ATC Abstracts

American Transplant Congress abstracts

  • Home
  • Meetings Archive
    • 2022 American Transplant Congress
    • 2021 American Transplant Congress
    • 2020 American Transplant Congress
    • 2019 American Transplant Congress
    • 2018 American Transplant Congress
    • 2017 American Transplant Congress
    • 2016 American Transplant Congress
    • 2015 American Transplant Congress
    • 2013 American Transplant Congress
  • Keyword Index
  • Resources
    • 2021 Resources
    • 2016 Resources
      • 2016 Welcome Letter
      • ATC 2016 Program Planning Committees
      • ASTS Council 2015-2016
      • AST Board of Directors 2015-2016
    • 2015 Resources
      • 2015 Welcome Letter
      • ATC 2015 Program Planning Committees
      • ASTS Council 2014-2015
      • AST Board of Directors 2014-2015
      • 2015 Conference Schedule
  • Search

Engineered Adaptable Human Endothelial Cells Enable Durable Engraftment of Subcutaneously Transplanted Islets

R. Craig-Schapiro, G. Li, S. Rafii

Weill Cornell Medical College, New York, NY

Meeting: 2022 American Transplant Congress

Abstract number: 1519

Keywords: Endothelial cells, Hyperglycemia, Islets, Mice, SCID

Topic: Basic Science » Basic Science » 05 - Translational Cellular Therapies: Islet and Stem Cell Transplantation

Session Information

Session Name: Translational Cellular Therapies: Islet and Stem Cell Transplantation

Session Type: Poster Abstract

Date: Tuesday, June 7, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: The current clinical practice of islet transplantation into the portal vein is suboptimal, with reduced vascularization limiting successful engraftment and the inability for monitoring and retrieval of grafts. The subcutaneous site, however, has posed a challenge for transplantation as it is an inhospitable environment for islets to acquire rapid, nurturing blood supply. Endothelial cells (ECs) can provide an instructive tissue-specific vascular niche that fosters islet homeostasis and survival. Adult ECs, however, lack the plasticity and ability to interact with islets; thus, we have engineered adaptable endothelium.

*Methods: By transient transduction of ETS variant transcription factor 2 we have reprogrammed adult human ECs to an adaptable tubulogenic state (R-VECs). These R-VECs form perfusable vascular plexi and avidly arborize islets within microfluidic devices.

*Results: In microfluidic devices, human islets arborized by R-VECs respond to glucose stimulation delivered through the inlet chamber and secrete insulin detected in the outlet chamber. Due to the rich, expedited vascularization from R-VECs, subcutaneously transplanted human islets achieve euglycemia for >12 weeks in streptozotocin-induced diabetic SCID-Beige mice, while transplantation with islets alone or islets with generic ECs do not. Furthermore, diabetic mice transplanted with R-VEC/islets demonstrate body weight stabilization and improved glucose tolerance. Grafts that were retrieved one month after transplantation showed vascularized engraftment only with R-VEC/islets and not with islets alone or islets with generic ECs. Single cell RNA-sequencing of R-VECs after co-culture with human islets reveals gene expression changes suggesting R-VECs adapt to islets and may acquire an islet-specific endothelial phenotype.

*Conclusions: Pre-vascularization of islets with R-VECs provides a specialized vascular niche that supports the engraftment and survival of transplanted islets in the subcutaneous space, avoiding complications associated with intraportal infusion.

  • Tweet
  • Email
  • Print

To cite this abstract in AMA style:

Craig-Schapiro R, Li G, Rafii S. Engineered Adaptable Human Endothelial Cells Enable Durable Engraftment of Subcutaneously Transplanted Islets [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/engineered-adaptable-human-endothelial-cells-enable-durable-engraftment-of-subcutaneously-transplanted-islets/. Accessed March 26, 2023.

« Back to 2022 American Transplant Congress

Visit Our Partner Sites

American Transplant Congress (ATC)

Visit the official site for the American Transplant Congress »

American Journal of Transplantation

The official publication for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS) »

American Society of Transplantation (AST)

An organization of more than 3000 professionals dedicated to advancing the field of transplantation. »

American Society of Transplant Surgeons (ASTS)

The society represents approximately 1,800 professionals dedicated to excellence in transplantation surgery. »

Copyright © 2013-2023 by American Society of Transplantation and the American Society of Transplant Surgeons. All rights reserved.

Privacy Policy | Terms of Use | Cookie Preferences