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

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:107

Enthalten in:

Transplantation - 107(2023), 4 vom: 01. Apr., Seite e98-e108

Sprache:

Englisch

Beteiligte Personen:

Verhoeff, Kevin [VerfasserIn]
Cuesta-Gomez, Nerea [VerfasserIn]
Albers, Patrick [VerfasserIn]
Pawlick, Rena [VerfasserIn]
Marfil-Garza, Braulio A [VerfasserIn]
Jasra, Ila [VerfasserIn]
Dadheech, Nidheesh [VerfasserIn]
O'Gorman, Doug [VerfasserIn]
Kin, Tatsuya [VerfasserIn]
Halpin, Anne [VerfasserIn]
West, Lori J [VerfasserIn]
Shapiro, A M James [VerfasserIn]

Links:

Volltext

Themen:

ABO Blood-Group System
Antigens
Journal Article

Anmerkungen:

Date Completed 05.04.2023

Date Revised 23.05.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1097/TP.0000000000004347

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM347434037