Mesenchymal stem cells: from experiment to clinic

There has been an explosion of literature in the field of mesenchymal stem cells (MSCs) in the past 10 years. Many researchers have sought to exploit their potential as a source of reparative cells for clinical use in a variety of contexts. There are, however, several pitfalls that it would be useful to avoid, as MSCs have some awkward properties that may make their use for tissue repair or tissue engineering somewhat risky. In this review, we highlight some recent advances in the understanding of the cell biology of MSCs, and how these may integrate into strategies for more clinical applications.Adult MSCs are generally thought of as an autologous source of reparative cells, in contrast to the totipotent, and allogeneic embryonic stem cells (ESCs). A major source of adult stem cells is the bone marrow (BM), from which two main populations derive: haematopoietic stem cells (HSCs), which produce the blood-cell lineages, and MSCs, which provide the bone-marrow stromal niche and have the potential to produce several cell lineages, including adipogenic, osteogenic and chondrogenic lineages. BM also contains endothelial precursor cells (EPCs) and probably a common precursor of all three stem-cell types, which remains somewhat less well defined. Recent reports suggest that MSCs may differentiate into endothelial cells [1,2], an outcome that may depend on the cytokine context. MSCs can also be obtained from the stromal fraction of lipoaspirates of adipose tissue [3], and these possess similar properties to BM-derived MSCs. Further sources of human MSCs include the intestinal [4], limbal [5], knee-joint [6-9] and prostate [10] stroma, trachea [11], nasal mucosa [12], Wharton's jelly (WJ) [13,14], cord blood [15] and placenta [16]. MSCs-like cells have also been extracted from tumour stroma [17], and may have an important role in the fibrotic responses, as reported for the rat kidney [18] and rat heart [19]. Thus, these cells are becoming almost ubiquitous residents in many