Organoid-to-organoid transplantation and pro-neurogenic treatment promote graft integration and neuronal repair in a human ischemic model
- 1University of Liege, Belgium
Abstract
Neuronal loss resulting from brain injury and neurodegenerative diseases currently lacks effective regenerative therapies. While neurogenic compounds and cell transplantation hold promise, clinical translation is hindered by poor graft integration and limited cell survival. Here, we developed a novel organoid-to-organoid transplantation model using human pluripotent stem cell-derived cortical organoids (hCOs) to evaluate a dual cell transplantation and pro-neurogenic strategy for brain repair. We demonstrate that pro-neurogenic treatment with ER272 stimulates early-stage hCO growth and enhances neurogenesis through a PKC- and Notch-dependent pathway. Mechanistically, ER272 upregulates genes associated with extracellular matrix, cell adhesion and growth factor signaling. Notably, combining early-stage hCO transplantation with ER272 treatment significantly enhanced graft integration and improved neuronal repair in an ischemic-like model of late-stage host hCOs. This novel human organoid-to-organoid platform offers a robust translational tool to test regenerative therapies and highlight the potential of combining cell transplantation with pro-neurogenic stimulation for the treatment of neurological conditions associated with neuronal loss.
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BibTeX
@misc{gomezoliva2026organoidtoorganoid,
title = {{Organoid-to-organoid transplantation and pro-neurogenic treatment promote graft integration and neuronal repair in a human ischemic model}},
author = {R. Gomez-Oliva and S. Helgueta and N. Alonso-Galeron and A. Cambier and F. Ghanavatinejad and G. Masset and L. Collin and P. Nunez-Abades and R. Hernandez-Galan and C. Castro and I. Espuny Camacho},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.25.754353},
url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754353v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Organoid-to-organoid transplantation and pro-neurogenic treatment promote graft integration and neuronal repair in a human ischemic model
AU - R. Gomez-Oliva
AU - S. Helgueta
AU - N. Alonso-Galeron
AU - A. Cambier
AU - F. Ghanavatinejad
AU - G. Masset
AU - L. Collin
AU - P. Nunez-Abades
AU - R. Hernandez-Galan
AU - C. Castro
AU - I. Espuny Camacho
PY - 2026
DA - 2026/09/25
PB - bioRxiv
DO - 10.64898/2026.09.25.754353
UR - https://www.biorxiv.org/content/10.64898/2026.09.25.754353v1
AB - Neuronal loss resulting from brain injury and neurodegenerative diseases currently lacks effective regenerative therapies. While neurogenic compounds and cell transplantation hold promise, clinical translation is hindered by poor graft integration and limited cell survival. Here, we developed a novel organoid-to-organoid transplantation model using human pluripotent stem cell-derived cortical organoids (hCOs) to evaluate a dual cell transplantation and pro-neurogenic strategy for brain repair. We demonstrate that pro-neurogenic treatment with ER272 stimulates early-stage hCO growth and enhances neurogenesis through a PKC- and Notch-dependent pathway. Mechanistically, ER272 upregulates genes associated with extracellular matrix, cell adhesion and growth factor signaling. Notably, combining early-stage hCO transplantation with ER272 treatment significantly enhanced graft integration and improved neuronal repair in an ischemic-like model of late-stage host hCOs. This novel human organoid-to-organoid platform offers a robust translational tool to test regenerative therapies and highlight the potential of combining cell transplantation with pro-neurogenic stimulation for the treatment of neurological conditions associated with neuronal loss.
ER -