Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population.
J Neuroinflammation
; 9: 228, 2012 Sep 28.
Article
en En
| MEDLINE
| ID: mdl-23020860
ABSTRACT
INTRODUCTION:
We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population.METHODS:
C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4(+)/CD25(+)/FOXP3(+) T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86(+) M1 and CD206(+) M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPCsplenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation.RESULTS:
Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPCsplenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis.CONCLUSIONS:
The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC-mediated neuroprotection.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lesiones Encefálicas
/
Microglía
/
Células Madre Multipotentes
/
Células Madre Adultas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Neuroinflammation
Asunto de la revista:
NEUROLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos