Newly Identified Brain MSCs Differentiate Along Mesenchymal, Neuronal Lineages
Discovery may facilitate brain repair research and the development of new therapeutic approaches.
Scientists have identified and isolated a previously unidentified population of mesenchymal stem cells (MSCs) that surround blood vessels in the adult brain and which they say could feasibly be exploited for repairing damaged or diseased brain tissue. A team led by Patrik Brundin, M.D., and colleagues at Lund University’s Wallenberg Neuroscience Center, isolated, purified, and characterized the perivascular stem cells from the ventricular wall and neocortex of brain biopsies.
Patrik Brundin, M.D.,et al. claim the isolated MSCs differs from previously described human neural stem cells, as they are highly positive for both pericyte and MSC markers and negative for hematopoietic, endothelial, microglial, and glial markers. Indeed, while the cells exhibited a mesenchymal phenotype and could be differentiated into osteoblasts, chondrocytes, and adipocytes, they could also be epigenetically induced to differentiate along glial and neuronal lineages. “This has not been reported for a human brain-derived progenitor cell before,” the team remarks. Encouragingly, the perivascular MSCs could be propagated efficiently over the long term as adherent cultures, and the cells demonstrated clonality and retained a stable karyotype and full differentiation capacity following extensive proliferation.
Interestingly, the investigators add, the findings tie in with recent studies suggesting that MSCs in vivo may reside in the perivascular niche and might actually represent a subclass of pericyte. While the team further admits that the function of dual phenotypic stem cells in vivo is unknown, they suggest further studies will help determine whether they can be exploited for therapeutic applications. Dr. Brundin and colleagues report their findings in PLoS One in a paper titled “The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells.”
The investigators claim the newly identified perivascular MSCs clearly aren’t the same as previously described neural stem cells. In addition to their expression of perivasular and mesenchymal phenotypes and capacity for both neuroectodermal and mesodermal differentiation, clonal perivascualr MSCs derived from the adult human brain don’t express mRNA for neural progenitors or exhibit neuronal markers when proliferating.
Their discovery is of particular note as tissue-specific differentiation capacity of pericytes has previously been observed under pathological conditions, the authors point out. This includes pericyte differentiation into adipocytes during fat tissue injury or, dependent on their location, into chondroblasts, bone, myoblasts, or Leydig cells. And studies in animal models have separately demonstrated that pericytes can contribute to spinal cord repair by differentiation into astrocytes. “Our findings support previous data in primates and rodents that indicate the possible derivation of neurons from pericytes in the central nervous system,” they write.
The new cell type will hopefully lead to a better understanding of the brain’s own repair mechanisms,comments lead author Gesine Paul-Visse, Ph.D. “The results contribute to better understanding of how brain cell plasticity works and opens up new opportunities to exploit these very features. Ultimately the goal is to strengthen these mechanisms and develop new treatments that can repair the diseased brain.”