Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway

Liu, Jie; Huang, Jingyao; Zhang, Zhenjiang; Zhang, Rui; Sun, Qijuan; Zhang, Zhihao; Liu, Yongxin; Ma, Baoyu

doi:10.1155/2022/3593294

Cited by 29 publications

(20 citation statements)

References 77 publications

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“…Although no study has explored the potential regulatory effects of MSCs on renal and intestinal ferroptosis after regional or systemic IR injury, two studies have demonstrated that MSCs could ameliorate regional cerebral IR injury by inhibiting cell ferroptosis through regulating the GPX4/cyclooxygenase-2 axis (33) and alleviate systemic cardiac and cerebral IR injuries by suppressing ACSL4/GPX4-mediated cell ferroptosis (18). In addition, MSCs have been shown to produce effective protection through the inhibition of cell ferroptosis in some other diseases including acute spinal cord injury, mild traumatic brain injury, erectile dysfunction, and senescence (34)(35)(36)(37). Based on the evidence mentioned previously, the phenomenon of cell ferroptosis mediated by the ACSL4/GPX4 pathway and its potential regulation by MSCs were investigated in the kidney and intestine after CA/CPR in this study.…”

Section: Discussionmentioning

confidence: 99%

“…The working parameters of ventilator were as follows: tidal volume (10 mL/kg), peak flow (40 L/min), and oxygen concentration (21%). In addition, the respiratory frequency was adjusted to maintain a normal range of end-tidal CO 2 (35)(36)(37)(38)(39)(40). Electrocardiograms and oxygen saturation were monitored regularly using a patient monitoring system (BeneVision N22; Mindray, Shenzhen, China).…”

Section: Surgical Preparationmentioning

confidence: 99%

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Effects of Mesenchymal Stem Cells on Postresuscitation Renal and Intestinal Injuries in a Porcine Cardiac Arrest Model

Chen¹,

Ma²,

Liao³

et al. 2023

Shock

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Objectives: Systemic ischemia-reperfusion triggered by cardiac arrest (CA) and resuscitation often causes postresuscitation multiple organ injuries. Mesenchymal stem cells (MSCs) have been proven to be a promising treatment for regional renal and intestinal ischemia reperfusion injuries. This study aimed to investigate the effects of MSCs on renal and intestinal injuries after cardiopulmonary resuscitation (CPR) in a porcine CA model. Methods: Twenty-two male pigs were randomly assigned to the sham (n = 6), CA/CPR (n = 8), and CA/CPR + MSC (n = 8) groups. Mesenchymal stem cells were differentiated from human embryonic stem cells and then intravenously administered at a dose of 2.5 × 106/kg at 1.5 and 3 d before the CA/CPR procedure. The experimental model was established by 8 min of untreated CA, followed by 8 min of CPR. Renal and intestinal injuries were evaluated based on the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid–binding protein, and diamine oxidase at 1, 2, 4, and 24 h after resuscitation. At the end of the experiment, pathological damage was determined by cell apoptosis and ferroptosis in the renal and intestinal tissues. Results: During CPR, five pigs in the CA/CPR group and seven pigs in the CA/CPR + MSC group were successfully resuscitated. After resuscitation, the serum levels of creatinine, serum urea nitrogen, intestinal fatty acid–binding protein, and diamine oxidase were significantly increased in the CA/CPR and CA/CPR + MSC groups compared with those in the sham group. However, MSC administration significantly decreased the levels of renal and intestinal injury biomarkers compared with those in the CA/CPR group. Cell apoptosis and ferroptosis, which were indicated by the levels of apoptotic cells, iron deposition, lipid peroxidation, antioxidants, and ferroptosis-related proteins, were observed in renal and intestinal tissues after resuscitation in the CA/CPR and CA/CPR + MSC groups. Nevertheless, both were significantly milder in the CA/CPR + MSC group than in the CA/CPR group. Conclusions: MSC administration was effective in alleviating postresuscitation renal and intestinal injuries possibly through inhibition of cell apoptosis and ferroptosis in a porcine CA model.

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Section: Discussionmentioning

confidence: 99%

Section: Surgical Preparationmentioning

confidence: 99%

Effects of Mesenchymal Stem Cells on Postresuscitation Renal and Intestinal Injuries in a Porcine Cardiac Arrest Model

Chen¹,

Ma²,

Liao³

et al. 2023

Shock

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show abstract

“…In the field of treating neurological diseases, stem cell technology has been viewed as a viable therapeutic method since the 1980s, when it was used on Parkinson's disease patients and showed encouraging results 36,37 . In light of this, mesenchymal stromal cells (MSCs)‐based therapies have garnered a lot of interest because to their low immunogenicity, ease of ex vivo multiplication, and isolation from a variety of adult tissues.…”

Section: Mscs and Neurological Diseasesmentioning

confidence: 99%

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke

Saleh,

Majeed,

Margiana

et al. 2024

Cell Biochemistry & Function

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Cerebral ischemic damage is prevalent and the second highest cause of death globally across patient populations; it is as a substantial reason of morbidity and mortality. Mesenchymal stromal cells (MSCs) have garnered significant interest as a potential treatment for cerebral ischemic damage, as shown in ischemic stroke, because of their potent intrinsic features, which include self‐regeneration, immunomodulation, and multi‐potency. Additionally, MSCs are easily obtained, isolated, and cultured. Despite this, there are a number of obstacles that hinder the effectiveness of MSC‐based treatment, such as adverse microenvironmental conditions both in vivo and in vitro. To overcome these obstacles, the naïve MSC has undergone a number of modification processes to enhance its innate therapeutic qualities. Genetic modification and preconditioning modification (with medications, growth factors, and other substances) are the two main categories into which these modification techniques can be separated. This field has advanced significantly and is still attracting attention and innovation. We examine these cutting‐edge methods for preserving and even improving the natural biological functions and therapeutic potential of MSCs in relation to adhesion, migration, homing to the target site, survival, and delayed premature senescence. We address the use of genetically altered MSC in stroke‐induced damage. Future strategies for improving the therapeutic result and addressing the difficulties associated with MSC modification are also discussed.

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“…Mechanistically, exosomes activated SIRT1, increasing the expression of Nrf2 and HO-1 and promoting the levels SLC7A11, GPX4, and GSH while suppressing ROS, MDA, and Fe 2+ levels. 65 The C-C motif chemokine receptor-2 (CCR2) is reportedly highly expressed in cancer cells and correlated with poor prognosis. 66 It was shown that glutamicoxaloacetic transaminase 1 (GOT1) from tumor-derived exosomes could upregulate CCR2 to stimulate the Nrf2-HO-1 pathway, resulting in increased GPX4 and decreased ROS, MDA, and Fe 2+ levels to hinder ferroptosis and eventually promoted tumor cell migration and invasion.…”

Section: Nrf2-ho-1 Signalingmentioning

confidence: 99%

The engineered exosomes targeting ferroptosis: A novel approach to reverse immune checkpoint inhibitors resistance

Chen,

Zhang,

Jiang

et al. 2024

Intl Journal of Cancer

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Immune checkpoint inhibitors (ICIs) have been extensively used in immunological therapy primarily due to their ability to prolong patient survival. Although ICIs have achieved success in cancer treatment, the resistance of ICIs should not be overlooked. Ferroptosis is a newly found cell death mode characterized by the accumulation of reactive oxygen species (ROS), glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, which has been demonstrated to be beneficial to immunotherapy and combining ferroptosis and ICIs to exploit new immunotherapies may reverse ICIs resistance. Exosomes act as mediators in cell‐to‐cell communication that may regulate ferroptosis to influence immunotherapy through the secretion of biological molecules. Thus, utilizing exosomes to target ferroptosis has opened up exciting possibilities for reversing ICIs resistance. In this review, we summarize the mechanisms of ferroptosis improving ICIs therapy and how exosomes regulate ferroptosis through adjusting iron metabolism, blocking the ROS accumulation, controlling ferroptosis defense systems, and influencing classic signaling pathways and how engineered exosomes target ferroptosis and improve ICIs efficiency.

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Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway

Cited by 29 publications

References 77 publications

Effects of Mesenchymal Stem Cells on Postresuscitation Renal and Intestinal Injuries in a Porcine Cardiac Arrest Model

Effects of Mesenchymal Stem Cells on Postresuscitation Renal and Intestinal Injuries in a Porcine Cardiac Arrest Model

Therapeutic gene delivery by mesenchymal stem cell for brain ischemia damage: Focus on molecular mechanisms in ischemic stroke

The engineered exosomes targeting ferroptosis: A novel approach to reverse immune checkpoint inhibitors resistance

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