Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury

Supinder S. Bedi, Robert Hetz, Chelsea Thomas, Philippa Smith, Alex B. Olsen, Stephen Williams, Hasen Xue, Kevin Aroom, Karen Uray, Jason Hamilton, Robert W. Mays, Charles S. Cox

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI). We tested four groups at 120 days after TBI: sham (uninjured), injured but not treated (CCI), and injured and treated with one of two concentrations of MAPCs, either 2 million cells per kilogram (CCI-2) or 10 million cells per kilogram (CCI-10). CCI-10 rats showed significant improvement in left hind limb deficit on the balance beam. On the fifth day ofMWMtrials, CCI-10 animals showed a significant decrease in both latency to platform and distance traveled compared with CCI. Probe trials revealed a significant decrease in proximity measure in CCI-10 compared with CCI, suggesting improved memory retrieval. Neuroinflammation was quantified by enumerating activated microglia in the ipsilateral hippocampus. We observed a significant decrease in the number of activated microglia in the dentate gyrus in CCI-10 compared with CCI. Our results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvements in spatial learning as well as attenuation of neuroinflammation.

Original languageEnglish (US)
Pages (from-to)953-960
Number of pages8
JournalStem Cells Translational Medicine
Volume2
Issue number12
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Adult stem cells
  • Neuroimmune
  • Rat model
  • Stem/progenitor cell

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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