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Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.
Stem Cells Transl Med 2013; 2(12):953-60SC

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 of MWM trials, 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.

Authors+Show Affiliations

Departments of Pediatric Surgery and.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24191266

Citation

Bedi, Supinder S., et al. "Intravenous Multipotent Adult Progenitor Cell Therapy Attenuates Activated Microglial/macrophage Response and Improves Spatial Learning After Traumatic Brain Injury." Stem Cells Translational Medicine, vol. 2, no. 12, 2013, pp. 953-60.
Bedi SS, Hetz R, Thomas C, et al. Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury. Stem Cells Transl Med. 2013;2(12):953-60.
Bedi, S. S., Hetz, R., Thomas, C., Smith, P., Olsen, A. B., Williams, S., ... Cox, C. S. (2013). Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury. Stem Cells Translational Medicine, 2(12), pp. 953-60. doi:10.5966/sctm.2013-0100.
Bedi SS, et al. Intravenous Multipotent Adult Progenitor Cell Therapy Attenuates Activated Microglial/macrophage Response and Improves Spatial Learning After Traumatic Brain Injury. Stem Cells Transl Med. 2013;2(12):953-60. PubMed PMID: 24191266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury. AU - Bedi,Supinder S, AU - Hetz,Robert, AU - Thomas,Chelsea, AU - Smith,Philippa, AU - Olsen,Alex B, AU - Williams,Stephen, AU - Xue,Hasen, AU - Aroom,Kevin, AU - Uray,Karen, AU - Hamilton,Jason, AU - Mays,Robert W, AU - Cox,Charles S,Jr Y1 - 2013/11/04/ PY - 2013/11/6/entrez PY - 2013/11/6/pubmed PY - 2014/1/17/medline KW - Adult stem cells KW - Neuroimmune KW - Rat model KW - Stem/progenitor cell SP - 953 EP - 60 JF - Stem cells translational medicine JO - Stem Cells Transl Med VL - 2 IS - 12 N2 - 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 of MWM trials, 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. SN - 2157-6564 UR - https://www.unboundmedicine.com/medline/citation/24191266/Intravenous_multipotent_adult_progenitor_cell_therapy_attenuates_activated_microglial/macrophage_response_and_improves_spatial_learning_after_traumatic_brain_injury_ L2 - https://doi.org/10.5966/sctm.2013-0100 DB - PRIME DP - Unbound Medicine ER -