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REGENERATION OF SALIVARY GLAND USING TISSUE ENGINEERING AND GROWTH FACTORS

利用组织工程和生长因子实现唾液腺再生

基本信息

批准号：
16390584
负责人：
KAGAMI Hideaki
金额：
$ 8.32万
依托单位：
The University of Tokyo (2006)Nagoya University (2004-2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390584/
关键词：
salivary gland regeneration cell culture tissue engineering gene analysis DNA microarray cell therapy differential display ディファレンシャルディスプレイ

项目摘要

Salivary gland atrophy is a serious clinical problem for elderly and patients who undergo irradiation. However, regeneration of salivary gland is not feasible. In this project, we have investigated the genes potentially relating to the regeneration of salivary gland. Furthermore, a possibility of cell therapy on atrophic salivary gland was investigated. Male Wistar rats (nine weeks old) were anesthetized and the unilateral duct of submandibular gland was ligated. After ductal ligation, salivary gland immediately becomes atrophic. The gland regenerates after the ligation removal. The ligation was removed after one week and the gland was harvested at 12 hours, 36 hours, and 6 days after removal of ligation. The results from DNA microarray analyses showed immediate increase of clusterin expression after removal of ligation, which returned to almost basal level after 6 days. The gene and protein expression of clusterin was confirmed by RT-PCR and immunohistochemistry, respectively. In the normal gland, clusterin was equally distributed but limited in the cytosol of most of the parenchyma. After ductal ligation and removal, clusterin immediately accumulated intra-luminal space and strong expression was continuously observed along with the luminal surface of the atrophic acini until day 3. The expression was decreased after day 6 and the distribution returned to that of the normal gland. The results from this study demonstrated the dynamic change of this protein during regeneration process of rat submandibular gland, though the possible roles yet to be known. Next, we have generated a mouse model of salivary hypofunction by irradiation. Monocytes from bone marrow were harvested by centrifugation and transplanted to the atrophic submanidbular gland. In this study, various factors which affect the attachment and survival of transplanted cells were investigated. Furthermore, functional recovery of the atrophic salivary gland was also evaluated.

唾液腺萎缩对于老年人和接受放射治疗的患者来说是一个严重的临床问题。然而，唾液腺的再生是不可行的。在这个项目中，我们研究了可能与唾液腺再生相关的基因。此外，还研究了细胞治疗萎缩唾液腺的可能性。将雄性Wistar大鼠(9周龄)麻醉并结扎单侧颌下腺导管。导管结扎后，唾液腺立即萎缩。结扎去除后腺体会再生。一周后除去结扎，并在除去结扎后12小时、36小时和6天收获腺体。 DNA微阵列分析的结果显示，在去除连接后，簇蛋白表达立即增加，6天后几乎恢复到基础水平。分别通过RT-PCR和免疫组化证实clusterin的基因和蛋白表达。在正常腺体中，簇蛋白均匀分布，但仅限于大部分实质的细胞质中。导管结扎并去除后，clusterin立即在管腔内积聚，并沿着萎缩腺泡的管腔表面持续观察到强表达，直到第3天。第6天后表达减少，分布恢复到正常腺体的分布。本研究结果证明了该蛋白在大鼠颌下腺再生过程中的动态变化，但其可能的作用尚不清楚。接下来，我们通过照射建立了唾液腺功能减退的小鼠模型。通过离心收获骨髓中的单核细胞并将其移植到萎缩的颌下腺。在这项研究中，研究了影响移植细胞附着和存活的各种因素。此外，还评估了萎缩唾液腺的功能恢复。