Zafar, Ali, Lee, Jou, Yesmin, Shameema, Paget, Michelle B., Bailey, Clifford J., Murray, Hilary E. and Downing, Richard (2019). Rotational culture and integration with amniotic stem cells reduce porcine islet immunoreactivity in vitro and slow xeno‐rejection in a murine model of islet transplantation. Xenotransplantation, 26 (4),
Abstract
Background: Pre-transplant modification of porcine islets may improve their suitability for clinical use in diabetes management by supporting graft function and reducing the potential for xeno-rejection. The present study investigates intra-graft incorporation of stem cells that secrete beta (β)-cell trophic and immunomodulatory factors to preserve function and alter immune cell responsiveness to porcine islets. Methods: Isolated porcine islets were maintained in a three-dimensional rotational cell culture system (RCCS) to facilitate aggregation with human amniotic epithelial cells (AECs). Assembled islet constructs were assessed for functional integrity and ability to avoid xeno-recognition by CD4+ T-cells using mixed islet:lymphocyte reaction assays. To determine whether stem cell-mediated modification of porcine islets provided a survival advantage over native islets, structural integrity was examined in a pig-to-mouse islet transplant model. Results: Rotational cell culture system supported the formation of porcine islet:AEC aggregates with improved insulin-secretory capacity compared to unmodified islets, whilst the xeno-response of purified CD4+ T-cells to AEC-bearing grafts was significantly (P < 0.05) attenuated. Transplanted AEC-bearing grafts demonstrated slower rejection in immune-competent recipients compared to unmodified islets. Conclusions/interpretation: Rotational culture enables pre-transplant modification of porcine islets by integration with immunomodulatory stem cells capable of subduing xeno-reactivity to CD4+ T-cells. This reduces islet rejection and offers translational potential to widen availability and improve the clinical effectiveness of islet transplantation.
Publication DOI: | https://doi.org/10.1111/xen.12508 |
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Divisions: | College of Health & Life Sciences > School of Biosciences College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research College of Health & Life Sciences College of Health & Life Sciences > Chronic and Communicable Conditions |
Additional Information: | This is the peer reviewed version of the following article: Zafar, A, Lee, J, Yesmin, S, et al. Rotational culture and integration with amniotic stem cells reduce porcine islet immunoreactivity in vitro and slow xeno‐rejection in a murine model of islet transplantation. Xenotransplantation. 2019;e12508, which has been published in final form at https://doi.org/10.1111/xen.12508. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving. |
Uncontrolled Keywords: | T-cell,amniotic epithelial cells,immunomodulation,porcine islets,rotational cell culture,xenotransplantation,Immunology,Transplantation |
Publication ISSN: | 1399-3089 |
Last Modified: | 06 Aug 2024 08:22 |
Date Deposited: | 16 Apr 2019 14:43 |
Full Text Link: | |
Related URLs: |
https://onlinel ... .1111/xen.12508
(Publisher URL) http://www.scop ... tnerID=8YFLogxK (Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2019-07-01 |
Published Online Date: | 2019-04-08 |
Accepted Date: | 2019-03-07 |
Authors: |
Zafar, Ali
Lee, Jou Yesmin, Shameema Paget, Michelle B. Bailey, Clifford J. ( ![]() Murray, Hilary E. Downing, Richard |