转基因造血干细胞骨髓归巢并调控骨骼细胞成骨治疗骨质疏松的机制研究

Osteoporosis is becoming an overall crisis to human being health as aging problem is increasingly sever. Up to now, medication is the main medical intervention for this issue. However, there are disadvantages for this therapy such as lack of tissue specific effects on bone, accumulating side effects and inadequate efficiency. On the contrary, cell based therapy showed high efficiency and tissue specificity, which brings to us that it may be a new strategy for osteoporosis treatment. Furthermore, it is shown recently that Wnt10b protein plays a critical role in promoting osteogenic differentiation ability of Mesenchymal Stem/Progenitor cells (MSCs) in the bone marrow, niche to be specific. In addition, our preliminary data showed that Hematopoietic Stem Cells (HSCs) has the ability of homing to bone marrow, forming the niche with MSCs, and thus regulate its differentiation ability. Based on this, we hypothesized that HSCs transfected with Wnt10b could home to bone marrow and secrete Wnt10b, and thus be able to promote osteogenic differentiation of MSCs, which could be used for osteoporosis treatment. By doing so, we aim to learn the mechanism how Wnt10b regulate the MSCs differentiation ability in the bone marrow niche, which could pave the road for cell therapy on osteoporosis and thus bring up a new strategy for osteoporosis treatment.

骨质疏松症正成为老龄化国家日益严重的的全民健康问题。当前，骨质疏松症主要依靠药物治疗，但现有药物均存在缺乏靶向性、全身副反应多、治疗效果差等弊端。干细胞治疗在多种疾病的治疗中体现出优异的靶向性和高效性，可能成为骨质疏松治疗的新手段；前期研究证实造血干细胞具有靶向骨髓归巢并与骨髓微环境中的间充质干细胞形成密切生态结构从而相互影响的能力，另外，新近研究显示Wnt信号在调控骨髓间充质干细胞向成骨方向分化并成骨的过程中起到核心作用，据此我们设想利用造血干细胞携带Wnt10b基因靶向归集到骨质疏松的骨组织并在骨髓微环境中分泌Wnt10b蛋白，调控间充质干细胞等成骨细胞系细胞成骨分化，从而进行骨骼生态微环境成骨治疗骨质疏松的研究，阐明骨骼微环境成骨过程中，Wnt10b对成骨细胞系细胞、造血干细胞的调控机制，为骨质疏松的细胞治疗奠定基础，提供骨质疏松症治疗的新思路。

随着我国进入老龄化社会，骨质疏松症正在成为我国的一大全民健康问题。目前骨质疏松症主要依靠药物治疗，但是目前批准上市的药物存在诸如靶向性差、副作用多等弊端。干细胞治疗在多种疾病中体现出了良好的靶向性和疗效，有希望成为骨质疏松症治疗的新手段。在本项研究中，我们证明了Wnt10b信号通路具有高效的促进成骨作用，构建了能够过表达Wnt10b蛋白的人脐带间充质干细胞，在体外证明其能促进骨生成及血管生成，在体内能够局部促进骨折愈合，阐明了成骨微环境中Wnt10对于成骨细胞系、血管内皮细胞的调控机制，发表了2篇SCI，为其进一步应用于全身，治疗全身性的骨质疏松提供了理论基础，开拓出了细胞治疗骨质疏松的新思路。