ArticleJournal of the American Heart Association2021
Combination of Antioxidant Enzyme Overexpression and N-Acetylcysteine Treatment Enhances the Survival of Bone Marrow Mesenchymal Stromal Cells in Ischemic Limb in Mice With Type 2 Diabetes.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Integrated Phenotypic and Transcriptomic Analyses of Osteoporosis in Type 2 Diabetic Mice.International journal of medical sciences · 2025Article
- Modulation of Stem Cell Survival and Engraftment: Implications for Stem Cell-Based Therapy.Theranostics · 2025Review
- Oxidative Stress, Endothelial Dysfunction, andAntioxidants & redox signaling · 2024Review
- Treatment of type 2 diabetes mellitus with stem cells and antidiabetic drugs: a dualistic and future-focused approach.Human cell · 2024Review
- An Innovative Delivery System of Oxygen-Releasing Nanospheres and Self-Healing Hydrogels Enhances the Therapeutic Effectiveness of Bone Marrow Mesenchymal Stem Cells for Chronic Limb-Threatening Ischemia.International journal of nanomedicine · 2024Article
- N-Acetylcysteine and Atherosclerosis: Promises and Challenges.Antioxidants (Basel, Switzerland) · 2023Review
- ROS are evolutionary conserved cell-to-cell stress signals.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases.Bioactive materials · 2023Review
- Osteogenesis of bone marrow mesenchymal stem cell in hyperglycemia.Frontiers in endocrinology · 2023Review
- CARD9 deficiency improves the recovery of limb ischemia in mice with ambient fine particulate matter exposure.Frontiers in cardiovascular medicine · 2023Article
- Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-β1.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- N‑acetyl cysteine prevents ambient fine particulate matter‑potentiated atherosclerosis via inhibition of reactive oxygen species‑induced oxidized low density lipoprotein elevation and decreased circulating endothelial progenitor cell.Molecular medicine reports · 2022Article
- Article
- State of the field: cellular and exosomal therapeutic approaches in vascular regeneration.American journal of physiology. Heart and circulatory physiology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Background Therapy with mesenchymal stem cells remains a promising but challenging approach to critical limb ischemia in diabetes because of the dismal cell survival. Methods and Results Critical limb ischemia in type 2 diabetes mouse model was used to explore the impact of diabetic limb ischemia on the survival of bone marrow mesenchymal stromal cells (bMSCs). Inhibition of intracellular reactive oxygen species was achieved with concomitant overexpression of superoxide dismutase (SOD)-1 and glutathione peroxidase-1 in the transplanted bMSCs, and extracellular reactive oxygen species was attenuated using SOD-3 overexpression and N-acetylcysteine treatment. In vivo optical fluorescence imaging and laser Doppler perfusion imaging were used to track cell retention and determine blood flow in diabetic ischemic limb, respectively. Survival of the transplanted bMSCs was significantly decreased in diabetic ischemic limb compared with the control. In vitro study indicated that advanced glycation end products, not high glucose, significantly decreased the proliferation of bMSCs and increased their apoptosis associated with increased reactive oxygen species production and selective reduction of SOD-1 and SOD-3. In vivo study demonstrated that concomitant overexpression of SOD-1, SOD-3, and glutathione peroxidase-1, or host treatment with N-acetylcysteine, significantly enhanced in vivo survival of transplanted bMSCs, and improved critical limb ischemia in diabetic mice. Combination of triple antioxidant enzyme overexpression in bMSCs with host N-acetylcysteine treatment further improved bMSC survival with enhanced circulatory and functional recovery from diabetic critical limb ischemia. Conclusions Simultaneous suppression of reactive oxygen species from transplanted bMSCs and host tissue could additively enhance bMSC survival in diabetic ischemic limb with increased therapeutic efficacy in diabetes.
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