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

Abstract

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. (Transplantation 2023;107: e98-e108).K.V. participated in study design, writing of the article, performance of the research, and data analysis. N.C.-G., R.P., and N.D. participated in study design, performance of the research, and article editing. P.A. participated in study design and performance of the research. B.A.M.-G. participated in data analysis and article editing. I.J. participated in study design and article editing. D.O. and T.K. participated with supply of materials and article editing. A.H. and L.J.W. participated with study design, reagents, and article editing. A.M.J.S. participated with study design, reagents and analytical tools, data analysis, and article editing.

Is ABO Compatibility Important in Islet Transplantation?

“…It is therefore somewhat surprising that ABH expression in islet preparations before and after transplant has not been characterized until now. In this issue of Transplantation , Verhoeff et al 3 present a detailed immunohistochemical and flow cytometric survey of ABH antigen levels in human pancreatic tissue, isolated human clinical-grade islets, and islets derived from human embryonic stem cells (hESCs). After confirming that ABH antigens are present on acinar cells but not on endocrine and ductal cells in the pancreas, the authors demonstrate that islet preparations consist primarily of ABH-negative endocrine cells but are significantly contaminated with ABH-positive acinar cells.…”