 Mesenchymal stem cells, MSCs, are adult stem cells that have shown promising features for regenerative medicine due to their ability to differentiate into diverse cell lineages and exhibit regenerative properties. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy, ISCT, to issue criteria for identifying unique populations of these cells. Non-clonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the U.S. National Institutes of Health. This article provides a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. The article analyzes clinical trials using MSCs for representative diseases, including hematological disease, graft versus host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney, and lung, as well as cardiovascular, bone and cartilage, neurological, and autoimmune diseases. This article was authored by Tiziana Swallaro, John Franco Paluzzo, and Umberto Galdorizzi. We are article.tv, links in the description below.