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

Gonzalez-Ramos, Ana LU ; Laurin, Kerstin LU orcid ; Berglind, Fredrik LU ; Ledri, Marco LU ; Kokaia, Merab LU and Andersson, My LU orcid (2022) In Journal of visualized experiments : JoVE
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of visualized experiments : JoVE
issue
189
publisher
JoVE
external identifiers
  • scopus:85142859719
  • pmid:36440838
ISSN
1940-087X
DOI
10.3791/64272
language
English
LU publication?
yes
id
e0ae973e-aeb1-40b0-a239-a0af56a1e53f
date added to LUP
2022-12-23 11:05:52
date last changed
2024-04-16 18:39:48
@article{e0ae973e-aeb1-40b0-a239-a0af56a1e53f,
  abstract     = {{<p>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.</p>}},
  author       = {{Gonzalez-Ramos, Ana and Laurin, Kerstin and Berglind, Fredrik and Ledri, Marco and Kokaia, Merab and Andersson, My}},
  issn         = {{1940-087X}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{189}},
  publisher    = {{JoVE}},
  series       = {{Journal of visualized experiments : JoVE}},
  title        = {{Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders}},
  url          = {{http://dx.doi.org/10.3791/64272}},
  doi          = {{10.3791/64272}},
  year         = {{2022}},
}