Clear up this stem-cell mess

Confusion about mesenchymal stem cells is making it easier for people to sell unproven treatments, warn Douglas Sipp, Pamela G. Robey and Leigh Turner.

Leigh Turner

Scanning electron micrograph of what is called a human mesenchymal stem cell, which some say can develop into bone, cartilage or fat cells.Credit: Steve Gschmeissner/SPL

Various populations of cells in the adult human body have been the subject of controversy since the early 2000s. Contradictory findings about these haphazardly termed ‘mesenchymal stem cells’, including their origins, developmental potential, biological functions and possible therapeutic uses, have prompted biologists, clinicians and scientific societies to recommend that the term be revised or abandoned. Last year, even the author of the paper that first used the term mesenchymal stem cells (MSCs) called for a name change1.

Tissue-specific stem cells, which have a limited ability to turn into other cell types, are the norm in most of the adult body. Several studies indicate that the variety of cells currently dropped into the MSC bucket will turn out to be various tissue-specific cell types, including stem cells2.

Yet the name persists despite the evidence pointing to this, and almost two decades after questions about the validity of MSCs were first raised. A literature search indicates that, over the past 5 years, more than 3,000 research articles referring to MSCs have been published every year (see ‘Tenacious term’). And several national regulatory agencies have now licensed MSC-based drugs, although most of these approvals have been provisional or are based on underpowered studies (see ‘Doubtful drugs’).

In our view, the wildly varying reports have helped MSCs to acquire a near-magical, all-things-to-all-people quality in the media and in the public mind3 — hype that has been easy to exploit. MSCs have become the go-to cell type for many unproven stem-cell interventions. The confusion must be cleared up.

What is needed is a coordinated global effort to improve understanding of the biology of the cells currently termed MSCs, and a commitment from researchers, journal editors and others to use more-precise labels. We must develop standardized analyses of gene expression, including on a cell-by-cell basis, and rigorous assays to establish the precise products of cell differentiation in various tissues. Such efforts could put an end to lingering questions about MSC identity and function, once and for all.