ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
SOD2 promotes the immunosuppressive function of mesenchymal stem cells at the expense of adipocyte differentiation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Yoda1-Functionalized Nanozymes Coordinate Piezo1 Activation and Mitochondrial Protection to Reprogram the Diabetic Osteoimmune Micromilieu and Promote Vascularized Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rewiring Adipocyte Plasticity: The Redox-Mitochondrial Axis as a Driver of Beige Fat Immunometabolism and Adipose Inflammation.Biomolecules · 2026Review
- Article
- Engineering Approaches to Modify Immunomodulatory Functions of Mesenchymal Stromal Cells (MSCs): Tissue Regeneration and Clinical Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mitochondria-targeted strategies in cancer radiotherapy: from ROS regulation to immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Effects of rumen-protected guanidinoacetic acid on fat deposition, antioxidant capacity, fatty acid profiles in subcutaneous adipose of Tibetan sheep: integrated RNA-seq and LC-MS/MS analysis.Frontiers in veterinary science · 2026Article
- Adipose-derived mesenchymal stromal cell-microenvironment interaction network in metabolic syndrome: ADMSC injury response, adaptive regulation, and regenerative potential.Frontiers in cell and developmental biology · 2026Review
- Article
- Mesenchymal stem cell application in Alzheimer's disease.Regenerative therapy · 2025Review
- Mesenchymal Stem Cell-Mediated Targeted Drug Delivery Systems for Hepatocellular Carcinoma: Current Advances and Future Directions.Bioengineering (Basel, Switzerland) · 2025Review
- Dendrobine alleviates CClChinese medicine · 2025Article
- PARP inhibition augments immunomodulatory function of mesenchymal stem/stromal cells by promoting STAT1 phosphorylation.Stem cell research & therapy · 2025Article
- From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.Stem cell research & therapy · 2025Review
- Evolution of cell therapies derived from adipose tissue: historical perspectives, current development trends and future directions.Biology direct · 2025Review
- Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions.International journal of molecular sciences · 2025Review
- Tumor Immunosenescence Driven by Chronic Inflammation: Mechanisms, Microenvironment Remodeling and Therapeutic Strategies.Aging and disease · 2025Review
- Mechanical sensing protein PIEZO1 controls osteoarthritis via glycolysis mediated mesenchymal stem cells-Th17 cells crosstalk.Cell death & disease · 2025Article
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- Autophagic flux-lipid droplet biogenesis cascade sustains mitochondrial fitness in colorectal cancer cells adapted to acidosis.Cell death discovery · 2025Article
- Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.