Improvement of ECM-based bioroot regeneration via N-acetylcysteine-induced antioxidative effects

Abstract

Background 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. Methods 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. Results The results showed that NAC decreased H2O2-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. Conclusions 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.

PPAR-γ activation promotes xenogenic bioroot regeneration by attenuating the xenograft induced-oxidative stress

“…Similarly, in the heart transplantation, OS-derived damage contributes to progressive endothelial damage in the coronary arteries, leading to cardiac allograft vasculopathy initiation and progression ( Kargin et al, 2018 ), greatly affecting the tissue remodeling process and function ( Schimke et al, 2000 ). Recently, our study verified an increased regeneration efficiency of the allogenic bioroots with ROS controlling through administrating with NAC ( Zhang et al, 2021 ). Therefore, antioxidant therapy should be a significant component of the patients with organ transplantation ( Szczurek et al, 2020 ).…”

“…The aggravated inflammation in the microenvironment could cause great damage to the cells, contributing to the xenograft failure. For example, when conducting the pancreatic islet transplantation, it is usually accompanied by up-regulated expression of ROS related to the nonspecific inflammatory response ( Eltzschig et al, 2011; Alva et al, 2018; Zhang et al, 2021 ), immune rejection and IRI with persistent redox imbalance ( Yamada et al, 2013 ), which would cause the islet dysfunction and unable to regulate blood glucose in type 1 diabetes mellites treatment.…”

“…An emphasis on ROS control under the situation of promoting renal transplantation survival has been widly proposed during last 20 years since the most serious complications in kidney transplantation often result from OS ( Tejchman et al, 2021; Farina et al, 2019; Yao et al, 2020 ). Similarly, during ECM based bioroots transplantation process, application of antioxidant N-Acetyl-L-cysteine (NAC) has obviously improved the periodontal ligaments (PDLs) regeneration efficiency by preserving the biological function of the transplanted stem cells, verifying the importance of antioxidation in bioroots transplantation ( Zhang et al, 2021 ). In order to acquire an favorable outcome of xenogenic bioroots transplantation, not only controlling the overproduction ROS is essential, but enhancing the host’s ability to defend against immune rejection is also an imperative requirement.…”

BMSC-Derived ApoEVs Promote Craniofacial Bone Repair via ROS/JNK Signaling

“…To confirm the role of ROS in ApoEV-mediated bone regeneration, 5 mM antioxidant N-acetyl-L-cysteine (NAC) was used to eliminate ROS in the ApoEVs and the recipient BMSCs, respectively (Zhang et al 2021). Adding NAC simultaneously with ApoEVs (ApoEVs/NAC) directly into the medium can largely eliminate ROS caused by ApoEVs (Fig.…”

Reactive oxygen species may influence on the crossroads of stemness, senescence, and carcinogenesis in a cell via the roles of APRO family proteins

“…In addition, stem cells are robust to collapse and protected against the responses to various stimulus [14]. However, ROS stimuli have been hypothesized to lead to the loss of the transplanted stem cells [15]. In general, ROS may inhibit the proliferation of stem cells and enhance the differentiation to the specific cells [16] (Figure 1).…”