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The adult human brain harbors multipotent perivascular mesenchymal stem cells.
PLoS One 2012; 7(4):e35577Plos

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.

Authors+Show Affiliations

Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden. gesine.paul@med.lu.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22523602

Citation

Paul, Gesine, et al. "The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells." PloS One, vol. 7, no. 4, 2012, pp. e35577.
Paul G, Özen I, Christophersen NS, et al. The adult human brain harbors multipotent perivascular mesenchymal stem cells. PLoS ONE. 2012;7(4):e35577.
Paul, G., Özen, I., Christophersen, N. S., Reinbothe, T., Bengzon, J., Visse, E., ... Brundin, P. (2012). The adult human brain harbors multipotent perivascular mesenchymal stem cells. PloS One, 7(4), pp. e35577. doi:10.1371/journal.pone.0035577.
Paul G, et al. The Adult Human Brain Harbors Multipotent Perivascular Mesenchymal Stem Cells. PLoS ONE. 2012;7(4):e35577. PubMed PMID: 22523602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The adult human brain harbors multipotent perivascular mesenchymal stem cells. AU - Paul,Gesine, AU - Özen,Ilknur, AU - Christophersen,Nicolaj S, AU - Reinbothe,Thomas, AU - Bengzon,Johan, AU - Visse,Edward, AU - Jansson,Katarina, AU - Dannaeus,Karin, AU - Henriques-Oliveira,Catarina, AU - Roybon,Laurent, AU - Anisimov,Sergey V, AU - Renström,Erik, AU - Svensson,Mikael, AU - Haegerstrand,Anders, AU - Brundin,Patrik, Y1 - 2012/04/16/ PY - 2011/06/21/received PY - 2012/03/20/accepted PY - 2012/4/24/entrez PY - 2012/4/24/pubmed PY - 2012/8/4/medline SP - e35577 EP - e35577 JF - PloS one JO - PLoS ONE VL - 7 IS - 4 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22523602/The_adult_human_brain_harbors_multipotent_perivascular_mesenchymal_stem_cells_ L2 - http://dx.plos.org/10.1371/journal.pone.0035577 DB - PRIME DP - Unbound Medicine ER -