Introduction: It is hypothesized that administration of stromal/stem cells isolated from the adipose tissue (ASCs) and umbilical cord (HUCPVCs) can ameliorate the injured central nervous system (CNS). It is still not clear, however, whether they have similar or opposite effects on primary cultures of neuronal populations. The objective of the present work was to determine if ASCs and HUCPVCs preferentially act, or not, on specific cell populations within the CNS. Methods: Primary cultures of hippocampal neurons were exposed to ASCs and HUCPVCs conditioned media (CM) (obtained 24, 48, 72 and 96 hours after three days of culture) for one week. Results: Cell viability experiments (MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2H tetrazolium) test) revealed that CM obtained from both cell populations at all time points did not cause any deleterious effects on neuronal cells. In fact, it was determined that whenever the ASCs CM were supplemented with basic fibroblast growth factor (bFGF) and B27, there was a significant increase in the metabolic viability and neuronal cell density of the cultures. On the other hand, in the absence of CM supplementation, it was the HUCPVCs secretome that had the highest impact on the metabolic viability and cell density. In an attempt to unveil which factors could be involved in the observed effects, a screening for the presence of bFGF, nerve growth factor (NGF), stem cell factor (SCF), hepatocyte growth factors (HGF) and vascular endothelial growth factor (VEGF) in the CM was performed. Results revealed the presence of all these factors in ASCs CM, except bFGF; in contrast, in HUCPVCs CM it was only possible to detect robust NGF expression. Conclusions: Overall, the results confirm important differences on the secretome of ASCs and HUCPVCs, which lead to distinct effects on the metabolic viability and neuronal cell densities in primary cultures of hippocampal neurons; however, the factor(s) that promote the stronger effect of the HUCPVCs CM in neuronal survival is(are) still to be identified.

Transthyretin (TTR) binds Aβ peptide, preventing its deposition and toxicity. TTR is decreased in Alzheimer’s disease (AD) patients. Additionally, AD transgenic mice with only one copy of the TTR gene show increased brain and plasma Aβ levels when compared to AD mice with both copies of the gene, suggesting TTR involvement in brain Aβ efflux and/or peripheral clearance. Here we showed that TTR promotes Aβ internalization and efflux in a human cerebral microvascular endothelial cell line, hCMEC/D3. TTR also stimulated brain-to-blood but not blood-to-brain Aβ permeability in hCMEC/D3, suggesting that TTR interacts directly with Aβ at the blood-brain-barrier. We also observed that TTR crosses the monolayer of cells only in the brain-to-blood direction, as confirmed by in vivo studies, suggesting that TTR can transport Aβ from, but not into the brain. Furthermore, TTR increased Aβ internalization by SAHep cells and by primary hepatocytes from TTR+/+ mice when compared to TTR−/− animals. We propose that TTR-mediated Aβ clearance is through LRP1, as lower receptor expression was found in brains and livers of TTR−/− mice and in cells incubated without TTR. Our results suggest that TTR acts as a carrier of Aβ at the blood-brain-barrier and liver, using LRP1.

Transplantation of bone marrow mesenchymal stem cells (BM‐MSCs) has been shown to ameliorate the injured central nervous system (CNS). Although these effects were initially attributed to the putative differentiation of MSCs towards the neural lineage, it is now known that most of them are mediated by the secretome. Up to now most in vitro reports have dealt with the effects of the secretome on neural stem cells and their differentiation. Consequently, there is a lack of information regarding the role of the secretome on the viability and survival of pre‐existent matured differentiated cell populations. Moreover, it is also not known how the time points of conditioned media (CM) collection affect such parameters. In the present study, primary cultures of hippocampal neurons and glial cells were incubated with CM obtained from MSCs. To determine how the temporal profiles of CM collection impact on post‐natal neurons and glial cells, we collected MSCs CM at 24, 48, 72 and 96 h of conditioning. MTS test revealed that for the hippocampal cultures the incubation with CM increased cell viability for all time points, with significant increases in the percentage of neurons in culture incubated with CM 24 h. For glial cells only the later time point of CM collection (96 h) increased cell viability. Fluorescence microscopy observations also revealed that CM 48 h and 72 h increased astrocytes percentages, while CM 24 h decreased microglial cell and oligodendrocytes values. These results revealed that post‐natal neuronal and glial cells respond differently to MSCs CM; moreover, there are specific temporal variations in the composition of the CM of MSCs collected at different time points that trigger different effects on mature neurons and the distinct glial cell populations (astrocytes, oligodendrocytes and microglial cells). Copyright © 2011 John Wiley & Sons, Ltd.

Different authors described that transthyretin (TTR) is decreased in the cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients and thus TTR is a potential CSF biomarker in AD. However, descriptions of what happens to TTR in plasma of these patients are lacking in the literature. We investigated TTR levels in plasma samples from 55 patients with mild-cognitive impairment (MCI), 56 patients with AD and 41 non-demented controls, and found that TTR is decreased in both MCI and AD groups, suggesting that TTR might be used for staging early AD. In MCI and AD groups, women showed significantly lower plasma TTR levels when compared to MCI and AD men, respectively, and to women control group. In the AD women group, TTR levels correlated with disease stage, reflecting disease severity. Although MCI and AD men groups presented TTR levels lower than men in the control group, the difference was not statistically significant. Genetic analysis for ApoE revealed no relationship between TTR levels and the presence of the ε4 allele, for both men and women, in both patient groups. Importantly, we assessed thyroxine binding to TTR in plasma and found, in both MCI and AD groups, that TTR had reduced capacity to carry the hormone. Finally, we measured plasma estradiol levels in women and showed a reduction in both groups. Thus, this study prompts TTR as an early plasma biomarker in AD indicating that disease modulation by TTR is gender dependent; this study provides hypotheses into the mechanisms involved.