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Applying the regenerative medicine to cure the side-effects causing by the chemo/radiation therapy such as oral mucositis

应用再生医学治疗化疗/放射治疗引起的口腔粘膜炎等副作用

基本信息

批准号：
23659921
负责人：
OKUMURA Teruhito
金额：
$ 2.33万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2011
资助国家：
日本
起止时间：
2011 至 2012
项目状态：
已结题

项目摘要

Oral mucositis is a serious and painful side effect for patients with head and neck cancer who received radiation- and/or chemo-therapy. It causes not only the limitation on the ability of patients to tolerate cancer therapies in some cases but also the harmful effects on the quality of life. However, current clinical strategies cannot efficiently prevent the occurrence of oral mucositis. Therefore, effectivetherapy should be developed urgently. BMDCs isolated from male C3H mice were transplanted to the female mice just after the irradiation through the tail vein. After 2, 5, 7 and 11 days of irradiation, the tongues were harvested, and the macroscopic, histological and immunological analyses were performed to clarify the effects of BMDC transplantation. After 2 days of irradiation, the tongues of non-treated mice (IR) showed significant apoptosis of the cells throughout the basal cell layer while few cells were observed in that of BMDCs-treated mice (BM). After 7 days of irradiation, while the ulcer area became maximum in the tongues of IR, the area of ulcers formed in BM specimens was approximately 60% of IR and preserved the epithelial thickness. Consistent with this appearance, histological analysis shows that tongues of BM demonstrated an increased level of tissue regenerative activity such as blood vessel formation and cell proliferation. Finally, after 11 days of irradiation, the area of ulcers in BM decreased remarkably compared with that in IR. Our data suggests that cell therapy with BMDCs can prevent the maximum ulceration caused by head and neck irradiation.

口腔粘膜炎是头颈部癌症患者接受放疗和/或化疗后的一种严重而痛苦的副作用。在某些情况下，它不仅限制了患者耐受癌症治疗的能力，而且对生活质量产生有害影响。然而，目前的临床策略不能有效地预防口腔粘膜炎的发生。因此，迫切需要开发有效的治疗方法。从雄性C3 H小鼠分离的BMDCs在照射后立即通过尾静脉移植到雌性小鼠。分别于照射后2、5、7、11 d取舌，进行大体、组织学和免疫学分析，以明确BMDC移植的效果。照射2天后，未处理小鼠（IR）的舌头显示出整个基底细胞层的细胞凋亡，而BMDC处理小鼠（BM）的舌头中观察到很少的细胞。照射7天后，虽然溃疡面积成为最大的舌头IR，BM标本中形成的溃疡面积约为60%的IR和保存上皮厚度。与这种外观一致，组织学分析表明，BM的舌表现出组织再生活性水平的增加，如血管形成和细胞增殖。最后，照射11天后，BM的溃疡面积显着减少相比，在IR。我们的数据表明，细胞治疗与BMDCs可以防止头部和颈部照射引起的最大溃疡。