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人牙髓干细胞条件培养基通过抑制小胶质细胞焦亡治疗脊髓损伤。

Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis.

作者信息

Liu Tao, Ma Ziqian, Liu Liang, Pei Yilun, Wu Qichao, Xu Songjie, Liu Yadong, Ding Nan, Guan Yun, Zhang Yan, Chen Xueming

机构信息

Department of Orthopedic Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China.

Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.

出版信息

Neural Regen Res. 2024 May;19(5):1105-1111. doi: 10.4103/1673-5374.385309.

Abstract

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury. However, whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear. In the present study, we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells. We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury, decreased expression of the microglial pyroptosis markers NLRP3, GSDMD, caspase-1, and interleukin-1β, promoted axonal and myelin regeneration, and inhibited the formation of glial scars. In addition, in a lipopolysaccharide-induced BV2 microglia model, conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1β pathway. These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1β pathway, thereby promoting the recovery of neurological function after spinal cord injury. Therefore, conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

摘要

人牙髓干细胞移植已被证明是治疗脊髓损伤的有效策略。然而,人牙髓干细胞分泌组是否有助于脊髓损伤后的功能恢复仍不清楚。在本研究中,我们基于重物撞击建立了大鼠脊髓损伤模型,然后给大鼠腹腔注射人牙髓干细胞条件培养基。我们发现,该条件培养基有效促进了脊髓损伤大鼠的感觉和运动功能恢复,降低了小胶质细胞焦亡标志物NLRP3、GSDMD、半胱天冬酶 - 1和白细胞介素 - 1β的表达,促进了轴突和髓鞘再生,并抑制了胶质瘢痕的形成。此外,在脂多糖诱导的BV2小胶质细胞模型中,人牙髓干细胞条件培养基通过抑制NLRP3/半胱天冬酶 - 1/白细胞介素 - 1β途径保护细胞免于焦亡。这些结果表明,人牙髓干细胞条件培养基可通过抑制NLRP3/半胱天冬酶 - 1/白细胞介素 - 1β途径减少小胶质细胞焦亡,从而促进脊髓损伤后神经功能的恢复。因此,人牙髓干细胞条件培养基可能成为脊髓损伤的替代疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cd7/10749599/0130cc6e16ec/NRR-19-1105-g002.jpg

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