Severe pancreatitis is accompanied by a strong fibrotic response characterized through
the presence of activated myofibroblasts. Beside hematopoietic stem cells and resident
fibroblasts, pancreatic stellate cells are traded as the main cell population giving
rise to activated myofibroblasts. The origin of myofibroblasts is highly under debate
and so far not successfully clarified. In vivo evidences that stellate cells are predominantly
responsible for the stromal reaction are still missing. Therefore, we performed lineage-tracing
experiments of pancreatic stellate cells in Wt1CreERT2;LSL-td-Tomato mice and analyzed the fibrotic response after caerulein treatment and
pancreatic duct ligation. Wt1 positive cell identity, localization and quantification
were determined with immunohistochemistry and immunofluorescence staining as well
as FACS analyses. We identified a periacinar stellate cell population which is positive
for Wt1Cre expression. Induction of cerulein-mediated pancreatitis associated with
a fibrotic reaction lead to a slightly elevated number of Wt1 positive cells. However,
Wt1 positive cells represent only a minor cell population of alpha-Sma positive myofibroblasts.
Nevertheless, isolated pancreatic fibroblasts from cerulein-treated mice show an elevated
number of Wt1 positive cells compared to untreated control mice and a strong myofibroblast
activation of Wt1 positive cells is discovered at least under cell culture conditions.
Based on our lineage tracing data, we consider that Wt1-positive pancreatic stellate
cells represent merely a minor source of mesenchymal cells, which are responsible
for the fibrotic reaction in vivo. However, the Wt1 positive stellate cells demonstrate
a high capacity of myofibroblast formation in vitro.
