Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (5): 1105-1111.doi: 10.4103/1673-5374.385309

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

Tao Liu1, #, Ziqian Ma1, #, Liang Liu1, Yilun Pei1, Qichao Wu2, Songjie Xu1, Yadong Liu1, Nan Ding3, Yun Guan4, 5, Yan Zhang1, *, Xueming Chen1, *#br#   

  1. 1Department of Orthopedic Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China; 2Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; 3Department of Stomatology, Beijing Luhe Hospital, Capital Medical University, Beijing, China; 4Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; 5Department of Neurological Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Yan Zhang, MD, PhD, zhangyanorth@mail.ccmu.edu.cn; Xueming Chen, MD, chenxueming@ccmu.edu.cn.
  • Supported by:
    This work was supported by the Research Foundation of Technology Committee of Tongzhou District, No. KJ2019CX001 (to SX).

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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.

Key words: BV2, conditioned medium, dental pulp stem cells, GSDMD, microglia, neuroinflammation, NLRP3, pyroptosis, spinal cord injury