ReviewApoptosis : an international journal on programmed cell death2026
Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.
Review in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
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Abstract
introductionIntervertebral disc degeneration (IVDD) is a predominant cause of low back pain, and mesenchymal stem cell (MSC) transplantation represents a promising therapeutic strategy. However, its efficacy is severely limited by the harsh oxidative microenvironment of the degenerative disc, which rapidly triggers ferroptosis, an iron-dependent form of cell death, in transplanted MSCs.
methodThis review critically appraised current ferroptosis-inhibition strategies, highlighting their transient or single-axis limitations. We then synthesized a hierarchical framework for engineering robust MSC resistance, progressing from dual-target gene circuits and genetic-pharmacological alliances to smart, protective biomaterial niches.
resultConventional approaches provide only partial protection. In contrast, advanced multi-layered strategies, including dual-target gene circuits (e.g., the Prominin-2/FBXO22/BACH1 axis) potentiated by genetic-pharmacological alliances (e.g., with TBE56), confer superior, cell-intrinsic resilience, increasing MSC survival by approximately 1.5-fold and significantly improving regenerative outcomes in IVDD models. Furthermore, encapsulating engineered MSCs in responsive biomaterials establishes a protective niche, ensuring sustained function.
conclusionThe paradigm is shifting from passive protection to active cellular empowerment. Engineering MSCs with multi-layered, comprehensive ferroptosis shielding is fundamental to unlocking their full therapeutic potential. This engineered cellular empowerment strategy represents a paradigm shift from palliative care to potentially curative, regenerative treatment for IVDD, with the potential to fundamentally change clinical management by addressing the root cause of MSC therapy failure.
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Registered trials
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