Fierro, Fernando A. - University of California, Davis - Department of Cell Biology and Human Anatomy

研究领域

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.

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Kalomoiris S, Cicchetto AC, Lakatos K, Nolta JA, Fierro FA. Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow-Derived Mesenchymal Stem Cells. J Cell Biochem. 2016 Sep;117(9):2128-37. Beegle JR, Magner NL, Kalomoiris S, Harding A, Zhou P, Nacey C, White JL, Pepper K, Gruenloh W, Annett G, Nolta JA, Fierro FA. Preclinical evaluation of mesenchymal stem cells overexpressing VEGF to treat critical limb ischemia. Mol Ther Methods Clin Dev. 2016 Aug 24;3:16053. Chávez MN, Aedo G, Fierro FA, Allende ML, Egaña JT. Zebrafish as an Emerging Model Organism to Study Angiogenesis in Development and Regeneration. Front Physiol. 2016 Mar 8;7:56. Man AJ, Kujawski G, Burns TS, Miller EN, Fierro FA, Leach JK, Bannerman P. Neurogenic potential of engineered mesenchymal stem cells overexpressing VEGF. Cell Mol Bioeng. 2016 Mar 1;9(1):96-106. Lakatos K, Kalomoiris S, Merkely B, Nolta JA, Fierro FA. Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols. J Cell Biochem. 2016 Feb;117(2):300-7. Fierro FA, O'Neal AJ, Beegle JR, Chávez MN, Peavy TR, Isseroff RR, Egaña JT. Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells. Front Cell Dev Biol. 2015 Oct 30;3:68. Wahl EA, Fierro FA, Peavy TR, Hopfner U, Dye JF, Machens HG, Egaña JT, Schenck TL. In Vitro Evaluation of Scaffolds for the Delivery of Mesenchymal Stem Cells to Wounds. Biomed Res Int. 2015;108571. Beegle J, Lakatos K, Kalomoiris S, Stewart H, Isseroff RR, Nolta JA, Fierro FA. Hypoxic preconditioning of mesenchymal stromal cells induces metabolic changes, enhances survival, and promotes cell retention in vivo. Stem Cells. 2015 Jun;33(6):1818-28. Arabanian L, Fierro FA, Stölzel F, Heder C, Poitz D, Strasser R, Wobus M, Bornhäuser M, Ferrer R, Platzbecker U, Schieker M, Docheva D, Ehninger G, Illmer T. miRNA-23a mediates post-transcriptional regulation of CXCL12 in bone marrow stromal cells. Hematologica 2014 Jun;99(6):997-1005. Clark L, Kalmomoiris S, Nolta JA, Fierro FA. Concise review: MicroRNA function in multipotent mesenchymal stromal cells. Stem Cells. 2014 May; 32(5):1074-82. 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. Biochim Biophys Acta 2013 Nov. 1833(12):3396-3404. Kumari R, Li H, Haudenschild DR, Fierro F, Carlson CS, Overn P, Gupta L, Gupta K, Nolta J, Yik JH, Di Cesare P. The oncogene LRF is a survival factor in chondrosarcoma and contributes to tumor malignancy and drug resistance. Carcinogenesis. 2012 Nov. 33(11): 2076-83. 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. 2011 Nov. 29(11):1727-37. 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, 2011 Oct. 39(10):1030-1042. 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 Eng Part A. 2011 Jun. 17(11-12):1517-25 Jing D, Fonseca AV, Alakel N, Fierro FA, Muller K, Bornhauser M, Ehninger G, Corbeil D, Ordemann R. Hematopoietic stem cells in coculture with mesenchymal stromal cells - modelling the niche compartments in vitro. Haematologica. 2010 April. 95(4):542-50. Ugarte F, Ryser M, Thieme S, Fierro FA, Navratiel K, Bornhäuser M, Brenner S. Notch signaling enhances osteogenic differentiation while inhibiting adipogenesis in primary human bone marrow stromal cells. Experimental Hematology. 2009 July. 37(7):867-875. 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. Fierro FA, Brenner S, Oelschlaegel U, Jacobi A, Knoth H, Ehninger G, Illmer T, Bornhäuser M. Combining SDF-1/CXCR4 antagonism and chemotherapy in relapsed acute myeloid leukemia. Leukemia. 2009 Feb;23(2):393-6. Fierro FA, Taubenberger A, Puech PH, Ehninger G, Bornhauser M, Muller DJ, Illmer T. BCR/ABL expression of myeloid progenitors increases beta1-integrin mediated adhesion to stromal cells. Journal of Molecular Biology. 2008 Apr 4;377(4):1082-93. 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. 2007 Jun;40(3):355-66. 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 Development. 2005 Aug;14(4):408-14. Fierro FA, Sierralta WD, Epuñan MJ, Minguell JJ. Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination. Clinical and Experimental Metastasis. 2004;21(4):313-9.