Preexisting pancreatic to acinar cell, but not islet β cell, regeneration
Preexisting pancreatic to acinar cell, but not islet β cell, regeneration
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DOI：
10.1172/jci29988
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发表时间：
2007-04-01
影响因子：
15.9
通讯作者：
Stoffers, Doris A.
中科院分区：
文献类型：
--
作者：
Desai, Biva M.;Oliver-Krasinski, Jennifer;Stoffers, Doris A.
有人提出，胰腺腺泡细胞可以作为胰岛的祖细胞，这一概念对于增加糖尿病患者产生胰岛素的β细胞量的治疗努力具有重大意义。我们报告了我们认为是第一个体内谱系追踪方法来确定胰腺腺泡细胞的可塑性潜力。我们开发了一种腺泡细胞特异性诱导型 Cre 重组酶转基因小鼠，当与报告菌株交配并用他莫昔芬脉冲时，会导致腺泡细胞及其后代的永久和特异性标记。在不同时间段的观察和使用多种模型引发损伤期间，我们未能观察到标记细胞进入内分泌室的任何追逐，这表明腺泡细胞在成年小鼠体内通常不会转分化为胰岛β细胞。相反，我们观察到先前存在的腺泡细胞的复制在部分胰腺切除术后新腺泡细胞的再生中发挥着重要作用。这些结果表明成熟的腺泡细胞具有兼性腺泡但不具有内分泌祖细胞能力。
It has been suggested that pancreatic acinar cells can serve as progenitors for pancreatic islets, a concept with substantial implications for therapeutic efforts to increase insulin-producing beta cell mass in patients with diabetes. We report what we believe to be the first in vivo lineage tracing approach to determine the plasticity potential of pancreatic acinar cells. We developed an acinar cell-specific inducible Cre recombinase transgenic mouse, which, when mated with a reporter strain and pulsed with tamoxifen, resulted in permanent and specific labeling of acinar cells and their progeny. During various time periods of observation and using several models to provoke injury, we failed to observe any chase of the labeled cells into the endocrine compartment, indicating that acinar cells do not normally transdifferentiate into islet beta cells in vivo in adult mice. In contrast, we observed a substantial role for replication of preexisting acinar cells in the regeneration of new acinar cells after partial pancreatectomy. These results indicate that mature acinar cells harbor a facultative acinar but not endocrine progenitor capacity.