The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells

Abstract

Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain.

Brain mesenchymal stem cells: The other stem cells of the brain?

“…Hence, the difficulty to obtain functional mature neurons by differentiating bone MSC can be explained both by their origin and by cell culture conditions which are far to provide the cues found in the brain microenvironment. Accordingly, recent experiments using brain derived MSCs instead of bone marrow MSCs, provide additional evidence on the potential of brain MSCs to transdifferentiate into neuronal cells at the clonal level and on the basis of stringent criteria [54] . A notable point is that these observations are made in vitro.…”

Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

“…8 Moreover, PCs of different organs, including the brain, have been reported to possess mesenchymal stem cell characteristics with the potential to differentiate in vitro into bone, cartilage, or adipose tissue. [9][10][11] The plasticity of PCs is underscored by reports, which suggested multipotent stem cell characteristics of CNS microvascular PCs. 12 With the increasing interest in the complex functions of PCs and mural cells, new questions arise as to how PCs may be affected by pathologic conditions of the CNS.…”

Amyloid‐beta 1‐40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro

“…It may thus be that the decreased activity of caspase 3/7 in response to monomer Aβ1‐40 seen in our study contributes to both the increased cell viability and the increased cell division. Finally, it is important to point out that cell cultures can never replicate a biological system and although pericyte proliferation does occur in the human brain (Fernandez‐Klett et al., 2013; Goritz et al., 2011; Matsushita et al., 2015; Paul et al., 2012), the conditions and rate in the brain are not comparable to the same in a Petri dish. Hence, we would like to stress that our cell model is useful foremost as a tool to demonstrate that differences in pericyte response to Aβ depend on both aggregation form and specie.…”

“…These cells are very dynamic and versatile. In their mature state, they play a key role in vessel stabilization and vessel permeability, but in response to changes in their environment, pericytes become activated and take part in events such as vascular remodelling, inflammation (Bergers & Song, 2005; Paul et al., 2012) and clearance of neurotoxic substances (including Aβ) (Zlokovic, 2008). Hence, loss of pericytes leads not only to deleterious events, such as impaired BBB or vessel leakage (Quaegebeur, Segura & Carmeliet, 2010), but could also underlie the accumulation of Aβ in the AD brain.…”