MIF调控干细胞诱导的巨噬细胞表型转化控制畸胎瘤形成的分子机制

Stem cells transplantation is the most hopeful method for treating spinal cord injury . However, stem cells are generally limited in their plasticity as their pluripotency can also lead to risk of teratoma formation after transplantation, which is a major obstacle for clinical application. To effectively reduce the risk of teratomas following grafting of stem cells, we propose to explore the strategy to control teratoma development after stem cell transplantation in spinal cord. Our preliminary study indicated that MIF and infiltrating macrophages in the formation process of teratoma after stem cells transplantation has played an important role. In order to further clarify the mechanism of MIF promoting angiogenesis in teratoma formation, and control MIF expression targeting M2, to inhibit angiogenesis and reduce the rate of teratoma development resulting from stem cell transplantation effectively. We plan to use MIF knockout and bone marrow chimeric mouse model, RT-PCR, immunohistochemical technology and flow cytometry instrument and gene chip analysis etc, to explore the mechanism of stem cell changing the microenvironment of spinal cord so to promote its growth, and lay the foundation of Preventing teratoma development.

干细胞移植治疗脊髓损伤前景良好，但是干细胞的致瘤性严重阻碍了其临床应用，致瘤机制与防治策略需要深入研究。课题组前期研究发现MIF和浸润巨噬细胞在干细胞移植后畸胎瘤的形成过程中发挥了重要作用。为了进一步明确MIF促进血管生成在畸胎瘤形成中的机制，并通过调控MIF表达靶向巨噬细胞M2型实现抑制血管生成，以便有效降低干细胞移植引起的畸胎瘤几率。课题组拟采用MIF敲除及骨髓嵌合体小鼠模型，运用RT-PCR、免疫组化、流式细胞仪、基因芯片分析等技术进行研究,为探索干细胞改变脊髓微环境以促进其生长的机制和预防畸胎瘤的发生奠定基础。

干细胞移植治疗脊髓损伤前景良好，但是干细胞的致瘤性严重阻碍了其临床应用，致瘤机制与防治策略需要深入研究。课题组前期研究发现MIF和浸润巨噬细胞在干细胞移植后畸胎瘤的形成过程中发挥了重要作用。为了进一步明确MIF促进血管生成在畸胎瘤形成中的机制，并通过调控MIF表达靶向巨噬细胞M2型实现抑制血管生成，以便有效降低干细胞移植引起的畸胎瘤几率。课题组采用了MIF敲除及骨髓嵌合体小鼠模型，运用RT-PCR、免疫组化、流式细胞仪、基因芯片分析等技术进行研究, 为探索干细胞改变脊髓微环境以促进其生长的机制和预防畸胎瘤的发生奠定基础。研究结果进一步明确了浸润巨噬细胞在畸胎瘤形成中的作用, 阐明了巨噬细胞MIF促进肿瘤血管生成的机制, 提示了MIF 对巨噬细胞极化的调控在防止干细胞移植后畸胎瘤形成中的作用及其应用前景。