JCI：一种胰腺细胞能够被诱导转化成产胰岛素小岛细胞
在过去的10年里，用新的产胰岛素细胞来替换掉出错或损失掉的细胞一直是糖尿病研究的一个重点课题。之前的组织培养研究显示，一种类型的胰腺细胞能够被诱导转化成产胰岛素小岛细胞。
现在，来自宾夕法尼亚州大学医学院的研究人员证实，这些胰腺细胞不能在动物模型中变成产胰岛素细胞。但是，他们发现受伤的胰腺细胞很容易重生为健康的胰腺细胞——这对治疗胰腺癌和炎症具有重要意义。这项研究的结果发表在4月的《临床检查杂志》（Journal of Clinical Investigation）上。该研究有潜力导致胰腺细胞操作新技术的诞生。
胰腺由两种具有不同功能的部件组成：产胰岛素β细胞构成的小岛和由管细胞和腺细胞构成的较大的外分泌部分。外分泌部分能产生酶并将其传递到负责消化的肠道。糖尿病的病因是β细胞不能正常产生胰岛素，而胰腺癌则常起源于外分泌部分。在特定情况下，组织培养的腺细胞也能合成胰岛素。
最新发现对改变糖尿病研究的重点具有深远意义。此前，Doris Stoffers博士率领的这个研究组和其他研究组的研究结果都显示，β细胞本身是产生新β细胞最有前途的资源。研究的重点目前逐渐转移到直接刺激活体动物中小岛细胞的生长。相比之下，一旦腺细胞被移除生物体外并进行培养，它们则更可能变成其他细胞类型，其中就包括β细胞。因此，Stoffers的动物模型和技术方法目前正被美国、欧洲和中国的研究者用于确定腺细胞能够转化成导管细胞和β细胞的条件。
宾州的这个研究组用一种能永久地、选择性地只标记胰腺细胞的特殊标志物加工小鼠模型。然后，利用化学试剂或手术损伤小鼠的胰腺。胰腺自己愈合或再生，并且特定的胰腺细胞标志物可以通过显微镜来检测。分析结果清晰地显示，腺细胞和小岛在活体动物中的再生过程仍然是分开的。
部分英文原文：
J. Clin. Invest. 117:971-977 (2007). doi:10.1172/JCI29988.
Copyright ©2007 by the American Society for Clinical Investigation
Research Article
Preexisting pancreatic acinar cells contribute to acinar cell, but not islet ß cell, regeneration
Biva M. Desai1, Jennifer Oliver-Krasinski1, Diva D. De Leon1,2, Cyrus Farzad1, Nankang Hong1, Steven D. Leach3 and Doris A. Stoffers1
1Division of Endocrinology, Diabetes, and Metabolism and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 2Division of Pediatric Endocrinology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 3Departments of Surgery and Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Address correspondence to: Doris A. Stoffers, Clinical Research Building, 611B, Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-4399, USA. Phone: (215) 573-5413; Fax: (215) 898-5408; E-mail: stoffers@mail.med.upenn.edu .
Received for publication August 8, 2006, and accepted in revised form January 10, 2007.
Abstract
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 ß 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 ß 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.
英文全文链接：http://www.jci.org/cgi/content/full/117/4/971?
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