Peripheral neuropathy is associated with chronic debilitating pain and is difficult to treat. In this regard, the development of cell therapy of neuropathic pain using adipose-derived mesenchymal stem cells (MSCs) seems to be relevant.The work was devoted to study the impact of adipose-derived allogeneic MSC transplantation on nociceptive reactions in response to mechanical and thermal stimuli and gait parameters in rats with sciatic nerve injury.It is found that a single local injection of MSCs at a dose of 1·106 cells/kg eliminates axotomy-induced mechanical and thermal hyperalgesia on the 14th day after transplantation, contributes to the recovery of the sciatic functional index and the dynamic gait parameters on the 7th day after transplantation, and prevents the development of gait disturbances in the long-term period.
The study of wound-healing effect of the gel substances with 2 and 4 % (w/w) concentrations of the dry extracts of the everlasting flowers and of the littlewale leaves in the ratio 1:1 were carried out.It was found that the skin application of the studied gel substances promoted the formation of the structural and functional regenerate in the area of the wound defect. The studied gel contributed to the significant reduction of the healing duration of the full-thickness linear wounds in rats compared to the control group of animals (without treatment) and to the group of animals that received treatment with the reference listed drug. The use of the studied gels, regardless of the content of the plant extracts in them (2 or 4 % (w/w)), was not accompanied by toxic effects.
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.
Objective. To estimate an anti-nociceptive and regenerative potential of adipose-derived mesenchymal stem cells in experimental post-traumatic neuropathy in rats. Methods. Neuropathic pain was induced by axotomy technique in rat left hind paw (Wistar rats (n=113)). The respective group of subjects received ADMSCs dose of 1×10<sup>6</sup> cells/kg and 2×10<sup>6</sup> cells/kg into the site of sciatic nerve injury at 2 regimens: single (7<sup>th</sup> day post-surgery) and twice (7<sup>th</sup> and 14<sup>th</sup> day post-surgery). Nociceptive responses, as well as histological changes of sciatic nerve and perineural tissue were assessed in dynamics. Results. Sciatic nerve axotomy led to a significant increase of mechanical nociceptive sensitivity of ipsilateral hind paw by 7<sup>th</sup> day, as well as to fibrotic changes of peri- and epineural areas of damaged nerve fibers and to denervation of surrounding muscle tissue and fascia. Local administration of ADMSCs effectively abolished mechanical hyperalgesia by 14<sup>th</sup> day after first injection at all regimens tested. Among tested regimens, the most pronounced anti-nociceptive and regenerative effects were induced by single injection of ADMSCs (1×10<sup>6</sup> cells/kg). As the dose and frequency of ADMSCs administration elevated, their reparative and anti-inflammatory properties reduced. Conclusion. Obtained results testify anti-nociceptive potential of ADMSCs and feasibility of its further investigation on the experimental models of neuropathy. What this paper adds For the first time the impact of different regimen of allogenic adipose-derived mesenchymal stem cells (ADMSCs) transplantation on nociceptive sensitivity and microstructure changes of sciatic nerve in rats with peripheral neuropathy has been studied. Allogenic transplantation of mesenchymal stem cells at a dose of 1×10<sup>6</sup> cells/kg has been found out to exhibit the most powerful anti-nociceptive and regenerative effects with a single local injection confirmed by algometry and histological study.
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