Usach Vanina, Casadei Mailin, Piñero Gonzalo, Vence Marianela, Soto Paula, Cueto Alicia, Brumovsky Pablo Rodolfo, Setton-Avruj Clara Patricia
Cátedra de Química Biológica Patológica, Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires C1113AAD, Argentina.
Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires C1113AAD, Argentina.
Int J Mol Sci. 2024 Nov 21;25(23):12482. doi: 10.3390/ijms252312482.
After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study, we analyze whether there is a temporal window in which BMMCs migrate more efficiently to damaged nerves while still retaining their positive effects. Adult Wistar rats of both sexes, with sciatic nerve crush, were systemically transplanted with BMMC at different days post injury. Vehicle-treated, naïve, and sham rats were also included. Morphological, functional, and behavioral analyses were performed in nerves from each experimental group at different survival times. BMMC transplantation between 0 and 7 days after injury resulted in the largest number of nested cells within the injured sciatic nerve, which supports the therapeutic value of BMMC administration within the first week after injury. Most importantly, later BMMC administration 7 days after sciatic nerve crush was associated with neuropathic pain reversion, improved morphological appearance of the damaged nerves, and a tendency toward faster recovery in the sciatic functional index and electrophysiological parameters. Our results thus support the notion that even delayed BMMC treatment may represent a promising therapeutic strategy for peripheral nerve injuries.
周围神经损伤后，轴突和髓鞘再生是实现最佳临床改善的关键事件。我们之前已经表明，早期骨髓单个核细胞（BMMC）移植对髓鞘再生具有有益作用。在本研究中，我们分析是否存在一个时间窗，在此期间BMMC能更有效地迁移至受损神经，同时仍保持其积极作用。对成年雄性和雌性Wistar大鼠进行坐骨神经挤压损伤，并在损伤后的不同天数对其进行BMMC全身移植。还纳入了接受赋形剂处理的未受伤大鼠和假手术大鼠。在不同存活时间对每个实验组的神经进行形态学、功能和行为分析。损伤后0至7天进行BMMC移植，导致损伤的坐骨神经内出现最多数量的巢状细胞，这支持了在损伤后第一周内给予BMMC的治疗价值。最重要的是，在坐骨神经挤压损伤7天后给予BMMC与神经性疼痛逆转、受损神经形态外观改善以及坐骨神经功能指数和电生理参数更快恢复的趋势相关。因此，我们的结果支持这样一种观点，即即使是延迟的BMMC治疗也可能是一种有前景的周围神经损伤治疗策略。
