Formation of Pancreatic β-cells from Precursor Cells Contributes to the Reversal of Established Type 1 Diabetes

Overview

Journal Cell Immunol

Publisher Elsevier

Specialties Allergy & Immunology
Cell Biology

Date 2021 Apr 18

PMID 33866285

Authors

Tobechukwu K Ukah

Alexis N Cattin-Roy

George E Davis

Habib Zaghouani

Affiliations

Soon will be listed here.

Abstract

Ig-GAD2, an antigen-specific immune modulator, requires bone marrow (BM) cell transfer in order to restore beta (β)-cell formation and induce recovery from established type 1 diabetes (T1D). The BM cells provide endothelial precursor cells (EPCs) that give rise to islet resident endothelial cells (ECs). This study shows that, during development of T1D, the immune attack causes collateral damage to the islet vascular network. The EPC-derived ECs repair and restore islet blood vessel integrity. In addition, β-cell genetic tracing indicates that the newly formed β-cells originate from residual β-cells that escaped the immune attack and, unexpectedly, from β-cell precursors. This indicates that the rejuvenated islet microenvironment invigorates formation of new β-cells not only from residual β-cells but also from precursor cells. This is twofold significant from the perspective of precursor cells as a safe reserve for restoration of β-cell mass and its promise for therapy of T1D long after diagnosis.

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