Correlation of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes in Total Pancreatectomy With Islet Autotransplantation

Authors

Jayachandra Kuncha
Carly M Darden
Yang Liu
Michael Lawrence
J Sebastian Danobeitia
Bashoo Naziruddin

Language

English

Publication Date

1-1-2025

Journal

Cell Transplantation

DOI

10.1177/09636897251317048

PMID

39994886

PMCID

PMC11863243

PubMedCentral® Posted Date

2-24-2025

PubMedCentral® Full Text Version

Post-print

Abstract

This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including alcoholic, hereditary, idiopathic, Oddi dysfunction, and pancreatic divisum compared to healthy controls. The overall expression of LAMA5 positively correlated with expression of the ECM proteins pan-laminin (R = 0.63, P < 0.001), collagen IV (R = 0.67, P < 0.001), and Perlecan (R = 0.71, P < 0.001). Increased LAMA5 expression was observed within islet endothelial vascular tissue and the peri-islet basal membrane. Increased LAMA5 expression in the pancreas correlated with poor islet isolation yield and posttransplant islet function after 3 months. Increased endothelial expression of LAMA5 and ECM proteins is indicative of progressive damage to the pancreas and correlates with poor graft function after TPIAT.

Keywords

Retrospective Studies, Humans, Male, Female, Adult, Middle Aged, Pancreatectomy, Islets of Langerhans Transplantation, Transplantation, Autologous, Laminin, Pancreatitis, Chronic, Pancreas, Extracellular Matrix Proteins, Treatment Outcome, chronic pancreatitis, laminin alpha 5, extracellular matrix proteins, islets, inflammation

Published Open-Access

yes

Recommended Citation

Kuncha, Jayachandra; Darden, Carly M; Liu, Yang; et al., "Correlation of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes in Total Pancreatectomy With Islet Autotransplantation" (2025). Faculty, Staff and Student Publications. 6185.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6185