Increasing evidence suggests that multipotent mesenchymal stem cells/bone marrow stromal cells (MSC) represent an ontologic and phylogenetic vestige of ancestors with regenerative potential, as found during early development of mammals or adult newts, salamanders and fishes. MSC can be isolated from virtually all vascularized tissues and are proposed to correspond with the pericyte compartment. Since MSC can be robustly expanded ex vivo and present low immunogenicity, allowing both autologous and allogeneic transplants, many novel cellular therapies explore the potential of MSC: these cells can robustly differentiate into tissues such as bone, cartilage and tendon, allowing their use as replacement for damaged tissue. But many other clinical applications rely on their production and release of paracrine signals with chemotactic, immune suppressive and pro-angiogenic activity; for many therapies currently undergoing phase III clinical trials, such as graft versus host disease, cardiac infarction and epidermal fistulas, administered MSC are considered not to contribute significantly by direct differentiation and replacement of the damaged tissue, but rather to perform as trophic mediators, promoting tissue repair by release of soluble factors that inhibit inflammation, reduce fibrosis, and induce angiogenesis among other functions. Based on recombinant DNA techniques, we primary work altering gene and microRNA expression levels of human MSC to either optimize their therapeutic potential for applications such as bone repair, non-healing ulcers and critical limb ischemias or to understand the basic mechanisms involved in differentiation, proliferation, self-renewal, etc.
2014 Clark L, Kalmomoiris S, Nolta JA, Fierro F. Concise review: MicroRNA function in multipotent mesenchymal stromal cells. Stem Cells. (available online).
2013 Poitz DM, Stölzel F, Arabanian, Friedrichs J, Docheva D, Schieker M, Fierro FA, Platzbecker U, Ordemann R, Werner C, Bornhäuser M, Strasser R, Ehninger G, Illmer T. MiR-134-Mediated β1 Integrin Expression and Function in Mesenchymal Stem Cells. Biochemical and Biophyssical Acta, 1833(12):3396-3404.
2011 Fierro FA, Kalomoiris S, Sondergaard CS, Nolta JA. Effects on proliferation and differentiation of multipotent bone marrow stromal cells engineered to express growth factors for combined cell and gene therapy. Stem Cells, 29(11):1727-37.
2011 Ovcharenko D, Stölzel F, Poitz D, Fierro FA, Schaich M, Neubauer A, Kelnara K, Davison T, Müller-Tidow C, Thiede C, Bornhäuser M, Ehninger G, Brown D, Illmer T. miR-10a overexpression is associated with NPM1 mutations and MDM4 downregulation in intermediate-risk acute myeloid leukemia. Exp Hematol, 39(10):1030-1042.
2011 Gruenloh W, Kambal A, Sondergaard C, McGee J, Olson SD, Fierro F, Nolta JA. Characterization and in vivo testing of mesenchymal stem cells derived from human embryonic stem cells. Tissue Engineering Part A, 17(11-12):1517-25.
2009 Egaña JT, Fierro FA, Krüger S, Bornhäuser M, Huss R, Lavandero S, Machens HG. Use of human mesenchymal cells to improve vascularization in a mouse model for scaffold-based dermal regeneration. Tissue Engineering Part A. 2009 May. 15(5):1191-200.
2007 Fierro F, Illmer T, Jing D, Schleyer E, Ehninger G, Boxberger S, Bornhäuser M. Inhibition of platelet-derived growth factor receptorbeta by imatinib mesylate suppresses proliferation and alters differentiation of human mesenchymal stem cells in vitro. Cell Proliferation, 40(3):355-66.
2005 Minguell JJ, Fierro FA, Epuñan MJ, Erices AA, Sierralta WD. Nonstimulated human uncommitted mesenchymal stem cells express cell markers of mesenchymal and neural lineages. Stem Cells and Develpment, 14(4):408-14.