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

腺体等复杂器官的再生仍然困难。对于器官的再生，最有前景的策略之一是加速自然存在的再生能力。虽然已经报道了几种增强唾液腺再生的方法，但这些基于细胞的治疗到目前为止还不够充分。因此，我们的目标是利用体细胞干细胞研究唾液腺再生的潜力，体细胞干细胞具有向几乎所有唾液腺细胞分化的能力。首先，我们研究了细胞移植对受照射唾液腺的影响。20Gy射线照射后，大鼠颌下腺功能受损。将同种异体骨髓单个核细胞移植到颌下腺。观察唾液腺分泌恢复情况，治疗窗至少在移植后1~14d。另一方面，未观察到从单个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，这种干细胞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，培养的细胞表现出向腺泡和导管的分化。研究了这种发育的可能触发因素，并提出了自分泌或旁分泌机制的可能性。

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.