Adipose tissue: challenging the marrow monopoly.

At a recent international meeting on the subject of cellular therapy one speaker prefaced his presentation by commenting that if he were to injure his arm, mesenchymal stem cells (MSC) would mobilize from his BM, travel to the site of the injury, and participate in the repair and healing process. As a working model this is perfectly reasonable. MSC are clearly present in BM, albeit at low frequency, and the other BM stem cell populations (hematopoietic stem cells, HSC [1] and endothelial precursor cells, EPC [2]) are excellent precedents for mobilization. Donald Orlic’s work in an experimental myocardial infarct model represents a potential link between these observations showing the ability of the combination of stem cell factor and G-CSF, a combination known to induce HSC mobilization, to improve myocardial function and survival in rats [3]. However, the fact that HSC and EPC can be mobilized from BM does not mean that all mobilized MSC are marrow-derived. In this article (following the editor’s request to be controversial and provoke discussion) the author would like to suggest that, in the unfortunate event of the abovementioned speaker injuring his arm, his MSC might not need to travel all the way from his BM but might rather come from an alternate, more conveniently located stem cell reservoir. This possibility arises from recent observations that have demonstrated the presence of MSC-like cells in tissues other than BM, most notably adipose tissue [4,5] and skin [6]. Thus, in early 2001 Marc Hedrick’s laboratory at UCLA described a population of cells derived from adipose tissue that had the ability to differentiate into multiple mesenchymal lineages. Follow-up studies from this laboratory, currently in press, have demonstrated the presence of single cells within the adipose tissue-derived population that have multi-lineage differentiation potential. Adipose tissue therefore contains a population of cells with a phenotype that is very similar to that of marrow-derived MSC. It can be and, of course, has been argued that such cells are in fact derived from the peripheral blood that so frequently contaminates adipose tissue collected by liposuction. However, there is no reason to believe that liposuction generates signals capable of inducing stem cell mobilization, nor have there been reports of HPC in the adipose tissue-derived population. Further, studies in this author’s laboratory have shown that when aspirated adipose tissue is washed to remove contaminating blood, the wash material contains negligible numbers of MSClike cells. These observations suggest that detection of MSC-like cells in adipose tissue is not the result of perioperative contamination with marrow/blood-derived cells, but rather that they are legitimate residents of adipose. This does not necessarily mean that these cells originally derive from adipose; it may be that adipose tissue is colonized by marrow-derived cells during development. Of course, a ‘devil’s advocate’ might respond with the reverse argument, and propose that BM-derived MSC are of adipose origin, after all the BM compartment does contain substantial amounts of adipose tissue. It is perhaps more likely that these cells are both members of the same family, if not brethren then perhaps close cousins, with the further intriguing possibility that both are members of the larger family of vascular pericytes.