Division of Gastroenterology, Department of Internal Medicine, University of Rostock, 18057 Rostock, Germany.
Cell Res. 2010 Mar;20(3):288-98. doi: 10.1038/cr.2010.10. Epub 2010 Jan 26.
Origin and fate of pancreatic stellate cells (PSCs) before, during and after pancreatic injury are a matter of debate. The crucial role of PSCs in the pathogenesis of pancreatic fibrosis is generally accepted. However, the turnover of the cells remains obscure. The present study addressed the issue of a potential bone marrow (BM) origin of PSCs. We used a model of stable hematopoietic chimerism by grafting enhanced green fluorescence protein (eGFP)-expressing BM cells after irradiation of acceptor rats. Chimerism was detected by FACS analysis of eGFP-positive cells in the peripheral blood. Dibutyltin dichloride (DBTC) was used to induce acute pancreatic inflammation with subsequent recovery over 4 weeks. Investigations have been focused on isolated cells to detect the resting PSC population. The incidence of eGFP-positive PSC obtained from the pancreas of chimeric rats was approximately 7% in healthy pancreatic tissue and increased significantly to a mean of 18% in the restored pancreas 4 weeks after DBTC-induced acute inflammation. Our results suggest that BM-derived progenitor cells represent a source of renewable stellate cells in the pancreas. Increased numbers of resting PSCs after regeneration point toward enhanced recruitment of BM-derived cells to the pancreas and/or re-acquisition of a quiescent state after inflammation-induced activation.
胰腺星状细胞（PSCs）在胰腺损伤前后的起源和命运一直存在争议。普遍认为 PSCs 在胰腺纤维化发病机制中起着关键作用。然而，细胞的更替仍然不清楚。本研究探讨了 PSCs 潜在的骨髓（BM）起源问题。我们通过辐照接受者大鼠后移植表达增强型绿色荧光蛋白（eGFP）的 BM 细胞，建立了稳定的造血嵌合体模型。通过外周血中 eGFP 阳性细胞的 FACS 分析检测嵌合率。二丁基锡二氯化物（DBTC）用于诱导急性胰腺炎，随后在 4 周内恢复。研究集中在分离的细胞上，以检测静止的 PSC 群体。从嵌合大鼠胰腺中获得的 eGFP 阳性 PSC 的发生率在健康胰腺组织中约为 7%，在 DBTC 诱导的急性炎症后 4 周恢复的胰腺中显著增加至平均 18%。我们的结果表明，BM 源性祖细胞是胰腺中可再生星状细胞的来源。再生后静止 PSC 数量的增加表明 BM 源性细胞向胰腺的募集增加，或在炎症诱导的激活后重新获得静止状态。
