Background and Purpose Pentraxin 3 (PTX3) is released upon inflammatory responses in many organs. However, roles of PTX3 in brain are still mostly unknown. Here we asked whether and how PTX3 contributes to blood-brain barrier (BBB) dysfunction during the acute phase of ischemic stroke. Methods In vivo, spontaneously hypertensive rats were subjected to focal cerebral ischemia by transient middle cerebral artery occlusion. At day 3, brains were analyzed to evaluate the cellular origin of PTX3 expression. Correlations with BBB breakdown were assessed by IgG staining. In vitro, rat primary astrocytes and rat brain endothelial RBE.4 cells were cultured to study the role of astrocyte-derived PTX3 on VEGF-mediated endothelial permeability. Results During the acute phase of stroke, reactive astrocytes in the peri-infarct area expressed PTX3. There was negative correlation between gradients of IgG leakage and PTX3-positive astrocytes. Cell culture experiments showed that astrocyte-conditioned media increased levels of tight junction proteins and reduced endothelial permeability under normal conditions. Removing PTX3 from astrocyte-conditioned media by immunoprecipitation increased endothelial permeability. PTX3 strongly bound VEGF in vitro and was able to decrease VEGF-induced endothelial permeability. Conclusions Astrocytes in peri-infarct areas upregulate PTX3 which may support BBB integrity by regulating VEGF-related mechanisms. This response in astrocytes may comprise a compensatory mechanism for maintaining BBB function after ischemic stroke.

Mesenchymal stem cells (MSCs) are multipotent cells that have the capability of differentiating into adipogenic, osteogenic, chondrogenic, and neural cells. With these multiple capabilities, MSCs have been highly regarded as effective transplantable cell source for regenerative medicine. A large bank of these cells can be found in several regions of the human umbilical cord (hUC) including the umbilical cord lining, the subendothelial layer, the perivascular zone, and most importantly in Wharton’s jelly (WJ). These cells, all umbilical cord-derived MSCs, are very durable, have large loading capacities, and are considered ethical to harvest because the umbilical cord is often considered a waste. These logistical advantages make WJ as appealing source of stem cells for transplant therapy. In particular, WJ is a predominantly good source of cells because MSCs in WJ (WJ-MSC) are maintained in a very early embryological phase and therefore have retained some of the primitive stemness properties. WJ-MSCs can easily differentiate into a plethora of cell types leading to a variety of applications. In addition, WJ-MSCs are slightly easier to harvest compared to other MSCs (such as bone marrow-derived MSCs). The fascinating stemness properties and therapeutic potential of WJ-MSCs provide great promise in many aspects of regenerative medicine and should be considered for further investigations as safe and effective donor cells for transplantation therapy in many debilitating disorders, which are discussed here. We previously reviewed WJ-MSCs therapeutic potential [1] and now provide an update on their recent preclinical and clinical applications.