Scientists have identified a new characteristic that could be used to identify progenitor cells that are particularly likely to differentiate into bone, cartilage and fat, respectively. Instead of the usual cell surface markers, they measured the mechanical characteristics of one type of stem cell, the mesenchymal stem cell, and were able to predict whether a given cell was more likely to differentiate into bone, cartilage or fat.
Cartilage, bone and fat come from different progenitor cells – chondrocytes, osteoblasts and adipocytes, respectively. Those progenitor cells, in turn, come from a common stem cell, the mesenchymal stem cell.
As stem cells go, mesenchymal cells are fairly easy to get one's hands on. Cytori Inc. is developing fat stem cells for both reconstructive surgery and heart disease, and there is a body of research on how to get those cells to turn into bone. Eric Darling's rather dry description is that "they are easy to get and quite abundant, and people aren't sorry to see them go," since they are gathered via liposuction. Darling is an assistant professor of medical science at Brown University and the senior author of the new study, which appeared in the May 21, 2012, advance online edition of the Proceedings of the National Academy of Sciences.
Stem cells are currently defined, and isolated from tissue, by surface markers. But there is no universally accepted set of markers, meaning that there is always some uncertainty about whether a cell truly is a stem cell.
And, Darling told BioWorld Today, such sorting also can be too specific.
Clinical applications need millions of cells. Such cells can, of course, be grown from small amounts of stem cells in the lab, at least in theory. But most stem cells are not inexhaustible; the more growth and culturing is necessary in the laboratory, the more time-consuming, expensive and prone to contamination the overall procedure becomes.
Darling said he first noticed that stem cells have different biomechanical properties while doing research on stem and progenitor cells that would ultimately turn into cartilage. For cartilage cells, "mechanical properties are very important," since the cells need to withstand constant mechanical wear and tear.
It's easy to realize that a bone cell and a fat cell are very different in their biomechanical requirements. But during those experiments, Darling also found that the stem cells that produce those cells already were noticeably different in their mechanical properties – "osteoblasts were stiffer than adipocytes," perhaps because the cells start down a differentiation path before their surface markers give any indication of their doing so.
In their current set of experiments, Darling and co-authors Rafael Gonzalez-Cruz and Vera Fonseca tested the mechanical properties of mesenchymal stem cells – specifically, how viscous and how elastic they were. They then induced the cells to differentiate, measured their metabolic profiles and then correlated the mechanical profiles with what type of cell the stem cells were most likely to become. Most cells still were capable of differentiating into two of the three cell types, and almost half of them were able to become all three. Using mathematical modeling, they predicted that by measuring mechanical properties, they would be able to significantly enrich cell populations for each of the three progenitor cell types.
Darling and his team plan to investigate in greater detail why biomechanical properties of stem cells predict their propensity to turn into certain cell types.
They also want to find a way to speed up the sorting process. For all the shortcomings of surface biomarkers, fluorescence-activated cell sorting, the technique that is used to sort cells via those surface markers, is high-throughput. In contrast, atomic force microscopy, which Darling and his team used in their experiments, is rather artisanal. In order for biomechanical properties to become a feasible biomarker for practical applications, he said, it will be necessary to develop a high-throughput method – something akin to a filter or, more likely, a microfluidic device – to measure those properties.