Targeted KEAP1 Disruption Enhances Antioxidant Defense And Mesenchymal Stromal Cell Therapy For Chronic Limb-threatening Ischemia - PubMed
4 days ago
- #KEAP1
- #Chronic Limb-threatening Ischemia
- #Mesenchymal Stromal Cells
- Chronic limb-threatening ischemia (CLTI) is a severe vascular disorder with tissue hypoxia and oxidative stress.
- Mesenchymal stem/stromal cells (MSCs) show potential for CLTI treatment but are compromised by oxidative stress.
- CRISPR/Cas9 was used to knockout KEAP1 in human bone marrow-derived MSCs to enhance antioxidant defense.
- KEAP1 editing activated the NRF2 pathway, reducing oxidative stress and improving MSC viability and function.
- Edited MSCs showed enhanced secretion of proangiogenic cytokines and improved tissue perfusion in a CLTI mouse model.
- KEAP1 gene editing is a promising strategy to improve MSC therapy for oxidative ischemic conditions.