Multipotent adult progenitor cells for XXXX in the preterm brain.

@entity1 @entity1545 @entity410 @entity17 @entity742 @entity2806 @entity63 @entity519 @entity393
BACKGROUND: Preterm @entity1 are at risk for @entity2806 . No therapy exists to treat this @entity1545 and subsequent long-term sequelae. We have previously shown in a well-established pre-clinical model of global @entity519 - @entity63 (HI) that mesenchymal stem cells are a promising candidate for the treatment of @entity2806 . In the current study, we investigated the neuroprotective capacity of multipotent adult progenitor cells (MAPC(  )), which are adherent bone marrow-derived cells of an earlier developmental stage than mesenchymal stem cells and exhibiting more potent anti-inflammatory and regenerative properties. METHODS: Instrumented preterm @entity742 fetuses were subjected to global @entity519 - @entity63 by 25  min of umbilical cord occlusion at a gestational age of 106 (term ~147) days. During a 7-day reperfusion period, vital parameters (e.g., blood pressure and heart rate; baroreceptor reflex) and (amplitude-integrated) electroencephalogram were recorded. At the end of the experiment, the preterm brain was studied by histology. RESULTS: Systemic administration of MAPC therapy reduced the number and duration of @entity410 and prevented @entity393 after global HI. In addition, MAPC  cells prevented HI-induced microglial proliferation in the preterm brain. These anti-inflammatory effects were associated with MAPC-induced prevention of @entity17 after global HI. Besides attenuation of the cerebral inflammatory response, our findings showed that MAPC  cells modulated the peripheral splenic inflammatory response, which has been implicated in the etiology of @entity63 in the preterm brain. CONCLUSIONS: In a pre-clinical animal model MAPC cell therapy improved the functional and structural outcome of the preterm brain after global HI. Future studies should establish the mechanism and long-term therapeutic effects of neuroprotection established by MAPC  cells in the developing preterm brain exposed to HI. Our study may form the basis for future clinical trials, which will evaluate whether MAPC therapy is capable of reducing neurological sequelae in preterm @entity1 with @entity2806 .
