Evaluating the Potential for ABO-incompatible Islet Transplantation: Expression of ABH Antigens on Human Pancreata, Isolated Islets, and Embryonic Stem Cell-derived Islets.

Background: ABO-incompatible transplantation has improved accessibility of kidney, heart, and liver transplantation. Pancreatic islet transplantation continues to be ABO-matched, yet ABH antigen expression within isolated human islets or novel human embryonic stem cell (hESC)-derived islets remain uncharacterized.
Methods: We evaluated ABH glycans within human pancreata, isolated islets, hESC-derived pancreatic progenitors, and the ensuing in vivo mature islets following kidney subcapsular transplantation in rats. Analyses include fluorescence immunohistochemistry and single-cell analysis using flow cytometry.
Results: Within the pancreas, endocrine and ductal cells do not express ABH antigens. Conversely, pancreatic acinar tissues strongly express these antigens. Acinar tissues are present in a substantial portion of cells within islet preparations obtained for clinical transplantation. The hESC-derived pancreatic progenitors and their ensuing in vivo-matured islet-like clusters do not express ABH antigens.
Conclusions: Clinical pancreatic islet transplantation should remain ABO-matched because of contaminant acinar tissue within islet preparations that express ABH glycans. Alternatively, hESC-derived pancreatic progenitors and the resulting in vivo-matured hESC-derived islets do not express ABH antigens. These findings introduce the potential for ABO-incompatible cell replacement treatment and offer evidence to support scalability of hESC-derived cell therapies in type 1 diabetes.
Competing Interests: A.M.J.S. is supported through a Canada Research Chair (Tier 1) in Regenerative Medicine and Transplant Surgery, and through grant support from the Juvenile Diabetes Research Foundation, Diabetes Canada, the Canadian Donation and Transplant Research Program, the Diabetes Research Institute Foundation of Canada, the Alberta Diabetes Foundation, and the Canadian Stem Cell Network. B.A.M.-G. is supported by the Patronato del Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ), the Fundacion para la Salud y la Educacion Dr. Salvador Zubirán (FunSaEd), and the CHRISTUS Excellence and Innovation Center. A.M.J.S. serves as a consultant to ViaCyte Inc. The other authors declare no conflicts of interest.
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