糖基化改装人脂肪来源干细胞促进其骨髓归巢及成骨的研究

Surface fucosylation of human adipose-derived stem cells(ASCs) augments homing to bone

目的探讨脂肪来源干细胞表达的CD44,可以被糖基化技术进行修饰,成为造血干细胞E/L选择素配体(HCELL),进而可有效的骨髓归巢并原位分化成骨。方法应用α-1,3-唾液盐藻糖酶:FTV以及其底物GDP-海藻糖处理人脂肪来源干细胞,使该细胞表面CD44分子糖基化为HCELL,检测其增殖、分化等细胞生物学特性。平行平板流动腔试验以及免疫荧光染色验证其小鼠体内归巢及成骨能力。结果α-1,3-岩藻糖基化的h ASC在不损害细胞活力的情况下表达HCELL,能够诱导血管内皮细胞表面E-选择素与其结合,并在剪切力条件下,使hASCs与内皮E-选择素产生强大的滚动粘附效应,促进hASCs迁移到骨髓中,并在小鼠骨髓中产生人骨样细胞。结论本研究证明糖基化技术能够增强干细胞的骨髓归巢能力,且不对干细胞自身细胞活性产生负向作用。

Objective To investigate whether the expression of CD44 on adipose-derived stem cells can be modified by glycosylation technology to become hematopoietic stem cell E/L selectin ligand （HCELL）, which effectively enhance bone marrow homing and differentiate into bone. Methods α-1,3-fucosyltransferase （e.g., fucosyltransferase V （FTV） and its substrate GDP-fucose were used to treat human adipose-derived stem cells, so that the cell surface CD44 molecule glycosylated and turned into HCELL, and its cell biology characteristics such as proliferation and differentiation were detected. Parallel plate flow chamber test and immunofluorescence staining confirmed the homing and osteogenic ability of infusion cellls. Results α-1,3-fucosylated hASCs express HCELL without impairing cell viability can induce E-selectin binding on vascular endothelial cells, and make hASCs and endothelials under shear conditions. E-selectin produces a powerful rolling adhesion effect that promotes the migration of hASCs into the bone marrow and produces human osteoblast-lineage cells in the bone marrow of mice. Conclusion This study demonstrates that glycosylation technology can enhance the bone marrow homing ability of stem cells, and does not have a negative effect on stem cell viability.