rescarf starting grant 2008-2012: 820200 euros paola romagnani, university of florence , italy

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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

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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. - PowerPoint PPT Presentation

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Page 1: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Renal stem cells: characterization of their possible role in kidney pathologies and as

new therapeutic tools

RESCARFStarting Grant 2008-2012: 820200 euros

Paola Romagnani, University of Florence, Italy

Page 2: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Szczech LA et al. JASN, 2009 Ortelius:Theathrum Orbis Terrarum, 1603 Edition

700.000.000 people in the world have chronic kidney disease

Page 4: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Salamander limb is regenerated upon differentiation of multiple progenitors

Kragl M et al. Nature, 2009Little MH et al. JASN 2007

Page 5: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

The nephron: an evolutionary link

Page 6: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

“...The capsule is then seen to pass off into the basement membrane of the tube, as the body of a Florence flask into his head…....” Sir William Bowman, 1842

Renal progenitors

2007

Sagrinati et al. JASN 2006

Page 7: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

2008

Lara Ballerini Benedetta

Mazzinghi

ElianaParente

LauraLasagni Elena

Lazzeri

Maria LuciaAngelotti

CostanzaSagrinati

ElisaRonconi

Page 8: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

2009

Page 9: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Romagnani P et al. Nat. Rev Nephrol, 2013

The renopoietic system2008-2012

Page 10: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Rena

l Pr

ogen

itors

Podocytes

Tubular cells

Tubu

lar P

roge

nito

rs Tubular cells

renal progenitors

tubular progenitors

Podo

cyte

Pro

geni

tors

Sagrinati C et al. JASN 2006; Mazzinghi B et al. JEM 2008;Ronconi E et al. JASN 2009; Angelotti ML et al. Stem Cells, 2012

podocyte progenitors

Renal progenitors, podocyte progenitors and tubular progenitors are distinguished

from differentiated cells because of specific markers and resistance to death

Page 11: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Romagnani P et al. Nat. Rev Nephrol, 2013

Mammals gained a considerably increased number of nephrons in comparison to fish, and thus retained only the capacity to

regenerate injured portions of the nephrons

Page 12: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

1.Number of nephrons largely exceeds our needs at birth and declines only with aging, beyond evolutionary requirements

Rembrandt, Portraits of the Artist (1606-1669)16691660

16421628 1634 1655

22y 28y 36y 49y

54y 63y

Why ESKD occurs?

Page 13: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Smeets B, Angelotti ML et al, JASN, 2009

Smeets B, Angelotti ML et al. JASN 2009; Smeets B et al. JASN 2011

2.Renal progenitors dysfunction can lead to ESKD

REGENERATION

glomerulosclerosis

?

2009

Page 14: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Regeneration

ImpairedRegeneration

DeregulatedRegeneration

Glomerular epithelial stem cells: the good, the bad and the ugly. JASN. 2010

Page 15: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Proteinuria impairs glomerular regeneration and induces glomerulosclerosis

Treatment with retinoic acid promotes regeneration and regression of glomerulosclerosis

2013

Peired A etal. J Am Soc Nephrol 2013

Page 16: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Michelangelo. Separation of Earth and Waters. Sistine Ceiling 1511.

The novel strategy to prevent and treat renal failure is to modulate the regenerative capacity of the kidney

Page 18: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

2010 Nephrology and Dialysis Unit

Page 20: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

Francesca Becherucci

AnnaPeired

Elisa Ronconi

Maria LuciaAngelotti

AlessandroSisti

DuccioLombardi

ElenaLazzeri

MarcoMaterassi

LauraLasagni

Benedetta Mazzinghi

Rosa Roperto

Page 21: RESCARF Starting Grant 2008-2012: 820200  euros Paola Romagnani,  University of Florence , Italy

No child health without research!