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Transsynaptic tracing and its emerging use to assess graftreconstructed neural circuits

Adler, Andrew LU ; Björklund, Anders LU orcid and Parmar, Malin LU orcid (2020) In Stem Cells 38(6). p.716-726
Abstract
Fetal neural progenitor grafts have been evaluated in preclinical animal models of spinal cord injury and Parkinson’s disease for decades, but the initial reliance on primary tissue as a cell source limited the scale of their clinical translatability. With the development of robust methods to differentiate human pluripotent stem cells to specific neural subtypes, cell replacement therapy holds renewed promise to treat a variety of neurodegenerative diseases and injuries at scale. As these cell sources are evaluated in preclinical models, new transsynaptic tracing methods are making it possible to study the connectivity between host and graft neurons with greater speed and detail than was previously possible. To date, these studies have... (More)
Fetal neural progenitor grafts have been evaluated in preclinical animal models of spinal cord injury and Parkinson’s disease for decades, but the initial reliance on primary tissue as a cell source limited the scale of their clinical translatability. With the development of robust methods to differentiate human pluripotent stem cells to specific neural subtypes, cell replacement therapy holds renewed promise to treat a variety of neurodegenerative diseases and injuries at scale. As these cell sources are evaluated in preclinical models, new transsynaptic tracing methods are making it possible to study the connectivity between host and graft neurons with greater speed and detail than was previously possible. To date, these studies have revealed that widespread, long-lasting, and anatomically-appropriate synaptic contacts are established between host and graft neurons, as well as new aspects of host-graft connectivity which may be relevant to clinical cell replacement therapy. It is not yet clear, however, whether the synaptic connectivity between graft and host neurons is as celltype specific as it is in the endogenous nervous system, or whether that connectivity is responsible for the functional efficacy of cell replacement therapy. Here, we review evidence suggesting that the new contacts established between host and graft neurons
may indeed be cell-type specific, and how transsynaptic tracing can be used in
the future to further elucidate the mechanisms of graft-mediated functional recovery in spinal cord injury and Parkinson’s disease. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cells
volume
38
issue
6
pages
11 pages
publisher
Oxford University Press
external identifiers
  • pmid:32101353
  • scopus:85081628734
ISSN
1549-4918
DOI
10.1002/stem.3166
language
English
LU publication?
yes
id
ea6e1f25-5fa0-4e9e-aab6-2c7b0a08169a
date added to LUP
2020-03-05 11:42:00
date last changed
2023-02-26 21:21:04
@article{ea6e1f25-5fa0-4e9e-aab6-2c7b0a08169a,
  abstract     = {{Fetal neural progenitor grafts have been evaluated in preclinical animal models of spinal cord injury and Parkinson’s disease for decades, but the initial reliance on primary tissue as a cell source limited the scale of their clinical translatability. With the development of robust methods to differentiate human pluripotent stem cells to specific neural subtypes, cell replacement therapy holds renewed promise to treat a variety of neurodegenerative diseases and injuries at scale. As these cell sources are evaluated in preclinical models, new transsynaptic tracing methods are making it possible to study the connectivity between host and graft neurons with greater speed and detail than was previously possible. To date, these studies have revealed that widespread, long-lasting, and anatomically-appropriate synaptic contacts are established between host and graft neurons, as well as new aspects of host-graft connectivity which may be relevant to clinical cell replacement therapy. It is not yet clear, however, whether the synaptic connectivity between graft and host neurons is as celltype specific as it is in the endogenous nervous system, or whether that connectivity is responsible for the functional efficacy of cell replacement therapy. Here, we review evidence suggesting that the new contacts established between host and graft neurons<br/>may indeed be cell-type specific, and how transsynaptic tracing can be used in<br/>the future to further elucidate the mechanisms of graft-mediated functional recovery in spinal cord injury and Parkinson’s disease.}},
  author       = {{Adler, Andrew and Björklund, Anders and Parmar, Malin}},
  issn         = {{1549-4918}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{716--726}},
  publisher    = {{Oxford University Press}},
  series       = {{Stem Cells}},
  title        = {{Transsynaptic tracing and its emerging use to assess graftreconstructed neural circuits}},
  url          = {{https://lup.lub.lu.se/search/files/76898618/publication_in_stem_cells.pdf}},
  doi          = {{10.1002/stem.3166}},
  volume       = {{38}},
  year         = {{2020}},
}