Pericytes in Microvessels: From “Mural” Function to Brain and Retina Regeneration

Pericytes are branched cells located in the wall of capillary blood vessels that are found throughout the body, embedded within the microvascular basement membrane and wrapping endothelial cells, with which they establish a strong physical contact. Pericytes regulate angiogenesis, vessel stabilization, and contribute to the formation of both the blood-brain and blood-retina barriers by Angiopoietin-1/Tie-2, platelet derived growth factor (PDGF) and transforming growth factor (TGF) signaling pathways, regulating pericyte-endothelial cell communication. Human pericytes that have been cultured for a long period give rise to multilineage progenitor cells and exhibit mesenchymal stem cell (MSC) features. We focused our attention on the roles of pericytes in brain and ocular diseases. In particular, pericyte involvement in brain ischemia, brain tumors, diabetic retinopathy, and uveal melanoma is described. Several molecules, such as adenosine and nitric oxide, are responsible for pericyte shrinkage during ischemia-reperfusion. Anti-inflammatory molecules, such as IL-10, TGFβ, and MHC-II, which are increased in glioblastoma-activated pericytes, are responsible for tumor growth. As regards the eye, pericytes play a role not only in ocular vessel stabilization, but also as a stem cell niche that contributes to regenerative processes in diabetic retinopathy. Moreover, pericytes participate in melanoma cell extravasation and the genetic ablation of the PDGF receptor reduces the number of pericytes and aberrant tumor microvessel formation with important implications for therapy efficacy. Thanks to their MSC features, pericytes could be considered excellent candidates to promote nervous tissue repair and for regenerative medicine.

CARBON NANOTUBE RIBBON AND THREAD SUPPORT ATTACHMENT AND DIFFERENTIATION OF NEURAL STEM CELLS

Carbon nanotubes (CNTs) have properties that promise an exciting role in nervous tissue repair. CNTs are strong, extremely light weight, biocompatible and electrically conductive. A relatively novel form of CNT material, multiple strands of CNTs spun into thread, accentuates the linear geometry of CNTs while retaining electrical conductivity. We propose that CNT thread, which is strong, pliable and readily manipulated, has the potential to support longitudinal growth of nerves after injury, in nervous system prostheses. Towards understanding how CNT materials support nervous tissue regeneration, we examined the in vitro interactions between CNT materials and neural stem cell-containing neurospheres, prepared from newborn mouse cortices. Intact neurospheres attached to pieces of as-grown arrays of CNTs, CNT "ribbon" material pulled from the arrays, and CNT thread. Stem cells differentiated into both neurons and glia under these conditions. Processes and cells aligned with the longitudinal axis of the CNT materials, both with and without coatings. For comparisons, dissociated neurosphere cells were plated on CNT thread, polypropylene surgical suture thread and commercial carbon fibers. Initial cell attachment (within seconds) and attachment at 24 h was greater on CNT thread than on the other fiber types. Stem cells on CNT threads differentiated into neurons and astrocytes over several days, on all fibers. The presence of serum greatly aided the health and spreading of both neurons and astrocytes. These findings demonstrate that CNT materials, in particular the thread form, are viable preparations for neural cell attachment, outgrowth and differentiation.