Supporting Survival of Transplanted Stem-Cell-Derived Insulin-Producing Cells in an Encapsulation Device Augmented with Controlled Release of Amino Acids

Gauree S. Chendke, Gaetano Faleo, Charity Juang, Audrey V. Parent, Daniel A. Bernards, Matthias Hebrok, Qizhi Tang, Tejal A. Desai

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Pancreatic islet transplantation is a promising treatment for type I diabetes, which is a chronic autoimmune disease in which the host immune cells attack insulin-producing beta cells. The impact of this therapy is limited due to tissue availability and dependence on immunosuppressive drugs that prevent immune rejection of the transplanted cells. These issues can be solved by encapsulating stem cell-derived insulin-producing cells in an immunoprotective device. However, encapsulation exacerbates ischemia, and the lack of vasculature at the implantation site post-transplantation worsens graft survival. Here, an encapsulation device that supplements nutrients to the cells is developed to improve the survival of encapsulated stem cell-derived insulin-producing cells in the poorly vascularized subcutaneous space. An internal compartment in the device is fabricated to provide zero-order release of alanine and glutamine for several weeks. The amino acid reservoir sustains viability of insulin-producing cells in nutrient limiting conditions in vitro. Moreover, the reservoir also increases cell survival by 30% after transplanting the graft in the subcutaneous space.

Original languageEnglish
Article number1900086
JournalAdvanced Biosystems
Volume3
Issue number9
DOIs
StatePublished - 1 Sep 2019
Externally publishedYes

Keywords

  • beta cell replacement therapy
  • cell encapsulation device
  • nanotechnology
  • transplantation
  • type 1 diabetes

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