A 2ND PATHWAY FOR REGENERATION OF ADULT EXOCRINE AND ENDOCRINE PANCREAS - A POSSIBLE RECAPITULATION OF EMBRYONIC-DEVELOPMENT

A 2ND PATHWAY FOR REGENERATION OF ADULT EXOCRINE AND ENDOCRINE PANCREAS - A POSSIBLE RECAPITULATION OF EMBRYONIC-DEVELOPMENT
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DOI:
10.2337/diabetes.42.12.1715
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发表时间:
1993-12-01
期刊:
影响因子:
7.7
通讯作者:
SMITH, FE
SMITH, FE
中科院分区:
医学1区
文献类型:
--
作者:
BONNERWEIR, S;BAXTER, LA;SMITH, FE

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在年轻成年大鼠进行90%的部分胰腺切除术后,内分泌胰腺和外分泌胰腺都发生了实质性的再生。我们以前报道过,先前存在的胰岛和外分泌细胞的复制增强了3- 4倍。在这里,我们报告了再生的第二途径,即导管上皮中前体细胞的增殖和分化。用5-溴-2'-脱氧尿苷进行体内脉冲标记显示,导管上皮发生扩张。增生首先见于胰总管,随着小管增生的病灶区域形成,依次在胰管树的小管中出现。胰腺切除术后60小时,只有这些病灶区域显示重的5-溴-2;脱氧尿苷染色。在胰腺切除术后3天,这些增生性小管占胰腺体积的21.8%,但在胰腺切除术后7天并不常见。与这些区域的出现和消失相一致的是,胰腺残体的生长速度比同等的假动物增加了3.5倍。这些小管分化成新的胰岛和外分泌组织,形成新的胰腺小叶,与先前存在的小叶无法区分。这种快速再生的第二种途径概括了其导管增殖和随后分化的胚胎发育模式。此外,这些研究提供了成人胰腺中存在前体细胞/干细胞的证据。
Substantial regeneration of both the endocrine and exocrine pancreas occurs after a 90% partial pancreatectomy in the young adult rat. We have reported previously that replication of preexisting islet and exocrine cells is enhanced 3- to 4-fold. Here, we report a second pathway of regeneration, that of proliferation and differentiation of precursor cells in the ductal epithelium. As shown with in vivo pulse labeling using 5-bromo-2'-deoxyuridine, an expansion of the ductal epithelium occurs. Proliferation is seen first in the common pancreatic duct and sequentially in smaller ducts of the ductal tree as focal areas of proliferating small ductules form. By 60 h after pancreatectomy, only these focal areas show heavy 5-bromo-2;-deoxyuridine staining. These proliferating ductules comprise 21.8% of the pancreatic volume at 3 days after pancreatectomy but are uncommon at 7 days after pancreatectomy. Coincident with the appearance and disappearance of these regions was a 3.5-fold increased growth of the pancreatic remnant compared with its equivalent of sham animals. These small ductules differentiate into new pancreatic islets and exocrine tissue, forming new lobules of pancreas that are indistinguishable from the preexisting ones. This second pathway of rapid regeneration recapitulates embryonic development in its pattern of ductal proliferation subsequent differentiation. Furthermore, these studies provide evidence of the presence of precursor/stem cells in the adult pancreas.