Matsuoka Akihiro J, Kondo Takako, Miyamoto Richard T, Hashino Eri
Department of Otolaryngology-Head and Neck Surgery, Stark Neurosciences Research Institute, Indiana University School of Medicine, 699 West Drive, Indianapolis, IN 46202, USA.
Laryngoscope. 2006 Aug;116(8):1363-7. doi: 10.1097/01.mlg.0000225986.18790.75.
OBJECTIVES/HYPOTHESIS: Stem cell replacement therapy has the potential to treat or cure an array of degenerative neurologic disorders, including sensorineural deafness. However, little is known about the potential for marrow-derived stem cells (MSCs) to take on properties of spiral ganglion neurons. The main purpose of this prospective animal study was to evaluate the survival of MSCs transplanted into the gerbil cochlea.
Eight 3- to 4-month-old Mongolian gerbils were used as recipients. The animals received an intraperilymphatic transplantation of 100,000 green fluorescent protein (GFP)-positive MSCs with scala tympani injection and modiolar injection. Seven days after transplantation, MSC survival was evaluated by microscopic examination of frozen sections cut through the cochleae of the recipient animals.
MSCs isolated from the TgN (ACTbEGFP) mouse line used in this study exhibited bright green florescence after five to seven passages in vitro. Seven days after postoperatively, most transplanted MSCs were found in the scala tympani and scala vestibule and only a small number located in the scala media in animals that received both forms of injection. There were no GFP-positive MSCs in the modiolus in animals with scala tympani injection. In contrast, the mean profile count in animals with modiolar injection was 28, which was the highest in all regions. Although MSCs have the potential to migrate, the anatomic barrier between the perilymphatic space and the modiolus might account for the absence of GFP-positive MSCs in this region.
These findings may have important clinical implications as a means of delivering MSCs in the cochlea for cell replacement therapy.
目的/假设:干细胞替代疗法有潜力治疗或治愈一系列退行性神经疾病,包括感音神经性耳聋。然而,关于骨髓源性干细胞(MSC)具备螺旋神经节神经元特性的潜力,人们了解甚少。这项前瞻性动物研究的主要目的是评估移植到沙鼠耳蜗中的MSC的存活情况。
八只3至4个月大的蒙古沙鼠作为受体。这些动物通过鼓阶注射和蜗轴注射接受了100,000个绿色荧光蛋白(GFP)阳性MSC的内淋巴移植。移植后7天,通过对受体动物耳蜗的冰冻切片进行显微镜检查来评估MSC的存活情况。
本研究中使用的从TgN(ACTbEGFP)小鼠品系分离的MSC在体外传代五到七次后呈现明亮的绿色荧光。术后7天,在接受两种注射方式的动物中,大多数移植的MSC位于鼓阶和前庭阶,只有少数位于中阶。接受鼓阶注射的动物的蜗轴中没有GFP阳性MSC。相比之下,接受蜗轴注射的动物的平均轮廓计数为28,是所有区域中最高的。尽管MSC有迁移的潜力,但内淋巴间隙和蜗轴之间的解剖屏障可能是该区域缺乏GFP阳性MSC的原因。
这些发现作为在耳蜗中递送MSC进行细胞替代治疗的一种手段,可能具有重要的临床意义。