Alessandro Giacomello, Dipartimento di Medicina
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Alessandro Giacomello, Dipartimento di Medicina
Alessandro Giacomello, Dipartimento di Medicina Sperimentale e Patologia, Policlinico Umberto I, Universita’ degli Studi di Roma “La Sapienza”, Viale Regina Elena 324, 00161 ROMA. Tel: 06 4461481; Fax: 06/4454820; email: [email protected]. Qualifica: Professore Ordinario di Patologia Generale, Facolta’ di Farmacia, Corso di Laurea in Biotecnologie. Area di Ricerca: Genetica molecolare degli eucarioti Titolo (Title): Biology and physiology of adult cardiac stem/progenitor cells with a view to optimizing their utility for autologous cell transplantation. Aims: This project characterizes the cell biology and physiology of cardiac stem cells (CSCs) and cardiospheres (CSps) with a view to optimizing their utility for cell transplantation. The aims are grouped into three categories, as follows: 1. Improved methods to optimize the culture conditions for CSCs 1A.To develop culture media that support CSC expansion without xenogeneic serum. 1B. To develop culture conditions that favor CSC differentiation into cardiac myocytes in vitro. 2. Cell biology of CSCs and CSps 2A.To determine the origin of human CSCs in transplanted hearts (host versus donor) 2B. To test the idea that CSCs can arise from de-differentiated adult cardiac myocytes 2C. To characterize the physiological properties of CSCs at various stages of differentiation 2D. To compare the phenotypes of CSCs and CSps derived from atrial muscle and ventricular muscle during the prenatal cardiogenesis development (MLC3F-nLacZ and/or cTnI-nLacZ transgenic mouse) and adult human (endomiocardial bioptical sample and appendage specimens) and transgenic mouse: are regional features retained, or are all CSCs created equal? 2E. To examine the effects of heart failure, coronary artery disease and aging on CSC yield, growth, migration and differentiation in vitro 3. Integrative function to assess functional integration between transplanted human CSCs and primary rat cardiac myocytes in an in vitro co-culture system and in vivo after injection into the SCID mouse. 1 15. Matsuura K, Nagai T, Nishigaki N, Oyama T, Nishi J, Wada H, Sano M, Toko H, Akazawa H, Sato T, Nakaya H, Kasanuki H, Komuro I. Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes. J Biol Chem. 2004 Mar 19;279(12):11384-91. Epub 2003 Dec 31. 16. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A. Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ Res. 2004 Oct 29;95(9):911-21. Epub 2004 Oct 7. 17. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR. Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature. 2005 Feb 10;433(7026):647-53. 18. Rachel Ruckdeschel Smith, M. Roselle Abraham, Elisa Messina, Hee Cheol Cho, Alessandro Giacomello, Eduardo Marbán. Electrophysiology of human and porcine adult cardiac stem cells isolated from endomyocardial biopsies. American Heart Association Abstract 2004. Researchers who participate in this project are: A) From the University of Rome “La Sapienza”, Dipartimento di Medicina Sperimentale e Patologia Alessandro Giacomello (professore ordinario), Elisa Messina (professore a contratto), Giacomo Frati (professore associato), Deleana Pozzi (ricercatore), Lucio Barile (dottorando), Isotta Chimenti, Roberto Gaetani, Elvira Forte (studenti del Corso di Laurea in Biotecnologie Mediche). B) From the Johns Hopkins University, Department of Cardiology (con cui La Sapienza ha un accordo di collaborazione culturale e scientifica sul tema: “Caratterizzazione ed impiego di cellule staminali adulte cardiache nella terapia delle cardiomiopatie”) Eduardo Marban (Director of the Department), M. Roselle Abraham, M.D., and Hee Cheol Cho, Ph.D. Rachel Ruckdeschel Smith (student). C) From the University of Milan “Milano Bicocca”, Dipartimento di Biotecnologie e Bioscienze Sergio Ottolenghi (professore ordinario). Papers published by Alessandro Giacomello during the last two years: 1: Messina E, Micheli V, Giacomello A. Guanine nucleotide depletion induces differentiation and aberrant neurite outgrowth in human dopaminergic neuroblastoma lines: a model for basal ganglia dysfunction in Lesch-Nyhan disease. Neurosci Lett. 2005 Feb 28;375(2):97-100. Epub 2004 Dec 10. 2: Messina E, Lupi F, Barile L, Giacomello A. Cyclic nucleotides and neuroblastoma differentiation.Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1551-4. 3: Messina E, Barile L, Lupi F, Giacomello A. Potential role of mycophenolate mofetil in the management of neuroblastoma patients. Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1545-9. 4: Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, Battaglia M, Latronico MV, Coletta M, Vivarelli E, Frati L, Cossu G, Giacomello A. Isolation and expansion of adult cardiac stem cells from human and murine heart.Circ Res. 2004 Oct 29;95(9):911-21. Epub 2004 Oct 7. 9