title: The gap between the physiological and therapeutic roles of mesenchymal stem cells.
abstract: Several investigators have cultivated marrow stromal cells and have identified a population of mesenchymal stem cells (MSCs). These cells expand extensively in vitro and exhibit multilineage differentiation potential. The lack of MSC-specific markers impedes identification of MSC functions. Further in vivo studies of these cells may elucidate the nature of MSCs. Although the nature of MSCs remains unclear, nonclonal stromal cultures are used as a source of putative MSCs for therapeutic purposes. Preclinical studies and clinical trials assumed that transplanted MSCs exert their effects through their differentiation properties or through the release of molecules that restore tissue functions and modulate immune cells. These studies reported contradictory results and failed to meet expectations. Thus, it is important to note that current protocols for MSC therapy are primarily based on the use of in vitro expanded nonclonal MSCs. Clearly defining the physiological features of in situ MSCs and the in vitro and in vivo properties of nonclonal cultures of stromal cells, which are often misidentified as pure stem cell cultures, may explain the reported failures of MSC therapy. This review will address these issues.
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania; Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy; Genkök Stem Cell Centre, Erciyes University, Kayseri, Turkey.
authors.forename: Umberto
authors.initials: U
authors.lastname: Galderisi
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D015415:Biomarkers; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation
chemical_list: D015415:Biomarkers
keywords: differentiation; engraftment; immunomodulation; paracrine effects; secretome; transplants