M2 macrophages play an important role in tissue repair and regeneration. They have also been found to modulate beta cell replication in mouse models of pancreatic injury and disease. We have previously reported that beta cell replication is strongly increased in a subgroup of human organ donors characterized by prolonged duration of stay in an intensive care unit (ICU) and increased number of leucocytes in the pancreatic tissue. In the present study we investigated the relationship between duration of stay in ICU, M2 macrophages, vascularization and pancreatic cell replication. Pancreatic organs from 50 non-diabetic donors with different duration of stay in ICU were analyzed by immunostaining and digital image analysis. The number of CD68+CD206+ M2 macrophages increased 3- to 6-fold from ≥6 days duration of stay in ICU onwards. This was accompanied by a 3-fold increased vascular density and a 4- to 9-fold increase in pancreatic cells positive for the replication marker Ki67. A strong correlation was observed between the number of M2 macrophages and beta cell replication. These results show that prolonged duration of stay in ICU is associated with an increased M2 macrophage number, increased vascular density and an overall increase in replication of all pancreatic cell types. Our data show evidence of marked levels of tissue repair in the human donor pancreas.
Original languageEnglish
Pages (from-to)401-412
Number of pages12
JournalDiabetes
Volume69
Issue number3
Publication statusPublished - Mar 2020

ID: 49105083