中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (10): 1603-1609.doi: 10.4103/1673-5374.193239

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

胚胎干细胞静脉注射可减轻ICR远交系小鼠中枢神经脱髓鞘损害

  

  • 收稿日期:2016-09-18 出版日期:2016-10-31 发布日期:2016-10-31
  • 基金资助:
    泰国清迈大学兽医学院基金

Intravenous transplantation of mouse embryonic stem cells attenuates demyelination in an ICR outbred mouse model of demyelinating diseases

Kidsadagon Pringproa1, *, Anucha Sathanawongs1, Chananthida Khamphilai1, Sarocha Sukkarinprom1, Apichart Oranratnachai2   

  1. 1 Department of Veterinary Biosciences and Veterinary Public Heath, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Tailand 2 Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Tailand
  • Received:2016-09-18 Online:2016-10-31 Published:2016-10-31
  • Contact: Kidsadagon Pringproa, D.V.M., M.S., Ph.D., kidsadagon.p@cmu.ac.th
  • Supported by:
    This study was supported by the Faculty Research Fund, Faculty of Veterinary Medicine, Chiang Mai University, Tailand.

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摘要：

双环己酮草酰双腙诱导的中枢神经系统髓鞘脱失BALB/c近交系小鼠模型已广泛用于脱髓鞘疾病机制和治疗的研究，但由于小鼠种系不同，其病理结局也会不同。由于目前对多发性硬化药物治疗的临床效果仍不理想，许多学者已热点关注了细胞移植的治疗方法。实验目的在于检验与人类遗传背景更为接近的ICR远交系小鼠模型是否适用于脱髓鞘疾病的研究，以及胚胎干细胞静脉移植对脱髓鞘疾病的治疗作用。实验分2部分进行。首先，ICR远交系小鼠和BALB/c近交系小鼠均接受0.2%双环己酮草酰双腙喂饲6周，以建立中枢神经脱髓鞘模型，然后应用luxol fast blue染色或CNPase免疫组化进行脱髓鞘评分。其次，将小鼠胚胎干细胞经尾静脉移植于ICR远交系小鼠脱髓鞘模型中，以观察胚胎干细胞减轻中枢神经系统髓鞘脱失的作用。结果表明，双环己酮草酰双腙可诱发ICR远交系小鼠和BALB/c近交系小鼠大脑皮质和胼胝体发生明显的髓鞘脱失，静脉移植胚胎干细胞也明显减轻了ICR远交系小鼠大脑皮质和胼胝体脱髓鞘损害。从而证实，双环己酮草酰双腙诱导的ICR远交系小鼠中枢神经脱髓鞘模型是适用于此类疾病研究较为理想的动物模型，胚胎干细胞移植将有望成为用于中枢神经系统脱髓鞘疾病治疗的方法之一。 

orcid: 0000-0001-7291-1100 (Kidsadagon Pringproa)

关键词: 神经再生, ICR远交系小鼠, 脱髓鞘, 胚胎干细胞, 细胞移植, 动物模型

Abstract: Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always e?ective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. Te aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the e?ects of intravenous cell transplantation in the present developed mouse model. Two sets of experiments were conducted. Firstly, ICR outbred and BALB/c inbred mice were fed with 0.2% cuprizone for 6 consecutive weeks; then demyelinating scores determined by luxol fast blue stain or immunolabeling with CNPase were evaluated. Secondly, attenuation of demyelination in ICR mice by intravenous injection of mES cells was studied. Scores for demyelination in the brains of ICR mice receiving cell injection (mES cells-injected group) and vehicle (sham-inoculated group) were assessed and compared. Te results showed that cuprizone signifcantly induced demyelination in the cerebral cortex and corpus callosum of both ICR and BALB/c mice. Additionally, intravenous transplantation of mES cells potentially attenuated demyelination in ICR mice compared with sham-inoculated groups. Te present study is among the earliest reports to describe the cuprizone-induced demyelination in ICR outbred mice. Although it remains unclear whether mES cells or trophic e?ects from mES cells are the cause of enhanced remyelination, the results of the present study may shed some light on exogenous cell therapy in central nervous system demyelinating diseases.

Key words: nerve regeneration, ICR outbred mice, cuprizone, demyelination, embryonic stem cells, remyelination, immunohistochemistry, neural regeneration