Tags

Type your tag names separated by a space and hit enter

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; 26(4):e12508X

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.

Authors+Show Affiliations

The Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.The Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.The Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.The Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.Diabetes Research, School of Life and Health Sciences, Aston University, Birmingham, UK.The Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.The Islet Research Laboratory, Worcestershire Clinical Research Unit, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30963627

Citation

Zafar, Ali, 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, vol. 26, no. 4, 2019, pp. e12508.
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;26(4):e12508.
Zafar, A., Lee, J., Yesmin, S., Paget, M. B., Bailey, C. J., Murray, H. E., & Downing, R. (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), pp. e12508. doi:10.1111/xen.12508.
Zafar A, 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;26(4):e12508. PubMed PMID: 30963627.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Zafar,Ali, AU - Lee,Jou, AU - Yesmin,Shameema, AU - Paget,Michelle B, AU - Bailey,Clifford J, AU - Murray,Hilary E, AU - Downing,Richard, Y1 - 2019/04/08/ PY - 2018/09/12/received PY - 2019/02/04/revised PY - 2019/03/07/accepted PY - 2019/4/10/pubmed PY - 2019/4/10/medline PY - 2019/4/10/entrez KW - T-cell KW - amniotic epithelial cells KW - immunomodulation KW - porcine islets KW - rotational cell culture KW - xenotransplantation SP - e12508 EP - e12508 JF - Xenotransplantation JO - Xenotransplantation VL - 26 IS - 4 N2 - 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. SN - 1399-3089 UR - https://www.unboundmedicine.com/medline/citation/30963627/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 L2 - https://doi.org/10.1111/xen.12508 DB - PRIME DP - Unbound Medicine ER -