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衰老小鼠受辐照肠隐窝中干细胞再生的改变。

Altered stem cell regeneration in irradiated intestinal crypts of senescent mice.

作者信息

Martin K, Potten C S, Roberts S A, Kirkwood T B

机构信息

Biological Gerontology Group, University of Manchester, Oxford Road, Manchester M13 9PT, UK.

出版信息

J Cell Sci. 1998 Aug;111 ( Pt 16):2297-303. doi: 10.1242/jcs.111.16.2297.

DOI:10.1242/jcs.111.16.2297
PMID:9683625
Abstract

Ageing is associated with a progressive deterioration in the functions of many organs within the body. In tissue with high cell turnover, the maintenance of the stem cells is of particular importance. Any accumulation of damage in stem cells may affect their function and hence threaten the homeostasis and regenerative capacity of the tissue. The small intestine represents a good model for the study of stem cells because of its spatial and hierarchical organisation. We have examined the effect of age on stem cell regenerative capacity after irradiation, using the microcolony assay. Crypt survival levels, the growth rate of surviving crypts, and the number of cells able to repopulate a crypt have been investigated by irradiating groups of 6-7 month old and 28-30 month old ICRFa male mice. After high doses of irradiation, the surviving crypts in old mice were both smaller and fewer in number than in young mice. The growth rate of surviving crypts was determined by measuring the crypt area and the number of cells/crypt at various times after 14 Gy irradiation. There was a growth delay of between about one half and one day in the older mice. Surprisingly, the number of clonogenic cells per crypt was estimated to be greater in the older mice. These studies indicate important age-related alterations in the capacity to regenerate the crypts after radiation damage.

摘要

衰老与体内许多器官功能的逐渐衰退有关。在细胞更新率高的组织中,干细胞的维持尤为重要。干细胞中任何损伤的积累都可能影响其功能,进而威胁组织的稳态和再生能力。由于小肠具有空间和层次结构,它是研究干细胞的一个良好模型。我们使用微集落测定法研究了年龄对辐射后干细胞再生能力的影响。通过对6 - 7月龄和28 - 30月龄的ICRFa雄性小鼠组进行辐射,研究了隐窝存活水平、存活隐窝的生长速率以及能够重新填充一个隐窝的细胞数量。高剂量辐射后,老年小鼠中存活的隐窝比年轻小鼠中的更小且数量更少。通过测量14 Gy辐射后不同时间的隐窝面积和每个隐窝的细胞数量来确定存活隐窝的生长速率。老年小鼠的生长延迟约为半天到一天。令人惊讶的是,估计老年小鼠每个隐窝中克隆形成细胞的数量更多。这些研究表明,辐射损伤后隐窝再生能力存在与年龄相关的重要改变。

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