Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact

Romy Sweda, Andre W. Phillips, Joel Marx, Michael V. Johnston, Mary Ann Wilson, Ali Fatemi

Research output: Research - peer-reviewArticle

Abstract

Glial-Restricted Precursors (GRPs) are tripotential progenitors that have been shown to exhibit beneficial effects in several preclinical models of neurological disorders, including neonatal brain injury. The mechanisms of action of these cells, however, require further study, as do clinically relevant questions such as timing and route of cell administration. Here, we explored the effects of GRPs on neonatal hypoxia-ischemia during acute and subacute stages, using an in vitro transwell co-culture system with organotypic brain slices exposed to oxygen-glucose deprivation (OGD). OGD-exposed slices that were then co-cultured with GRPs without direct cell contact had decreased tissue injury and cortical cell death, as evaluated by lactate dehydrogenase (LDH) release and propidium iodide (PI) staining. This effect was more pronounced when cells were added during the subacute phase of the injury. Furthermore, GRPs reduced the amount of glutamate in the slice supernatant and changed the proliferation pattern of endogenous progenitor cells in brain slices. In summary, we show that GRPs exert a neuroprotective effect on neonatal hypoxia-ischemia without the need for direct cell-cell contact, thus confirming the rising view that beneficial actions of stem cells are more likely attributable to trophic or immunomodulatory support rather than to long-term integration.

LanguageEnglish (US)
Pages975-985
Number of pages11
JournalStem Cells and Development
Volume25
Issue number13
DOIs
StatePublished - Jul 1 2016

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Neuroglia
Cell Death
Brain
Stem Cells
Ischemia
Oxygen
Glucose
Wounds and Injuries
Hypoxia
Propidium
Neuroprotective Agents
Coculture Techniques
Nervous System Diseases
L-Lactate Dehydrogenase
Brain Injuries
Glutamic Acid
Staining and Labeling
In Vitro Techniques

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact. / Sweda, Romy; Phillips, Andre W.; Marx, Joel; Johnston, Michael V.; Wilson, Mary Ann; Fatemi, Ali.

In: Stem Cells and Development, Vol. 25, No. 13, 01.07.2016, p. 975-985.

Research output: Research - peer-reviewArticle

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