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Investigation on the mechanisms of salivary gland tissue regeneration and effect of somatic stem cell transplantation

唾液腺组织再生机制及成体干细胞移植效果的研究

基本信息

批准号：
19390512
负责人：
KAGAMI Hideaki
金额：
$ 12.15万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

项目摘要

The regeneration of complex organ such as gland is still difficult. For the regeneration of organ, one of the most promising strategies is the acceleration of naturally existing regeneration capability. Although several approaches to enhance salivary gland regeneration have been reported, those cell based therapy are not sufficient so far. Accordingly, it was our aim to investigate a potential of salivary gland regeneration by use of somatic stem cells, which posses differentiating capability to virtually all salivary gland cells. First, we have investigated the effect of cell transplantation to irradiated salivary gland. Rat submandibular gland function was damaged after 20Gy irradiation. Allogenic mononuclear cells from bone marrow were transplanted to submandibular gland. The recovery of salivary gland secretion was observed and the treatment window was at least 1-14 days after transplantation. On the other hand, differentiation from mononuclear cells to parenchymal cells was not observed. Second, we have investigated the potential of stem cell culture from salivary gland, which can differentiate into all components of salivary gland. In this culture, possible salivary gland stem cells can be retained for relatively longer period and the cultured cells showed differentiation into acinar and duct. The possible trigger for the development has been investigated and the potential of autocrine or paracrine mechanisms were suggested.

腺体等复杂器官的再生仍然很困难。对于器官的再生，最有前途的策略之一是加速自然存在的再生能力。尽管已经报道了几种增强唾液腺再生的方法，但迄今为止这些基于细胞的疗法还不够。因此，我们的目标是研究通过使用成体干细胞进行唾液腺再生的潜力，该干细胞对几乎所有唾液腺细胞具有分化能力。首先，我们研究了细胞移植对辐照唾液腺的影响。 20Gy照射后大鼠颌下腺功能受损。来自骨髓的同种异体单核细胞被移植到颌下腺。观察唾液腺分泌的恢复情况，治疗窗口至少为移植后1-14天。另一方面，没有观察到从单核细胞向实质细胞的分化。其次，我们研究了唾液腺干细胞培养的潜力，它可以分化为唾液腺的所有成分。在这种培养中，可能的唾液腺干细胞可以保留相对较长的时间，并且培养的细胞表现出向腺泡和导管的分化。已经研究了该发展的可能触发因素，并提出了自分泌或旁分泌机制的潜力。