Human adipose‐derived stem cells (ASCs) have become an increasing interest to both stem cell biologists and clinicians because of their potential to differentiate into adipogenic, osteogenic, chondrogenic, and other mesenchymal lineages, as well as other clinically useful properties attributed to them, such as stimulation of angiogenesis and suppression of inflammation. ASCs have already been used in a number of clinical trials, and some successful outcomes have been reported, especially in tissue reconstruction. However, a critical review of the literature reveals considerable uncertainty about the true clinical potential of human ASC. First, the surgical needs that ASC might answer remain relatively few, given the current difficulties in scaling up ASC‐based tissue engineering to a clinically useful volume. Second, the differentiation of ASC into cell lineages apart from adipocytes has not been conclusively demonstrated in many studies due to the use of rather simplistic approaches to the confirmation of differentiation, such as the use of nonspecific histological dyes, or a small number of molecular markers of uncertain significance. Third, the ASC prepared from human lipoaspirate for different studies differ in purity and molecular phenotype, with many studies using cell preparations that are likely to contain heterogeneous populations of cells, making it uncertain whether ASC themselves are responsible for effects observed. Hence, while one clinical application already looks convincing, the full clinical potential of ASC awaits much deeper investigation of their fundamental biology. STEM CELLS 2011,29:404–411
Mesenchymal stem cell (MSC) and progenitor cell (MPC) populations in human dermis remain poorly characterized, despite their importance to wound repair and the pathogenesis of many skin diseases. To identify MSC/MPC populations in human dermis we developed an 11-marker flow cytometry technique that enabled sorting of mesenchymal cell populations for functional assays, using adipose-derived stem cells (ASCs) from human adipose tissue as a positive control. Two populations of dermal cells had similar phenotypes to ASCs: both were CD34(+) CD73(+) CD105(-)/low, and lacked expression of c-kit (CD117) and hematopoietic or vascular markers (CD31, CD45, CD146, and HLA-DR). However, whereas ASCs were CD36(+/-) CD90(+), dermal mesenchymal progenitor cells (DMPCs) were split between a dominant CD36(-) CD90(+) population (DMPC1) and a small CD36(+) CD90(-) population (DMPC2). Both these populations were capable of differentiating into adipocytes, but only DMPC1 localized to a perivascular location, similar to that reported for ASCs. Re-gating of the flow cytometry data revealed that both DMPC1 and DMPC2 were part of CD45(-) CD73(+) CD146(-) populations with variable expression of CD34. This suggests that CD34 may not be a stable marker of DMPC populations in human dermis, consistent with data from MSCs in human bone marrow, and with the loss of CD34 we observed from both ASCs and DMPCs on cell culture. These data enable future study of DMPCs in health and disease, and may also explain why some mesenchymal cell lines derived from human dermis exhibit characteristics of MSCs.
Human adipose-derived mesenchymal stromal cells (ASC) are showing clinical promise for the treatment of a range of inflammatory and degenerative conditions. These lipoaspirate-derived cells are part of the abundant and accessible source of heterogeneous stromal vascular fraction (SVF). They are typically isolated and expanded from the SVF via adherent cell culture for at least 2 weeks and as such represent a relatively undefined population of cells. We isolated ex vivo ASC directly from lipoaspirate using a cocktail of antibodies combined with immunomagnetic bead sorting. This method allowed for the rapid enrichment of a defined and untouched ex vivo ASC population (referred to as MACS-derived ASC) that were then compared to culturederived ASC. This comparison found that MACS-derived ASC contain a greater proportion of cells with activity in in vitro differentiation assays. There were also significant differences in the secretion levels of some key paracrine molecules. Moreover, when the MACS-derived ASC were subjected to adherent tissue culture, rapid changes in gene expression were observed. This indicates that culturing cells may alter the clinical utility of these cells. Although MACS-derived ASC are more defined compared to culture-derived ASC, further investigations using a comprehensive multicolor flow cytometry panel revealed that this cell population is more heterogeneous than previously appreciated. Additional studies are therefore required to more precisely delineate phenotypically distinct ASC subsets with the most therapeutic potential. This research highlights the disparity between ex vivo MACS-derived and culture-derived ASC and the need for further characterization.
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