State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 14, 3rd Sec., Ren Min Nan Road, Chengdu, 610041, China.
Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Stem Cell Res Ther. 2021 Mar 22;12(1):202. doi: 10.1186/s13287-021-02237-5.
The low survival rate or dysfunction of extracellular matrix (ECM)-based engineered organs caused by the adverse effects of unfavourable local microenvironments on seed cell viability and stemness, especially the effects of excessive reactive oxygen species (ROS), prompted us to examine the importance of controlling oxidative damage for tissue transplantation and regeneration. We sought to improve the tolerance of seed cells to the transplant microenvironment via antioxidant pathways, thus promoting transplant efficiency and achieving better tissue regeneration.
We improved the antioxidative properties of ECM-based bioroots with higher glutathione contents in dental follicle stem cells (DFCs) by pretreating cells or loading scaffolds with the antioxidant NAC. Additionally, we developed an in situ rat alveolar fossa implantation model to evaluate the long-term therapeutic effects of NAC in bioroot transplantation.
The results showed that NAC decreased HO-induced cellular damage and maintained the differentiation potential of DFCs. The transplantation experiments further verified that NAC protected the biological properties of DFCs by repressing replacement resorption or ankylosis, thus facilitating bioroot regeneration.
The following findings suggest that NAC could significantly protect stem cell viability and stemness during oxidative stress and exert better and prolonged effects in bioroot intragrafts.
由于不利的局部微环境对种子细胞活力和干性的负面影响,特别是过量活性氧 (ROS) 的影响,基于细胞外基质 (ECM) 的工程器官的存活率低或功能障碍,促使我们检查控制氧化损伤对于组织移植和再生的重要性。我们试图通过抗氧化途径提高种子细胞对移植微环境的耐受性,从而提高移植效率并实现更好的组织再生。
我们通过预处理细胞或用抗氧化剂 NAC 负载支架,提高了富含谷胱甘肽的牙周膜干细胞 (DFC) 中基于 ECM 的生物牙根的抗氧化特性。此外,我们开发了一种原位大鼠牙槽窝植入模型,以评估 NAC 在生物牙根移植中的长期治疗效果。
结果表明,NAC 可减少 HO 诱导的细胞损伤并维持 DFC 的分化潜能。移植实验进一步证实,NAC 通过抑制替代吸收或粘连来保护 DFC 的生物学特性,从而促进生物牙根的再生。
这些发现表明,NAC 可在氧化应激期间显著保护干细胞活力和干性,并在生物牙根内发挥更好和更持久的作用。