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): e12508, 2019 07.
Article
em En
| MEDLINE
| ID: mdl-30963627
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 (ß)-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 isletlymphocyte 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 isletAEC 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante das Ilhotas Pancreáticas
/
Ilhotas Pancreáticas
/
Técnicas de Cultura de Células
/
Células Epiteliais
/
Células Secretoras de Insulina
/
Xenoenxertos
/
Rejeição de Enxerto
/
Âmnio
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article