Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders.

Abstract

A reduced number or dysfunction of inhibitory interneurons is a common contributor to neurodevelopmental disorders. Therefore, cell therapy using interneurons to replace or mitigate the effects of altered neuronal circuits is an attractive therapeutic avenue. To this end, more knowledge is needed about how human stem cell-derived GABAergic interneuron-like cells (hdINs) mature, integrate, and function over time in the host circuitry. Of particular importance in neurodevelopmental disorders is a better understanding of whether these processes in transplanted cells are affected by an evolving and maturing host brain. The present protocol describes a fast and highly efficient generation of hdINs from human embryonic stem cells based on the transgenic expression of the transcription factors Ascl1 and Dlx2. These neuronal precursors are transplanted unilaterally, after 7 days in vitro, to the hippocampus of neonatal 2-day-old mice. The transplanted neurons disperse in the ipsi- and contralateral hippocampus of a mouse model of cortical dysplasia-focal epilepsy syndrome and survive for up to 9 months after transplantation. This approach allows for investigating the cellular identity, integration, functionality, and therapeutic potential of transplanted interneurons over an extended time in developing healthy and diseased brains.

• Authors: Ana Gonzalez-Ramos, Kerstin Laurin, Fredrik Berglind, Marco Ledri, Merab Kokaia, My Andersson
• Journal: Journal of visualized experiments : JoVE (J Vis Exp) Issue 189 (11 11 2022) ISSN: 1940-087X [Electronic] United States
• PMID: 36440838 (Publication Type: Journal Article, Video-Audio Media, Research Support, Non-U.S. Gov't)

Topics

• Humans
• Animals
• Mice
• GABAergic Neurons
• Interneurons (physiology)
• Stem Cells
• Hippocampus
• Neurodevelopmental Disorders