The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells

TLDR

Perivascular niches in adult tissues contain pericytes that express mesenchymal markers and can differentiate into mesodermal lineages, suggesting a potential source of multipotent stem cells. The study aimed to isolate, purify, and characterize a previously unrecognized progenitor population from the ventricular wall and neocortex of the adult human brain. Researchers isolated and purified these progenitors from two brain regions, then performed in vitro and clonal assays to assess marker expression and lineage potential. The isolated cells co‑express mesenchymal stem cell and pericyte markers, lack glial/neural/hematopoietic markers, and demonstrate multilineage differentiation into mesodermal and neuroectodermal lineages, with long‑term proliferation, karyotype stability, and maintained multipotency.

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.