chemogenetic-regulation-reprogrammed-stem-cell-derived-precursor

Chemogenetic Regulation in Reprogrammed Stem Cell-derived Precursor Cells in Treating Neurodegenerative Diseases

The integration of designer receptors exclusively activated by designer drugs (DREADD) with stem cell-based therapies presents an advanced strategy for ...

Xuanwu Hospital Capital Medical University

 Parkinson's disease (PD) is a prevalent neurodegenerative disorder that is characterized by degeneration of dopaminergic neurons (DA) at the substantia nigra pas compacta (SNpc). Cell therapy has been proposed as a potential treatment option for PD, with the aim of replenishing the lost DA neurons and restoring motor function. Fetal ventral mesencephalon tissues (fVM) and stem cell-derived DA precursors cultured in 2-dimentional (2-D) culture conditions have shown promising therapeutic outcomes in animal models and clinical trials. Recently, human induced pluripotent stem cells (hiPSC)-derived human midbrain organoids (hMOs) cultured in 3-dimentional (3-D) culture conditions have emerged as a novel source of graft that combines the strengths of fVM tissues and 2-D DA cells.  3-D hMOs were induced from three distinct hiPSC lines. hMOs at various stages of differentiation were transplanted as tissue pieces into the striatum of naïve immunodeficient mouse brains, with the aim of identifying the most suitable stage of hMOs for cellular therapy. The hMOs at Day 15 were determined to be the most appropriate stage and were transplanted into a PD mouse model to assess cell survival, differentiation, and axonal innervation . Behavioral tests were conducted to evaluate functional restoration following hMO treatment and to compare the therapeutic effects between 2-D and 3-D cultures. Rabies virus were introduced to identify the host presynaptic input onto the transplanted cells.  hMOs showed a relatively homogeneous cell composition, mostly consisting of dopaminergic cells of midbrain lineage. Analysis conducted 12 weeks post-transplantation of day 15 hMOs revealed that 14.11% of the engrafted cells expressed TH+ and over 90% of these cells were co-labeled with GIRK2+, indicating the survival and maturation of A9 mDA neurons in the striatum of PD mice. Transplantation of hMOs led to a reversal of motor function and establishment of bidirectional connections with natural brain target regions, without any incidence of tumor formation or graft overgrowth.  The findings of this study highlight the potential of hMOs as safe and efficacious donor graft sources for cell therapy to treat PD.

Human iPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson's disease.

Acute effect of twice-daily 15 mA transcranial alternating current stimulation on treatment-resistant depression: a case series study.

Emotion processing is an integral part of everyone's life. The basic neural circuits involved in emotion perception are becoming clear, though the emotion's cognitive processing remains under investigation. Utilizing the stereo-electroencephalograph with high temporal-spatial resolution, this study aims to decipher the neural pathway responsible for discriminating low-arousal and high-arousal emotions. This study involves 19 patients with pharmacologically resistant epilepsy who participate in a delayed match/mismatch sample task designed to separately assess their ability to discriminate between low-arousal and high-arousal emotions. Three groups of 11 brain subregions, with dominant lateralization, compose a network, which is identified as responsible for discriminating arousal-dependent emotions. The connection of these subregions, leading by the left insula and right middle temporal gyrus, defines the pathways for discriminating emotions with different arousals. Further, the separated network patterns related to emotional discrimination are face-independent. Overall, the left insula and the right middle temporal gyrus emerge as core components in the network, which plays key roles in the dynamic course for discriminating low- and high-arousal emotions in the human brain.

Article	Year
Human iPSC-derived midbrain organoids functionally integrate into striatum circuits and restore motor function in a mouse model of Parkinson's disease. Theranostics\| PubMed ID: 37215566	2023
Acute effect of twice-daily 15 mA transcranial alternating current stimulation on treatment-resistant depression: a case series study. General psychiatry\| PubMed ID: 38028814	2023
Left Insula and Right Middle Temporal Gyrus Dominate Cortical Network Discriminating Arousal-dependent Emotions. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 39823533	2025

Na Pan

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