Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 8/2018

01-08-2018 | Immunology, Transplantation, and Regenerative Medicine (L Piemonti and V Sordi, Section Editors)

Transplantation of Macroencapsulated Insulin-Producing Cells

Authors: Albert J. Hwa, Gordon C. Weir

Published in: Current Diabetes Reports | Issue 8/2018

Login to get access

Abstract

Purpose of Review

There is considerable interest in using macroencapsulation devices as a delivery strategy for transplanting insulin-producing cells. This review aims to summarize recent advances, to highlight remaining challenges, and to provide recommendations for the field.

Recent Findings

A variety of new device designs have been reported to improve biocompatibility and to provide protection for islet/beta cells from immune destruction while allowing continuous secretion of insulin. Some of these new approaches are in clinical trials, but more research is needed to determine how sufficient beta-cell mass can be transplanted in a clinically applicable device size, and that insulin is secreted with kinetics that will safely provide adequate controls of glucose levels.

Summary

Macroencapsulation is a potential solution to transplant beta cells without immunosuppression in diabetes patients, but new strategies must be developed to show that this approach is feasible.
Literature
1.
Barton FB, Rickels MR, Alejandro R, Hering BJ, Wease S, Naziruddin B, et al. Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care. 2012;35(7):1436–45.CrossRefPubMedPubMedCentral
2.
Shapiro AM, Pokrywczynska M, Ricordi C. Clinical pancreatic islet transplantation. Nat Rev Endocrinol. 2017;13(5):268–77.CrossRefPubMed
3.
Thompson DM, Meloche M, Ao Z, Paty B, Keown P, Shapiro RJ, et al. Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation. 2011;91(3):373–8.CrossRefPubMed
4.
Thompson DM, Begg IS, Harris C, Ao Z, Fung MA, Meloche RM, et al. Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy. Transplantation. 2008;85(10):1400–5.CrossRefPubMed
5.
Pagliuca FW, Millman JR, Gurtler M, Segel M, Van Dervort A, Ryu JH, et al. Generation of functional human pancreatic beta cells in vitro. Cell. 2014;159(2):428–39.CrossRefPubMedPubMedCentral
6.
Agulnick AD, Ambruzs DM, Moorman MA, Bhoumik A, Cesario RM, Payne JK, et al. Insulin-producing endocrine cells differentiated in vitro from human embryonic stem cells function in macroencapsulation devices in vivo. Stem Cells Transl Med. 2015;4(10):1214–22.CrossRefPubMedPubMedCentral
7.
Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014;32(11):1121–33.CrossRefPubMed
8.
Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, et al. Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J. 2015;34(13):1759–72.CrossRefPubMedPubMedCentral
9.
Liu Z, Hu W, He T, Dai Y, Hara H, Bottino R, et al. Pig-to-primate islet xenotransplantation: past, present, and future. Cell Transplant. 2017;26(6):925–47.CrossRefPubMedPubMedCentral
10.
Chang R, Faleo G, Russ HA, Parent AV, Elledge SK, Bernards DA, et al. Nanoporous immunoprotective device for stem-cell-derived beta-cell replacement therapy. ACS Nano. 2017;11(8):7747–57.CrossRefPubMedPubMedCentral
11.
Donath MY, Boni-Schnetzler M, Ellingsgaard H, Halban PA, Ehses JA. Cytokine production by islets in health and diabetes: cellular origin, regulation and function. Trends Endocrinol Metab. 2010;21(5):261–7.CrossRefPubMed
12.
Kumagai-Braesch M, Jacobson S, Mori H, Jia X, Takahashi T, Wernerson A, et al. The TheraCyte device protects against islet allograft rejection in immunized hosts. Cell Transplant. 2013;22(7):1137–46.CrossRefPubMed
13.
Faleo G, Lee K, Nguyen V, Tang Q. Assessment of immune isolation of allogeneic mouse pancreatic progenitor cells by a macroencapsulation device. Transplantation. 2016;100(6):1211–8.CrossRefPubMedPubMedCentral
14.
Scharp DW, Swanson CJ, Olack BJ, Latta PP, Hegre OD, Doherty EJ, et al. Protection of encapsulated human islets implanted without immunosuppression in patients with type I or type II diabetes and in nondiabetic control subjects. Diabetes. 1994;43:1167–70.CrossRefPubMed
15.
• Carlsson PO, Espes D, Sedigh A, Rotem A, Zimerman B, Grinberg H, et al. Transplantation of macroencapsulated human islets within the bioartificial pancreas beta air to patients with type 1 diabetes mellitus. Am J Transplant. 2017; https://​doi.​org/​10.​1111/​ajt.​14642. This study shows that a macroencapsulation device with a relatively large pore size and exogenous oxygen supply can provide immune protection to allogeneic islets in non-immunosuppressed patients with T1D, but the kinetics of insulin secretion is blunted.
16.
Evron Y, Zimermann B, Ludwig B, Barkai U, Colton CK, Weir GC, et al. Oxygen supply by photosynthesis to an implantable islet cell device. Horm Metab Res. 2015;47(1):24–30.PubMed
17.
Ludwig B, Rotem A, Schmid J, Weir GC, Colton CK, Brendel MD, et al. Improvement of islet function in a bioartificial pancreas by enhanced oxygen supply and growth hormone releasing hormone agonist. Proc Natl Acad Sci U S A. 2012;109(13):5022–7.CrossRefPubMedPubMedCentral
18.
Tuch BE, Keogh GW, Williams LJ, Wu W, Foster JL, Vaithilingam V, et al. Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care. 2009;32(10):1887–9.CrossRefPubMedPubMedCentral
19.
Calafiore R, Basta G, Luca G, Lemmi A, Montanucci MP, Calabrese G, et al. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care. 2006;29(1):137–8.CrossRefPubMed
20.
Paredes-Juarez GA, Sahasrabudhe NM, Tjoelker RS, de Haan BJ, Engelse MA, de Koning EJ, et al. DAMP production by human islets under low oxygen and nutrients in the presence or absence of an immunoisolating-capsule and necrostatin-1. Sci Rep. 2015;5:14623.CrossRefPubMedPubMedCentral
21.
Vegas AJ, Veiseh O, Doloff JC, Ma M, Tam HH, Bratlie K, et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat Biotechnol. 2016;34(3):345–52.CrossRefPubMedPubMedCentral
22.
Vegas AJ, Veiseh O, Gurtler M, Millman JR, Pagliuca FW, Bader AR, et al. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med. 2016;22(3):306–11.CrossRefPubMedPubMedCentral
23.
Veiseh O, Doloff JC, Ma M, Vegas AJ, Tam HH, Bader AR, et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat Mater. 2015;14(6):643–51.CrossRefPubMedPubMedCentral
24.
Colton CK. Oxygen supply to encapsulated therapeutic cells. Adv Drug Deliv Rev. 2014;67-68:93–110.CrossRefPubMed
25.
Coronel MM, Geusz R, Stabler CL. Mitigating hypoxic stress on pancreatic islets via in situ oxygen generating biomaterial. Biomaterials. 2017;129:139–51.CrossRefPubMedPubMedCentral
26.
Bonner-Weir S, Orci L. New perspectives on the microvasculature of the islets of Langerhans in the rat. Diabetes. 1982;31:883–939.CrossRefPubMed
27.
Buchwald P, Tamayo-Garcia A, Manzoli V, Tomei AA, Stabler CL. Glucose-stimulated insulin release: parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets. Biotechnol Bioeng. 2018;115(1):232–45.CrossRefPubMed
28.
Trivedi N, Keegan M, Steil GM, Hollister-Lock J, Hasenkamp WM, Colton CK, et al. Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses. Transplantation. 2001;71(2):203–11.CrossRefPubMed
29.
Omer A, Duvivier-Kali VF, Aschenbach W, Tchipashvili V, Goodyear LJ, Weir GC. Exercise induces hypoglycemia in rats with islet transplantation. Diabetes. 2004;53(2):360–5.CrossRefPubMed
30.
Ludwig B, Reichel A, Steffen A, Zimerman B, Schally AV, Block NL, et al. Transplantation of human islets without immunosuppression. Proc Natl Acad Sci U S A. 2013;110(47):19054–8.CrossRefPubMedPubMedCentral
31.
• Korsgren O. Islet encapsulation: physiological possibilities and limitations. Diabetes. 2017;66(7):1748–54. This review provides more discussions on possible limitations of physiological insulin secretion from encapsulation insulin-producing cells.CrossRefPubMed
32.
Korsgren E, Korsgren O. Glucose effectiveness: the mouse trap in the development of novel ss-cell replacement therapies. Transplantation. 2016;100(1):111–5.CrossRefPubMed
33.
Motte E, Szepessy E, Suenens K, Stange G, Bomans M, Jacobs-Tulleneers-Thevissen D, et al. Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts. Am J Physiol Endocrinol Metab. 2014;307(9):E838–46.CrossRefPubMed
34.
• Robert T, De Mesmaeker I, Stange GM, Suenens KG, Ling Z, Kroon EJ, et al. Functional beta cell mass from device-encapsulated hESC-derived pancreatic endoderm achieving metabolic control. Stem Cell Rep. 2018;10(3):739–50. This report, coupled with their earlier 2014 paper, shows that the outcome of encapsulated stem cell-derived insulin-producing cell products can change based on the types of encapsulation technology. Detailed analysis of beta-cell number and the insulin content and secretion on a per-cell basis is critically important to assess the functional beta-cell mass over time.CrossRef
35.
Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 2008;26(4):443–52.CrossRefPubMed
36.
Maki T, Otsu I, O'Neil JJ, Dunleavy K, Mullon CJ, Solomon BA, et al. Treatment of diabetes by xenogeneic islets without immunosuppression. Use of a vascularized bioartificial pancreas. Diabetes. 1996;45:342–7.CrossRefPubMed
37.
Song S, Yeung R, Park J, Posselt AM, Desai TA, Tang Q, et al. Glucose-stimulated insulin response of silicon nanopore-immunoprotected islets under convective transport. ACS Biomater Sci Eng. 2017;3(6):1051–61.CrossRefPubMedPubMedCentral
38.
Weaver JD, Headen DM, Aquart J, Johnson CT, Shea LD, Shirwan H, et al. Vasculogenic hydrogel enhances islet survival, engraftment, and function in leading extrahepatic sites. Sci Adv. 2017;3(6):e1700184.CrossRefPubMedPubMedCentral
39.
Vlahos AE, Cober N, Sefton MV. Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets. Proc Natl Acad Sci U S A. 2017;114(35):9337–42.CrossRefPubMedPubMedCentral
40.
Sorenby AK, Kumagai-Braesch M, Sharma A, Hultenby KR, Wernerson AM, Tibell AB. Preimplantation of an immunoprotective device can lower the curative dose of islets to that of free islet transplantation: studies in a rodent model. Transplantation. 2008;86(2):364–6.CrossRefPubMed
41.
Rafael E, Wu GS, Hultenby K, Tibell A, Wernerson A. Improved survival of macroencapsulated islets of Langerhans by preimplantation of the immunoisolating device: a morphometric study. Cell Transplant. 2003;12(4):407–12.CrossRefPubMed
42.
An D, Chiu A, Flanders JA, Song W, Shou D, Lu YC, et al. Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes. Proc Natl Acad Sci U S A. 2018;115(2):E263–e72.CrossRefPubMed
43.
Gurlin RE, Keating MT, Li S, Lakey JR, de Feraudy S, Shergill BS, et al. Vascularization and innervation of slits within polydimethylsiloxane sheets in the subcutaneous space of athymic nude mice. J Tissue Eng 2017;8:2041731417691645.
44.
Frei AW, Li Y, Jiang K, Buchwald P, Stabler CL. Local delivery of fingolimod from three-dimensional scaffolds impacts islet graft efficacy and microenvironment in a murine diabetic model. J Tissue Eng Regen Med. 2018;12(2):393–404.CrossRefPubMed
45.
Pepper AR, Pawlick R, Gala-Lopez B, MacGillivary A, Mazzuca DM, White DJ, et al. Diabetes is reversed in a murine model by marginal mass syngeneic islet transplantation using a subcutaneous cell pouch device. Transplantation. 2015;99(11):2294–300.CrossRefPubMedPubMedCentral
46.
BL G-L, Pepper AR, Dinyari P, Malcolm AJ, Kin T, Pawlick LR, et al. Subcutaneous clinical islet transplantation in a prevascularized subcutaneous pouch—preliminary experience. CellR4. 2016;4(5):e2132.
47.
Pepper AR, Bruni A, Pawlick RL, Gala-Lopez B, Rafiei Y, Wink J, et al. Long-term function and optimization of mouse and human islet transplantation in the subcutaneous device-less site. Islets. 2016;8:1–9.CrossRef
48.
Pepper AR, Pawlick R, Bruni A, Wink J, Rafiei Y, O'Gorman D, et al. Transplantation of human pancreatic endoderm cells reverses diabetes post transplantation in a prevascularized subcutaneous site. Stem Cell Rep. 2017;8(6):1689–700.CrossRef
Metadata
Title
Transplantation of Macroencapsulated Insulin-Producing Cells
Authors
Albert J. Hwa
Gordon C. Weir
Publication date
01-08-2018
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 8/2018
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-018-1028-y

Other articles of this Issue 8/2018

Current Diabetes Reports 8/2018 Go to the issue

Pediatric Type 2 and Monogenic Diabetes (PS Zeitler and O Pinhas-Hamiel, Section Editors)

Methods for Measuring Risk for Type 2 Diabetes in Youth: the Oral Glucose Tolerance Test (OGTT)

Pediatric Type 2 and Monogenic Diabetes (PS Zeitler and O Pinhas-Hamiel, Section Editors)

Monogenic Diabetes in Children and Adolescents: Recognition and Treatment Options

Genetics (AP Morris, Section Editor)

Shared Genetic Contribution of Type 2 Diabetes and Cardiovascular Disease: Implications for Prognosis and Treatment

Diabetes Epidemiology (E Selvin and K Foti, Section Editors)

Availability and Affordability of Essential Medicines: Implications for Global Diabetes Treatment

Diabetes Epidemiology (E Selvin and K Foti, Section Editors)

Diabetes Among Non-Overweight Individuals: an Emerging Public Health Challenge

Hospital Management of Diabetes (A Wallia and JJ Seley, Section Editors)

Strategies to Prevent Readmission in High-Risk Patients with Diabetes: the Importance of an Interdisciplinary Approach
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits