Comparative evaluation of the effectiveness of systemic and local administration of mesenchymal stem cells in experimental neuropathy

A.-M. V. Yerofeyeva, E. V. Fedorova, S. Rjabceva, A. Molchanova
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Abstract

Objective. Compare the effectiveness of systemic and local administration of adipose-derived mesenchymal stem cells (ADMSC) at a dose of 1х106 cells/kg on nociceptive sensitivity to mechanical and thermal stimuli in rats and changes in histostructure of sciatic nerve and surrounded tissues of affected hind paw in experimental model of peripheral neuropathy of sciatic nerve.Materials and methods. 26 male Wistar rats were used to perform a model of peripheral neuropathy by axotomy of the sciatic nerve. On the 7th day, the experimental animals underwent systemic or local transplantation of ADMSC at a dose of 1x106 cells/kg. Nociceptive responses to mechanical and thermal stimuli were assessed for 90 days, and the histostructure of the sciatic nerve and surrounding tissues was analyzed after systemic and local transplantation of ADMSC.Results. Systemic administration of ADMSC at a dose of 1x106 cells/kg to rats with sciatic nerve axotomy increased the mechanical withdrawal threshold (MWT) by 17.1% and had no effect on the thermal withdrawal latency (TWL). Local administration of ADMSCs in an equivalent dose contributed to the full recovery of the MWT and TWL by the 21st day of the experiment, as well as suppressed the inflammatory reaction in the soft tissues of the operated hind paw of experimental animals.Conclusion. Intramuscular administration of ADMSC into the area of sciatic nerve axotomy of rats was significantly more effective than systemic administration of an equivalent dose of a cell transplant. This method of administration is more appropriate for further studies of the mechanisms of antinociceptive and reparative effects of ADMSCs.
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间充质干细胞在实验性神经病变中全身和局部应用效果的比较评价
目标。比较脂肪源性间充质干细胞(ADMSC)以1х106细胞/kg剂量全身和局部给药对大鼠机械和热刺激伤害性敏感性的影响,以及坐骨神经周围神经病变实验模型坐骨神经及后爪周围组织的组织结构变化。材料和方法。采用雄性Wistar大鼠26只,采用坐骨神经切开术建立周围神经病变模型。第7天,实验动物接受1 × 106细胞/kg剂量的ADMSC全身或局部移植。观察admsc全身和局部移植后90天内对机械和热刺激的伤害性反应,并分析坐骨神经和周围组织的组织结构。以1 × 106个细胞/kg剂量给药坐骨神经切断大鼠,可使机械戒断阈值(MWT)提高17.1%,但对热戒断潜伏期(TWL)无影响。局部等量给药ADMSCs可使实验动物术后第21天MWT和TWL完全恢复,并能抑制实验动物术后后爪软组织的炎症反应。大鼠坐骨神经截骨区肌注ADMSC明显比等量细胞移植全身给药更有效。这种给药方式更适合于进一步研究ADMSCs的抗感知和修复作用机制。
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