Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jul 10;23(1):767.
doi: 10.1186/s12967-025-06736-4.

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

Affiliations
Review

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

Yi-Xuan Hao et al. J Transl Med. .

Abstract

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.

Keywords: Ischaemic stroke; Neurological recovery; Neuroplasticity; Organoid transplantation; Regenerative medicine; Stem cell therapy.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: None to declare.

Figures

Fig. 1
Fig. 1
The main pathophysiological mechanisms of IS in the acute and convalescent phases. In the acute phase of IS, the ischaemia and reperfusion injury lead to mitochondrial dysfunction, cellular damage, and impairment of the blood–brain barrier. As IS interrupts the normal synaptic plasticity, during the recovery period, homeostatic plasticity is up-regulated and neurogenesis and synaptic remodelling occur. In addition, new synapse formation builds new circuits and aids brain recovery. In the cellular response mode, astrocytes secrete neurotrophic and angiogenic factors to repair damaged blood vessels and nerves. IS ischaemic stroke
Fig. 2
Fig. 2
Comparison of different treatment stratagies for IS. Current treatments for IS include regenerative medicine, tPA, and pharmacological treatments (GABA receptor agonists, glutamate receptor inhibitors, and sodium-calcium channel blockers). NMDA-R N-methyl-d-aspartic acid receptors, GABA-RA gamma-aminobutyric acid receptor agonists, GLU-RI glutamate receptor inhibitors, SCCB sodium and calcium channel blockers, IS ischaemic stroke, tPA tissue plasminogen activator
Fig. 3
Fig. 3
Comparison of Stem Cell Transplantation and Organoid Transplantation in Therapeutic Approaches for Ischemic Stroke. When a stroke occurs, a series of pathological changes take place in the ischemic core region. Transplantation of exogenous stem cells into the brain repairs the damaged BBB and replenishes the neuronal deficit in the brain; transplantation of mature human brain organoids cultured in vitro into the brain not only repairs the damaged BBB and vascularises the organoids, but also promotes the process of neurogenesis, in which neural stem cells and precursor cells continue to generate and differentiate into mature neurons, which subsequently migrate gradually to form the six-layered structure of the cerebral cortex. BBB blood brain barrier
Fig. 4
Fig. 4
Transplantation and functional integration of iPSC-derived brain organoids into the brain. After transplantation of the brain organoids into the mouse brain: the host vascular network invades and nourishes the organoids to achieve vascularisation of the organoids and provide nutrients to the organoids; the human neurons search for the target host neurons through projections and establish functional synaptic connections with them, which generates spontaneous action potentials and triggers excitatory post-synaptic potentials (synaptic remoulding); The organoid grows and differentiates to mimic the motor nerve circuits of the human brain, travelling down through the midbrain, the pons, the medulla oblongata and the spinal cord to complete the corticospinal tracts-a key circuit for locomotion, and the motor nerve circuits are thus reconstructed and integrated. iPSC induced pluripotent stem cells, AMPA-R α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor

Similar articles

References

    1. Feigin VL, Brainin M, Norrving B, et al. World Stroke Organization (WSO): global stroke fact sheet 2022. Int J Stroke Off J Int Stroke Soc. 2022;17(1):18–29. - PubMed
    1. Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67–492. - PubMed
    1. Feigin VL. Stroke: practical management. JAMA. 2008;300(19):2311.
    1. Langhorne P, Coupar F, Pollock A. Motor recovery after stroke: a systematic review. Lancet Neurol. 2009;8(8):741–54. - PubMed
    1. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46–110. - PubMed

LinkOut - more resources