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Renal stem cells: characterization of their possible role in kidney pathologies and as new therapeutic tools. RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy . 700.000.000 people in the world have chronic kidney disease.
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Renal stem cells: characterization of their possible role in kidney pathologies and as new therapeutic tools RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, UniversityofFlorence, Italy
700.000.000 people in the world havechronickidneydisease Szczech LA et al. JASN, 2009 Ortelius:TheathrumOrbisTerrarum, 1603 Edition
Salamanderlimbisregeneratedupon differentiationof multiple progenitors Kragl M et al. Nature, 2009 Little MH et al. JASN 2007
2007 Renalprogenitors Sagrinati et al. JASN 2006 “...The capsule isthenseento pass off into the basement membrane of the tube, as the body of a Florenceflaskintohishead…....” Sir William Bowman, 1842
2008 Eliana Parente Elisa Ronconi Maria Lucia Angelotti Lara Ballerini Laura Lasagni Benedetta Mazzinghi Elena Lazzeri Costanza Sagrinati
2008-2012 The renopoietic system Romagnani P et al. Nat. RevNephrol, 2013
Renalprogenitors, podocyteprogenitors and tubularprogenitors are distinguishedfromdifferentiatedcellsbecauseofspecificmarkers and resistancetodeath PodocyteProgenitors Podocytes renalprogenitors podocyteprogenitors RenalProgenitors Tubularcells tubularprogenitors Tubularcells TubularProgenitors Sagrinati C et al. JASN 2006; Mazzinghi B et al. JEM 2008; Ronconi E et al. JASN 2009; AngelottiMLet al. StemCells, 2012
Mammalsgained a considerablyincreasednumberofnephrons in comparisontofish, and thusretainedonly the capacitytoregenerateinjuredportionsof the nephrons Romagnani P et al. Nat. RevNephrol, 2013
Why ESKD occurs? 28y 49y 22y 36y 1628 1655 1634 1642 54y 63y Rembrandt, Portraits of the Artist (1606-1669) 1.Number ofnephronslargelyexceedsourneeds at birth and declinesonlywithaging, beyondevolutionaryrequirements 1669 1660
2009 REGENERATION ? glomerulosclerosis Smeets B, AngelottiMLet al, JASN, 2009 2.Renal progenitorsdysfunction can leadto ESKD Smeets B, AngelottiMLet al. JASN 2009; Smeets B et al. JASN 2011
Impaired Regeneration Deregulated Regeneration Regeneration Glomerularepithelialstemcells: the good, the bad and the ugly. JASN. 2010
Proteinuria impairsglomerularregeneration and inducesglomerulosclerosis 2013 Treatment withretinoic acid promotesregeneration and regressionofglomerulosclerosis Peired A etal. J Am SocNephrol 2013
The novelstrategytoprevent and treatrenalfailureisto modulate the regenerativecapacityof the kidney Michelangelo. Separation of Earth and Waters. Sistine Ceiling 1511.
2010 MeyerChildren’s Hospital
2010 Nephrology and DialysisUnit
Marco Materassi Rosa Roperto Elena Lazzeri Duccio Lombardi Maria Lucia Angelotti Anna Peired Elisa Ronconi Benedetta Mazzinghi Francesca Becherucci Laura Lasagni Alessandro Sisti