tissue surrounding the implanted βAir device. The Introduction and Discussion explain that encapsulated islets depend on diffusion for nutrient delivery, but do not say that the surrounding fibrosis further impeded that diffusion. (LLM, conf=0.86)
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BackgroundInfluentialCell delivery systems: Toward the next generation of cell therapies for type 1 diabetes
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“However, lack of direct cell apposition to blood vessels impair mass transport critical for metabolic activity, thus affecting graft viability and function [32,33].”
BackgroundFrom islet of Langerhans transplantation to the bioartificial pancreas
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“Amino acid supplementation during transplantation and devices that can supply oxygen are promising avenues of research (96,97).”
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A steady decline in pancreas transplantation rates
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“Strategies to improve the oxygenation of devices include developing antifibrotic materials ( 29 , 39 , 41 , 42 ), incorporating particles that chemically decompose to release oxygen ( 43 – 46 ), or supplementing oxygen delivery through transcutaneous gas ports ( 47 , 48 ).”
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Development of a Bioartificial Vascular Pancreas
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Safety and function of a new pre-vascularized bioartificial pancreas in an allogeneic rat model
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GPR44 as a Target for Imaging Pancreatic Beta-Cell Mass
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Self-citationRecent advances in endocrine organoids for therapeutic application
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3D Bioprinting and Translation of Beta Cell Replacement Therapies for Type 1 Diabetes
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“36 43 While localized delivery of oxygen and angiogenic factors promote cell viability and vascularization, respectively, measures to protect the cells from rejection such as nanoencapsulation or microencapsulation, localized immunomodulation through controlled drug delivery, or immune engineering…”
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 · see citing works
Artificial Pancreas or Novel Beta-Cell Replacement Therapies: a Race for Optimal Glycemic Control?
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Clinical Applications of Cell Encapsulation Technology
Santos‐Vizcaíno, E., Orive, G., Pedraz, J. L., & Hernández, R. M. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0215-7_32 · Cited by 18 · see citing works
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Applying Immunomodulation to Promote Longevity of Immunoisolated Pancreatic Islet Grafts
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“Four T1D patients received one or two bAir devices with human islets in the subcutaneous site and were monitored for 3–6 months.(38) Although also in this study the safety of the bAir device was demonstrated and islet grafts survived in the devices, only transient levels of circulating C-peptide were observed, while n…”
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Stem cell-derived pancreatic beta cells: a step closer to functional diabetes treatment?
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“An improved variant of the Beta-air device is being generated for hPSC-derived β -cells [51,97].”
β cell replacement therapy for the cure of diabetes
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The Current Status of Bioartificial Pancreas Devices
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“The β air Bio-Artificial Pancreas increases local oxygen availability by directly supplying oxygen via daily injection through a subcutaneous port to the housed islets ( 67 , 68 ).”
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“However, this strategy requires ensuring optimal oxygen and nutrient supply to the encapsulated islets, maintaining the viability and function of the encapsulated islets over time [24].”
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- Authors
- Carlsson, P.-O., Espes, D., Sedigh, A., Rotem, A., Zimerman, B., Grinberg, H., Goldman, T., Barkai, U., Avni, Y., Westermark, G. T., Carlbom, L., Ahlström, H., Eriksson, O., Olerud, J., & Korsgren, O.
- Affiliations
- Uppsala University (SE)
- Beta-O2 Technologies (Israel) (IL)
- Corresponding author
- Carlsson, Per-Ola
- ORCID
- Venue
- American Journal of Transplantation
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 18
- Issue
- 7
- Pages
- 1735-1744
- ISSN
- 1600-6135 (ISSN-L)
- PMC
- PMC6055594
- OpenAlex
- W2777721344
- Cited by
- 205
- References
- 27
- Citations by year
- 2026: 22 · 2025: 15 · 2024: 21 · 2023: 22 · 2022: 23 · 2021: 31 · 2020: 32 · 2019: 26 · 2018: 12 · 2017: 1
- FWCI
- 19.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Transplantation (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Funders
- Juvenile Diabetes Research Foundation International
- Diabetes Research & Wellness Foundation
- Stiftelsen Familjen Ernfors Fond
- Diabetesfonden
- Vetenskapsrådet (921-2014-7054, K2013-55X-15043, K2015-54X-12219-19-4, K2016-01040, K2016-GTW)
- Novo Nordisk
- European Research Council (F4-2013-602889, 646075-ELASTISLET)
- Leona M. and Harry B. Helmsley Charitable Trust
- Barndiabetesfonden
- EXODIAB
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- macroencapsulation, bioartificial pancreas, type 1 diabetes, islet transplantation, oxygen supply, immunoprotection, islet survival, C-peptide, amyloid fibril formation, capsule fibrosis, device retrieval, treatment efficacy and safety
- MeSH terms
- Adolescent, Blood Glucose, Capsules, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Islets of Langerhans, Male, Monitoring, Physiologic, Prognosis, Islets of Langerhans Transplantation, Pancreas, Artificial, Bioartificial Organs
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