Choi Eun Wha, Shin Il Seob, Park So Young, Yoon Eun Ji, Kang Sung Keun, Ra Jeong Chan, Hong Sung Hwa
Laboratory Animal Research Center, Samsung Biomedical Research Institute, Gangnam-gu, Seoul, Republic of Korea.
Cell Transplant. 2014;23(7):873-87. doi: 10.3727/096368913X664586. Epub 2013 Mar 5.
Previously, we found that the intravenous administration of human adipose tissue-derived mesenchymal stem cells was a promising therapeutic option for autoimmune thyroiditis even when the cells were transplanted into a xenogeneic model without an immunosuppressant. Therefore, we explored the comparison between the therapeutic effects of syngeneic and allogeneic adipose tissue-derived stem cells on an experimental autoimmune thyroiditis mouse model. Experimental autoimmune thyroiditis was induced in C57BL/6 mice by immunization with porcine thyroglobulin. Adipose tissue-derived stem cells derived from C57BL/6 mice (syngeneic) or BALB/c mice (allogeneic) or saline as a vehicle control were administered intravenously four times weekly. Blood and tissue samples were collected 1 week after the last transplantation. Adipose tissue-derived stem cells from mice were able to differentiate into multiple lineages in vitro; however, mouse adipose tissue-derived stem cells did not have immunophenotypes identical to those from humans. Syngeneic and allogeneic administrations of adipose tissue-derived stem cells reduced thyroglobulin autoantibodies and the inflammatory immune response, protected against lymphocyte infiltration into the thyroid, and restored the Th1/Th2 balance without any adverse effects. However, different humoral immune responses were observed for infused cells from different stem cell sources. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic and syngeneic administration, in that order. The stem cells were mostly found in the spleen, not the thyroid. This migration might be because the stem cells primarily function in systemic immune modulation, due to being given prior to disease induction. In this study, we confirmed that there were equal effects of adipose tissue-derived stem cells in treating autoimmune thyroiditis between syngeneic and allogeneic transplantations.
此前，我们发现静脉注射人脂肪组织来源的间充质干细胞是自身免疫性甲状腺炎一种有前景的治疗选择，即便在没有免疫抑制剂的情况下将这些细胞移植到异种模型中也是如此。因此，我们探究了同基因和异基因脂肪组织来源的干细胞对实验性自身免疫性甲状腺炎小鼠模型治疗效果的比较。通过用猪甲状腺球蛋白免疫，在C57BL/6小鼠中诱导实验性自身免疫性甲状腺炎。每周静脉注射4次来自C57BL/6小鼠（同基因）或BALB/c小鼠（异基因）的脂肪组织来源的干细胞或作为载体对照的生理盐水。在最后一次移植后1周收集血液和组织样本。小鼠脂肪组织来源的干细胞在体外能够分化为多个谱系；然而，小鼠脂肪组织来源的干细胞不具有与人类相同的免疫表型。同基因和异基因脂肪组织来源的干细胞给药均降低了甲状腺球蛋白自身抗体和炎症免疫反应，防止淋巴细胞浸润甲状腺，并恢复了Th1/Th2平衡，且无任何不良反应。然而，对于来自不同干细胞来源的注入细胞，观察到了不同的体液免疫反应。异种移植诱导的体液免疫反应最强，其次是异基因和同基因给药，顺序依次如此。干细胞大多存在于脾脏而非甲状腺中。这种迁移可能是因为干细胞主要在全身免疫调节中发挥作用，这是由于在疾病诱导之前给药所致。在本研究中，我们证实了同基因和异基因移植中脂肪组织来源的干细胞在治疗自身免疫性甲状腺炎方面具有相同的效果。
