Objective: We propose that the striatal transplantation of 3D-neural organoids of controlled cell size and cell content, named “Controlled Neural Organoids” (CNOs), could circumvent the limitations of current cell therapy and allow functional recovery in Parkinson’s disease (PD).

Background: A major impetus for research in PD is centered on cell therapy strategies that aim at replacing the dysfunctional or dying neuronal cell populations. In the past decade, pluripotent stem cells have provided unprecedented access to various human cell types, especially to central nervous system neurons. The availability of patient-specific cell lines associated with the development of highly efficient protocols to in vitro generate specific neuronal cells is an important step in overcoming the ethical and logistical challenges associated with the use of embryonic stem cells. However, mature neuronal transplantation leads to poor survival due to their detachment sensitivity and the fragility of neuritic extensions. Similarly, the transplantation of neuronal precursors does not allow in situ tight control of the neuronal identity and carries a tumor risk.

Methods: CNOs were generated through cell capsules technology developed in the lab associated with differentiation protocol of dopaminergic neurons (DN) from human pluripotent stem cells. Following the neuronal transplantation in immunocompromised hemiparkinsonian rats (6-OHDA), motor functions were evaluated by stepping test, cylinder test and amphetamine-induced rotations. CNOs characterization was carried out by immunostaining. In this study, we compared the therapeutic efficacy of 3D-neural organoids versus individual neurons transplantation.

Results: From eight weeks onwards after the transplantation, CNOs allowed functional recovery associated with tyrosine hydroxylase positive neurons into the graft whereas the transplantation of dopaminergic individual neurons did not induce any effect.

Conclusions: Our CNOs constitute more efficient and safer cell therapy products than individual neurons. Pending further validation, this innovative cell therapy approach for the treatment of PD could become a real alternative to drug-based symptomatologic treatments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/controlled-neural-organoids-grafting-promotes-functional-recovery-in-experimental-parkinsonism/