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midbrain organoids could be a promising strategy for the Integrating high-throughput screening technologies, along
clinical treatment of PD. 82,83 with omics-based analysis and artificial intelligence, may

In addition to organoid transplantation, several groups improve drug discovery efforts. Additionally, combining
have investigated the feasibility of transplanting midbrain organoid models with patient-derived iPSCs could
astrocytes or neural stem/precursor cells (NSCs) isolated further personalize PD research and precision medicine
from hMOs (Og-NSCs). 84,85 Astrocytes derived from hMOs approaches.
have been shown to exhibit remarkable neurotrophic In conclusion, while current PD organoid models
and regenerative capacities. Similarly, Og-NSC-derived have significantly advanced our understanding of disease
midbrain DA neurons demonstrated enhanced synaptic mechanisms, continued refinement and integration of
maturity, functionality, resistance to toxic insults, and cutting-edge technologies will be essential to overcoming
stable expression of midbrain-specific factors in vivo, even existing limitations. These improvements will enhance
long after transplantation. their utility in mechanistic studies, biomarker discovery,
Organoid transplantation is a promising approach for and therapeutic development, ultimately contributing to
PD treatment, offering the potential to replace lost DA better-targeted treatments for PD.
neurons and restore brain function. However, several Acknowledgments
challenges must be addressed, including poor graft
survival, lack of vascularization, immune rejection, and None.
risks of uncontrolled proliferation or tumorigenicity. 86-88
Ensuring functional integration of transplanted organoids Funding
into host neural circuits remains a key hurdle, as differences None.
in neuronal maturation and synaptic plasticity may affect
their efficacy. 78,89,90 Additionally, ethical and regulatory Conflict of interest
concerns regarding the safety and long-term monitoring of The authors declare they have no competing interests.
organoid-based therapies present further barriers to clinical
translation. Advancements in vascularized organoids, Author contributions
immune modulation strategies, and bioengineering are
crucial to overcoming these challenges and realizing the Conceptualization: Siyue Qin, Xinglong Wang
full therapeutic potential of organoid transplantation Writing-original draft: Siyue Qin
for PD. Writing-review & editing: All authors
5. Conclusion and perspectives Ethics approval and consent to participate
Not applicable.
Organoid technology has emerged as a powerful tool
in PD research, bridging the gap between traditional Consent for publication
models and the complexity of human pathology. Midbrain
organoids accurately mimic the cellular and structural Not applicable.
features of the human midbrain, enabling in-depth studies Availability of data
of PD mechanisms, including α-synuclein aggregation,
DA neuron loss, neuroinflammation, and mitochondrial Not applicable.
dysfunction. They have proven invaluable for drug
discovery, high-throughput screening, and regenerative References
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progress in organoid technology and bioengineering is doi: 10.1176/jnp.14.2.223
helping to address these issues. Further efforts are needed 2. Goetz CG. The history of parkinson’s disease: Early clinical
to refine organoid technology, including enhancing descriptions and neurological therapies. Cold Spring Harb
vascularization, incorporating microglia and astrocytes, Perspect Med. 2011;1(1):a008862.
and improving long-term culture conditions to better doi: 10.1101/cshperspect.a008862
mimic in vivo PD pathology. From a drug screening
perspective, while organoids offer a promising alternative 3. Sveinbjornsdottir S. The clinical symptoms of Parkinson’s
to traditional 2D cultures and animal models, challenges disease. J Neurochem. 2016;139 Suppl 1:318-324.
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Volume 1 Issue 2 (2025) 8 doi: 10.36922/OR025040006