ePoster

CD200-based cell sorting generates homogeneous subpopulations of transplantable striatal neuroblasts

Cinta Gomis, F. J. Molina-Ruiz, P. Sanders, J. Abante, F. Londoño, G. Bombau, M. Galofré, V. Monforte, O. Varea, J. M. Canals
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Cinta Gomis, F. J. Molina-Ruiz, P. Sanders, J. Abante, F. Londoño, G. Bombau, M. Galofré, V. Monforte, O. Varea, J. M. Canals

Abstract

Cell replacement therapy (CRT) holds promise for restoring atrophied tissue in Huntington’s Disease (HD) by replenishing degenerating striatal projection neurons (SPNs). However, the heterogeneous cell compositions resulting from striatal differentiation protocols hinder clinical translation. Standardizing production procedures is essential to ensure the generation of defined and safe cell products. This study aims to devise a novel therapeutic approach for brain tissue regeneration in HD, ensuring the presence of specified SPN progenitors while excluding overly proliferative cell types.Here, we report the development of an immunomagnetic sorting pipeline enabling the selection of post-mitotic neuroblasts (NBs) derived from human pluripotent stem cells (hPSCs). We characterized the identity of the selected cell subpopulations and assessed their ability to generate striatal neurons in vitro. Moreover, we evaluated the survival, safety, and fate of these NBs upon transplantation into the striatum of immunosuppressed adult mice.CD200 emerged as a marker of post-mitotic NBs, facilitating consistent and high-yield enrichment of CD200high NBs through magnetic-associated cell sorting (MACS). The resulting cell compositions exhibit hallmark characteristics of SPN progenitors of the developing striatum, which differentiate into the target SPN-like neurons in vitro. Additionally, sorted NBs retain the expression of subpallial markers and survive for at least one month following transplantation. The proposed CD200-based selection significantly reduces the presence of proliferative cells in the intrastriatal grafts, thereby minimizing the risk of graft overgrowth in vivo.In conclusion, this work highlights the translational value of CD200-based cell sorting to meet quality and safety requirements for future CRT in HD.

Unique ID: fens-24/cd200-based-cell-sorting-generates-homogeneous-daaa8808