Remodeling and repair of the damaged brain: the potential and challenges of organoids for ischaemic stroke

Ischemic stroke induces irreversible cerebral tissue damage, a condition exacerbated by the brain's limited endogenous neuroplasticity and inability to regenerate neurons. While neural circuit reorganization holds therapeutic potential, its efficacy is hindered by pathological barriers such as glial scarring, chronic inflammation, and neurotrophic factor deficiency. Although pharmacological and interventional methods for stroke have been well developed, their functional recovery outcomes remain suboptimal. Emerging neural regeneration paradigms, particularly stem cell-based strategies (encompassing neural stem cell transplantation, neural progenitors grafts, and 3D brain organoid implantation), offer novel solutions to these challenges. However, critical limitations persist in conventional stem cell approaches: (1) compromised synaptic integration efficacy hinders functional neural circuit reconstruction; (2) the absence of functional vascular niches coupled with deficient astrocyte-mediated support and extracellular matrix signaling; (3) restricted regenerative capacity despite theoretical multipotent differentiation potential. Recent breakthroughs in cerebral organoid technology have revolutionized neurological disease modeling and neural repair research. Building upon this paradigm shift, our study mechanistically interrogates neuroplastic remodeling processes following ischemic stroke, while critically evaluating the therapeutic efficacy and inherent limitations of stem cell-based interventions. This affirms the critical role of 3D human cerebral organoid transplantation in the reconstruction of neural circuits. Additionally, we further summarize the utility of organoid-based disease models and address associated ethical and societal concerns. Future efforts should prioritize the clinical translation of organoid transplantation for ischemic stroke, aiming to mitigate neurological deficits and restore functional recovery.