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CXCL12-mediated guidance of migrating embryonic stem cell-derived neural progenitors transplanted into the hippocampus.

  • Nathaniel W Hartman
    ,
  • Joseph E Carpentino
    ,
  • Kristi LaMonica
    ,
  • Danielle Emille Mor
    ,
  • Janice R Naegele
    ,
  • Laura Grabel
  • Wesleyan University
Scholary Output:
Contribution to journal
Article
 Peer-review

Abstract

Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals.

Publication Information

Output type

Scholary Output:
Contribution to journal
Article
 Peer-review

Original language

English (US)

Journal (Volume, Issue Number)

PloS one (Volume 5, Issue 12)

Publication milestones

  • Published - 12/31/2010

Publication status

Published - 12/31/2010

ISSN

1932-6203

Publication IDs

  • ORCID: /0000-0003-3851-5010/work/84895547
  • PubMed: 21209827
  • Scopus: 79251506964

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Publication metrics

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SciVal
citations
29
Scopus
citations
30, opens in new tab
Fractional count
1
Fractional count
0.17
Fractional count
5
Fractional count
0.83
Fractional count
1
Fractional count
1
SciVal
FWCI
1.24
SciVal
Author count
5
SciVal
Paper percentile
82

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Citation count
30
Captures
49