骨髓造血细胞抑制间质干细胞向脂肪细胞分化的实验研究

Hematopoietic cells (HC) and hemopoietic microenvironment both are the basis of the hematopoietic system, both interact with and influence each other. Though numerous studies have indicated that mesenchymal stem cells (MSCs) can regulate and support hematopoiesis, further work must be carried out to better understand the interaction between HC and MSC. Our previous experiments have showed that the inhibition of hematopoiesis by radiation and myeloablative drugs can promote bone marrow adipogenesis, which was partly inhibited by bone marrow HSC transplantation. All of these revealed HC regulate hemopoietic microenvironment and play a important role in hematopoiesis. In this project, we plan to use Gene chip, Protein chip or other technologies, analyse the critical factors and signaling pathways in the process of HSC isolated by Immunomagnetic Beads or mouse leukemia cells inhibiting mouse MSC or 3T3-L1 cell adipogenesis. Thus, we will define the inhibitory effects of HC on MSC adipogenesis and find the signaling pathways, get further understand to hematopoietic physiology in bone marrow and explain the phenomenon of marrow adipogenesis in many diseases ,such as aplastic anemia. And it will also help to find a new target for regulating MSC, and provide new ideas for clinical hematopoietic stem cell transplantation.

造血细胞和造血微环境是造血系统主要部分，两者相互作用、相互影响。虽然有大量研究报道间质干细胞（MSC）对造血细胞（HC）的支持调节作用，然而对骨髓HC与MSC相互作用的了解还远远不够。本项目前期实验显示，采用辐射或者清髓药物抑制骨髓造血则促进骨髓脂肪化、而移植骨髓HC则可部分抑制骨髓脂肪分化。这提示HC对微环境的调节作用，提示其在骨髓造血中的主导地位。本项目拟利用基因芯片、蛋白芯片等技术，分析免疫磁珠分离的HSC或者小鼠白血病细胞在体外抑制小鼠MSC或者3T3-L1向脂肪化的关键因子及其信号途径，然后研究观察其体内抑制骨髓脂肪化、促进造血重建作用，以明确HC 对MSC向脂肪细胞分化的调节作用、了解其信号途径，进一步了解骨髓造血生理、解释再生障碍性贫血等疾病骨髓脂肪化现象，为寻找新的调节MSC生物学特性靶点、进行临床应用研究提供依据。

按计划采用辐射或者清髓药物及移植骨髓造血细胞等方式，研究了小鼠骨髓造血细胞、HSC 或者小鼠白血病细胞体外抑制小鼠MSC 或者3T3-L1 向脂肪化的关键因子及其信号途径，并观察其体内抑制骨髓脂肪化、促进造血重建作用，明确或了解了造血细胞对MSC 向脂肪细胞分化的调节作用、其信号途径，揭示了造血细胞在骨髓造血中的主导地位，了解骨髓造血生理、解释再生障碍性贫血等疾病骨髓脂肪化现象，并试探寻找调节MSC 生物学特性的药物，如川续断皂苷Ⅵ、硫酸软骨素、促红细胞生成素和红景天苷等。该结果提供了骨髓造血方面新的基础知识及其可能应用依据,对进一步了解骨髓造血生理、解释再生障碍性贫血等疾病骨髓脂肪化现象，为寻找新的调节MSC生物学特性靶点、进行临床应用研究提供依据。