食蟹猴骨髓源性神经干细胞自体脑内移植的研究

Experimental study on autotransplantation into brain of neural stem cell derived from bone marrow of crab-eating macaque

目的探讨食蟹猴自体骨髓基质细胞诱导分化成神经干细胞后移植到脑内的生长情况.方法对6只食蟹猴进行骨髓基质干细胞体外培养、诱导分化成神经干细胞,经BrdU标记后进行自体脑移植.动物分为即时移植组和延迟移植组,采用立体定向多点注射的方法将神经干细胞悬液移植到猴皮层创伤灶.结果HE染色显示即时移植和延迟移植的创伤区细胞数量都明显多于假移植治疗对照;免疫组织化学染色显示两组动物在干细胞移植后1～6个月脑皮层创伤灶内均有BrdU阳性表达细胞,移植后半年的动物在移植区邻近的脑白质内也可观察到有BrdU阳性表达的细胞,而创伤对照动物、假移植治疗动物和正常脑组织中则未见BrdU阳性表达. 结论BMSCs体外培养得到的神经干细胞经过自体移植能在脑皮层内存活,并且能增殖、分化和迁移,可成为神经干细胞的替代细胞或来源细胞;干细胞移植到陈旧性的脑皮层损伤灶也具有成活、增殖和迁移能力.

Objective To explore the proliferation, growth and migration of neural stem cells (NSCs) derived from crab-eating macaque's bone marrow stromal cells (BMSCs) after autotransplantation into the brain. Methods The NSCs derived from 6 adult Macaque's BMSCs, which were cultured, induced and marked with Bromodeoxyuridine (BrdU), had been autotransplanted into cortical traumatic section and peripheral brain tissue at several points, with the assistance of stereotactic technique. All macaques had been divided into 2 groups: the immediate transplant group and the delayed transplant group. Results The proliferation of post-transplant NSCs in the cortical traumatic section was observed obviously, while in the traumatic section without transplantation NSCs had only colloid proliferation and the cells were evidently fewer than ones of the transplant groups. Immunohistochemistry indicated that there were BrdU-positive cell expression in the cortical traumatic section within 1~6 months after autotransplantation. After 6 months, BrdU-positive cells were also found in the white matter near the transplant sections, but couldn't be found in the non-transplant, sham-tansplant groups and the normal brain tissue. Conclusion The NSCs derived from cultured BMSCs are capable of survival, proliferation,differentiation and migration to nearby brain tissue when transplanted into the brain, so they may be a new source of NSCs. If transplanted into obsolete cortical traumatic section, these NSCs derived from BMSCs also have the ability of survival, proliferation and migration.