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...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-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,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.展开更多
Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was co...Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.展开更多
A study on alkaline sulfite anthraquinone pulping of wheat straw indicated that the addition of formaldehyde could improve fine pulp yield effectively, enhance brightness of unbleached pulp, and decrease kappa number....A study on alkaline sulfite anthraquinone pulping of wheat straw indicated that the addition of formaldehyde could improve fine pulp yield effectively, enhance brightness of unbleached pulp, and decrease kappa number. Finally, the optimum conditions of this process were formed.展开更多
背景:现有研究已经证实外泌体可有效促进牙髓再生,而经预处理来源的外泌体其生物学功能和特性会发生显著改变,对细胞的增殖、迁移和成牙分化产生不同的影响。目的:探讨外泌体及其预处理方式在牙髓再生领域的应用现状,归纳和总结影响外...背景:现有研究已经证实外泌体可有效促进牙髓再生,而经预处理来源的外泌体其生物学功能和特性会发生显著改变,对细胞的增殖、迁移和成牙分化产生不同的影响。目的:探讨外泌体及其预处理方式在牙髓再生领域的应用现状,归纳和总结影响外泌体发挥作用的预处理方式,并阐述外泌体及其预处理方式对牙髓再生的作用。方法:检索万方、中国知网、PubMed和Web of Science数据库中2006-2022年发表的相关文献,以“外泌体,牙髓再生,预处理方式”等为中文检索词,以“Exosomes,Pulp regeneration,Preconditioning method”等为英文检索词进行检索,共纳入78篇文献进行综述分析。结果与结论:①外泌体具有良好的生物相容性、低免疫原性和无细胞毒性等优势,可以通过促进干细胞成牙、成神经和成血管化进而诱导牙髓组织的新生。②经预处理衍生的外泌体可以增强对组织的修复和再生能力,并对再生牙髓的质量有显著影响。③目前应用在牙髓再生领域中的预处理方式包括炎症刺激、低氧诱导、条件培养基和三维培养,其分泌的外泌体均能有效改善再生牙髓的质量,但是不同的预处理方式对牙髓再生的具体效果和机制在未来尚需探索。展开更多
基金supported by the Research Foundation of Technology Committee of Tongzhou District,No.KJ2019CX001(to SX).
文摘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-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,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.
基金funded by Egyptian Cultural and Educational Bureau in London,Egyptian mission sector and ministry of higher education in Egypt(grant No.GAM2649)。
文摘Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.
文摘A study on alkaline sulfite anthraquinone pulping of wheat straw indicated that the addition of formaldehyde could improve fine pulp yield effectively, enhance brightness of unbleached pulp, and decrease kappa number. Finally, the optimum conditions of this process were formed.
文摘背景:现有研究已经证实外泌体可有效促进牙髓再生,而经预处理来源的外泌体其生物学功能和特性会发生显著改变,对细胞的增殖、迁移和成牙分化产生不同的影响。目的:探讨外泌体及其预处理方式在牙髓再生领域的应用现状,归纳和总结影响外泌体发挥作用的预处理方式,并阐述外泌体及其预处理方式对牙髓再生的作用。方法:检索万方、中国知网、PubMed和Web of Science数据库中2006-2022年发表的相关文献,以“外泌体,牙髓再生,预处理方式”等为中文检索词,以“Exosomes,Pulp regeneration,Preconditioning method”等为英文检索词进行检索,共纳入78篇文献进行综述分析。结果与结论:①外泌体具有良好的生物相容性、低免疫原性和无细胞毒性等优势,可以通过促进干细胞成牙、成神经和成血管化进而诱导牙髓组织的新生。②经预处理衍生的外泌体可以增强对组织的修复和再生能力,并对再生牙髓的质量有显著影响。③目前应用在牙髓再生领域中的预处理方式包括炎症刺激、低氧诱导、条件培养基和三维培养,其分泌的外泌体均能有效改善再生牙髓的质量,但是不同的预处理方式对牙髓再生的具体效果和机制在未来尚需探索。
