A Perivascular Origin for Mesenchymal Stem Cells in Multiple Human Organs

Abstract

Mesenchymal stem cells (MSCs), the archetypal multipotent progenitor cells derived in cultures of developed organs, are of unknown identity and native distribution. We have prospectively identified perivascular cells, principally pericytes, in multiple human organs including skeletal muscle, pancreas, adipose tissue, and placenta, on CD146, NG2, and PDGF-Rb expression and absence of hematopoietic, endothelial, and myogenic cell markers. Perivascular cells purified from skeletal muscle or nonmuscle tissues were myogenic in culture and in vivo. Irrespective of their tissue origin, long-term cultured perivascular cells retained myogenicity; exhibited at the clonal level osteogenic, chondrogenic, and adipogenic potentials; expressed MSC markers; and migrated in a culture model of chemotaxis. Expression of MSC markers was also detected at the surface of native, noncultured perivascular cells. Thus, blood vessel walls harbor a reserve of progenitor cells that may be integral to the origin of the elusive MSCs and other related adult stem cells.

Concise Review: Wharton's Jelly: The Rich, but Enigmatic, Source of Mesenchymal Stromal Cells

“…An influential study by Crisan et al showed that MSCs could be obtained by isolating populations of perivascular cells from a wide range of adult and fetal tissues 52, creating a strong link between MSCs and a specific location in situ. The term “perivascular cells” commonly includes classically defined pericytes surrounding the microvasculature, as well as other nonpericyte cells within the perivascular niche of the macrovasculature which have also been shown to display properties of MSCs 53, 54, 55.…”

Phenotypes of stem cells from diverse origin

“…Therefore, we asked all authors to revisit the table and upgrade their part either by own data or based on additional literature, as necessary. This resulted in the upgraded Table 1 showing phenotypes of very small embryonic-like stem cells (vSELs) (5,6), neural stem cells (NSCs) (7)(8)(9)(10)(11)(12)(13)(14)(15)(16), hematopoietic stem cells (HSCs) from two organs (4,17), MSCs (4,18), EpSC (4), limbal epithelial stem cells (LSCs) (19), endothelial progenitor cells (EPCs) from different organs (3,4,(20)(21)(22)(23)(24)(25), supra-adventitial adipose stromal cells (SA-ASCs) (3,(22)(23)(24)(25), adipose pericytes (pericyte) (3,(22)(23)(24)(25), and finally cancer stem cells (CSCs) (26).…”

“…VI (4) VII (19) VIII (20,21) IX (3,(22)(23)(24)(25) X (4) XI (3,(22)(23)(24)(25) XII (3,(22)(23)(24)(25) XIII ( (17) IV (4) V (4,18) VI (4) VII (19) VIII (20,21) IX (3,(22)(23)(24)(25) X (4) XI (3,(22)(23)(24)(25) XII (3,(22)(23)(24)(25) XIII (26) RHAMM/HMMR marker expression in the same stem cell lineage obtained from various tissues may indicate differences in their pluripotency. It is also possible that stem cell marker expression pattern and levels depend on respective cell cycle phases.…”

Cellules souches mésenchymateuses

“…En Europe, les CSM sont considérées comme des médi-caments de thérapie innovante (MTI ou advanced therapy medicinal products , ATMP) comme le définit la directive (CE) n o 1394/2007 du Parlement européen et [1,2], le passage des protocoles de recherche à des protocoles de production à grande échelle respectant les BPF nécessite une analyse approfondie de tous les aspects critiques [3]. Comme pour toute production de cellules à usage clinique, la production des CSM doit se faire dans un environnement spécifique, sous une hotte à flux laminaire (classe A) placée dans une pièce qui est en surpression et dont on maintient le taux d'empoussièrement très bas (classe B).…”