Neuroprotective effects of human bone marrow mesenchymal stem cells against cerebral ischemia are mediated in part by an anti-apoptotic mechanism

Transplantation of human bone marrow mesenchymal stem cells(hMSCs) stands as a potent stroke therapy, but its exact mechanism remains unknown. This study investigated the anti-apoptotic mechanisms by which hMSCs exert neuroprotective effects on cerebral ischemia. Primary mixed cultures of rat neurons and astrocytes were cultured and exposed to oxygen-glucose deprivation. A two-hour period of "reperfusion" in standard medium and normoxic conditions was allowed and immediately followed by hMSCs and/or Bcl-2 antibody treatment. Cell viability of primary rat neurons and astrocytes was determined by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide and trypan blue exclusion methods. hMSC survival and differentiation were characterized by immunocytochemistry, while the concentration of Bcl-2 in the supernatant was measured by enzyme-linked immunosorbent assay to reveal the secretory anti-apoptotic function of hMSCs. Cultured hMSCs expressed embryonic-like stem cell phenotypic markers CXCR4, Oct4, SSEA4, and Nanog, as well as immature neural phenotypic marker Nestin. Primary rat neurons and astrocytes were protected from oxygen-glucose deprivation by hMSCs, which was antagonized by the Bcl-2 antibody. However, Bcl-2 levels in the supernatants did not differ between hMSCand non-treated cells exposed to oxygen-glucose deprivation. Neuroprotective effects of hMSCs against cerebral ischemia were partially mediated by the anti-apoptotic mechanisms. However, further studies are warranted to fully elucidate this pathway.

Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping

There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood con- tains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en- hances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant＇s susceptibility to both neonatal and age-related diseases.

The role of DJ-1 in the oxidative stress cell death cascade after stroke

Oxidative stress is closely associated with secondary cell death in many disorders of the central nervous system including stroke, Parkinson＇s disease, Alzheimer＇s disease. Among many aber-rant oxidative stress-associated proteins, DJ-1 has been associated with the oxidative stress cell death cascade primarily in Parkinson＇s disease. Although principally expressed in the cytoplasm and nucleus, DJ-1 can be secreted into the serum under pathological condition. Recently, a close pathological association between DJ-I and oxidative stress in stroke has been implicated. To this end, we and others have demonstrated the important role of mitochondria in neuroprotection for stroke by demonstrating that the translocation of DJ-1 in the mitochondria could potentially mitigate mitochondrial injury. Here, we discuss our recent findings testing the hypothesis that DJ- 1 not only functions as a form of intracellular protection from oxidative stress, but that it also utilizes paracrine and/or autocrine cues in order to accomplish extracellular signaling between neighboring neuronal cells, resulting in neuroprotection. This article highlights recent evidence supporting the status of DJ-1 as key anti-oxidative stress therapeutic target for stroke.