Speaker
Description
"Huntington’s disease (HD) is a devastating neurodegenerative disorder characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum, leading to severe motor, cognitive, and psychiatric impairments. As no disease-modifying treatments are currently available, cell replacement therapy has emerged as a potential promising approach to restore striatal function.
From this perspective, developing an optimized differentiation protocol is key to generating the most effective cell product from human embryonic stem cells (hESCs), capable of functionally replacing degenerated striatal neurons upon transplantation. Equally crucial is ensuring their integration into host circuits to restore lost connections and regain function.
In this study, we employed multiple approaches to explore the characteristics and behavior of second generation hESC-derived striatal neurons transplanted into the striatum of an HD rat model.
Through snRNA-seq analysis, we identified the specific cellular composition of our transplants, uncovering a diverse mix of neuronal and non-neuronal populations typically found in the striatum, including MSNs, interneurons, and astrocytes.
To study the graft activity and its integration into host circuitries, we further engineered the cells for chemogenetic modulation to induce detectable phenotypic changes in behavioral tests. The obtained Bi-DREADD cell lines responded properly to different ligands in vitro. We also demonstrated that by 6 months post transplantation, grafted cells are functionally active and capable of responding to external stimuli.
Collectively, these findings highlight the robustness of our transplant, offering a wealth of new insights into the therapeutic potential of stem cell-derived cell replacement approaches for HD."
| Author(s) | Linda Scaramuzza*, Marta Ribodino*, Christian Cassarino, Roberta Parolisi, Gabriela Gomez-Gonzalez, Greta Galeotti, Marta Morrocchi, Simone Maestri, Dario Besusso, Annalisa Buffo, Elena Cattaneo |
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| Affiliation(s) | University of Milan and Istituto Nazionale Genetica Molecolare, Neuroscience Institute Cavalieri Ottolenghi- University of Turin,University of Milan and Istituto Nazionale Genetica Molecolare, Neuroscience Institute Cavalieri Ottolenghi- University of Turin, Neuroscience Institute Cavalieri Ottolenghi- University of Turin, Human technopole,University of Milan and Istituto Nazionale Genetica Molecolare,University of Milan and Istituto Nazionale Genetica Molecolare, University of Milan and Istituto Nazionale Genetica Molecolare, Neuroscience Institute Cavalieri Ottolenghi- University of Turin, University of Milan and Istituto Nazionale Genetica Molecolare |
