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Immunology and Transplantation

Increase Functional β-Cell Mass in Subcutaneous Alginate Capsules With Porcine Prenatal Islet Cells but Loss With Human Adult Islet Cells

  1. Ines De Mesmaeker1,
  2. Thomas Robert1,
  3. Krista G. Suenens1,
  4. Geert M. Stangé1,
  5. Freya Van Hulle1,2,
  6. Zhidong Ling1,2,
  7. Peter Tomme3,
  8. Daniel Jacobs-Tulleneers-Thevissen1,2,
  9. Bart Keymeulen1,2 and
  10. Daniel G. Pipeleers1,2⇑
  1. 1Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
  2. 2University Hospital Brussels–Vrije Universiteit Brussel, Brussels, Belgium
  3. 3Beta Cell NV, Diepenbeek, Belgium
  1. Corresponding author: Daniel G. Pipeleers, daniel.pipeleers{at}vub.be
Diabetes 2018 Dec; 67(12): 2640-2649. https://doi.org/10.2337/db18-0709
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Abstract

Alginate (Alg)-encapsulated porcine islet cell grafts are developed to overcome limitations of human islet transplantation. They can generate functional implants in animals when prepared from fetal, perinatal, and adult pancreases. Implants have not yet been examined for efficacy to establish sustained, metabolically adequate functional β-cell mass (FBM) in comparison with human islet cells. This study in immune-compromised mice demonstrates that subcutaneous implants of Alg-encapsulated porcine prenatal islet cells with 4 × 105 β-cells form, over 10 weeks, a FBM that results in glucose-induced plasma C-peptide >2 ng/mL and metabolic control over the following 10 weeks, with higher efficiency than nonencapsulated, while failing in peritoneum. This intracapsular FBM formation involves β-cell replication, increasing number fourfold, and maturation toward human adult β-cells. Subcutaneous Alg-encapsulated human islet cells with similar β-cell number establish implants with plasma C-peptide >2 ng/mL for the first 10 weeks, with nonencapsulated cells failing; their β-cells do not replicate but progressively die (>70%), explaining C-peptide decline and insufficient metabolic control. An Alg matrix thus helps establish β-cell functions in subcutis. It allows formation of sustained metabolically adequate FBM by immature porcine β-cells with proliferative activity but not by human adult islet cells. These findings define conditions for evaluating its immune-protecting properties.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db18-0709/-/DC1.

  • Received June 28, 2018.
  • Accepted September 25, 2018.
  • © 2018 by the American Diabetes Association.
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Increase Functional β-Cell Mass in Subcutaneous Alginate Capsules With Porcine Prenatal Islet Cells but Loss With Human Adult Islet Cells
Ines De Mesmaeker, Thomas Robert, Krista G. Suenens, Geert M. Stangé, Freya Van Hulle, Zhidong Ling, Peter Tomme, Daniel Jacobs-Tulleneers-Thevissen, Bart Keymeulen, Daniel G. Pipeleers
Diabetes Dec 2018, 67 (12) 2640-2649; DOI: 10.2337/db18-0709

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Increase Functional β-Cell Mass in Subcutaneous Alginate Capsules With Porcine Prenatal Islet Cells but Loss With Human Adult Islet Cells
Ines De Mesmaeker, Thomas Robert, Krista G. Suenens, Geert M. Stangé, Freya Van Hulle, Zhidong Ling, Peter Tomme, Daniel Jacobs-Tulleneers-Thevissen, Bart Keymeulen, Daniel G. Pipeleers
Diabetes Dec 2018, 67 (12) 2640-2649; DOI: 10.2337/db18-0709
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