DCAMKL-1: a new horizon for pancreatic progenitor identification.
DCAMKL-1: a new horizon for pancreatic progenitor identification.
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DCAMKL-1：胰腺祖细胞鉴定的新视野。
DOI：
10.1152/ajpgi.00259.2010
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
Srinivasan,Shanthi
中科院分区：
文献类型：
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作者：
Mwangi,SimonM;Srinivasan,Shanthi
1型糖尿病是产生胰岛素的胰腺β细胞自身免疫破坏的结果。虽然胰岛移植在治疗1型糖尿病患者的高血糖方面显示出巨大的潜力，但供体胰岛的可用性仍然是一个主要的障碍。由于缺乏合适的标记物用于鉴定，旨在通过分化成人胰腺干细胞/前体细胞来产生功能性胰岛素分泌细胞的细胞替代策略一直受到阻碍。胰腺前体细胞在β细胞的再生和胰腺癌的发生发展中起着重要的作用。β-细胞质量在一生中经历代偿性变化，特别是在需求增加和受伤期间。这表明成人胰腺中存在干细胞/祖细胞或其他β细胞更新机制。在成人胰腺中缺乏可证明的胚胎β细胞前体的标记，加上遗传谱系追踪研究的结果表明，β细胞主要是在生理条件下和胰腺损伤后在成年小鼠中通过自我复制先前存在的β细胞而产生的(2，6)，这让人怀疑出生后胰腺中是否存在干细胞/祖细胞(1)。然而，最近的几项研究表明，在成年小鼠胰腺的导管上皮细胞中不仅存在内分泌和外分泌谱系细胞的祖细胞(5)，而且在小鼠胰腺损伤后看到的一些新的β-细胞来自表达基本螺旋-环-螺旋转录因子Neurgenin3的前体细胞(11)。
TYPE 1 DIABETES RESULTS FROM the autoimmune destruction of insulin-producing pancreatic β-cells. Although islet transplantation has shown great potential in the treatment of hyperglycemia in type 1 diabetes patients, availability of donor islets remains a major obstacle (4). Cell replacement strategies aimed at generating functional insulin-producing cells through differentiation of adult pancreatic stem cells/progenitors have been hindered by a lack of suitable markers for their identification.Pancreatic progenitor cells are important in the regeneration of β-cells and in the development of pancreatic cancer. β-Cell mass undergoes compensatory changes throughout life, particularly during times of increased demand and during injury. This suggests the presence of stem cells/progenitors or some other mechanism of β-cell renewal in the adult pancreas. The lack of demonstrable markers of embryonic β-cell progenitors in the adult pancreas coupled with results from genetic lineage tracing studies showing that β-cells were largely generated by self-replication of preexisting β-cells in adult mice both under physiological conditions and following pancreatic injury (2, 6) cast doubt on the existence of stem cells/progenitors in the pancreas after birth (1). However, several recent studies have demonstrated not only the existence of progenitors in the ductal epithelium for both endocrine and exocrine lineage cells in the adult mouse pancreas (5), but also that some of the new β-cells seen following pancreatic injury in mice arise from progenitors expressing the basic helix-loop-helix transcription factor neurogenin3 (11).