RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy
description
Transcript of RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy
![Page 1: RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/1.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/2.jpg)
Szczech LA et al. JASN, 2009 Ortelius:Theathrum Orbis Terrarum, 1603 Edition
700.000.000 people in the world have chronic kidney disease
![Page 3: RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/3.jpg)
Michelangelo. Pietà per Vittoria Colonna. 1546
![Page 4: RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/4.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/5.jpg)
The nephron: an evolutionary link
![Page 6: RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/6.jpg)
“...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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/7.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/8.jpg)
2009
![Page 9: RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/9.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/10.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/11.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/12.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/13.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/14.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/15.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/16.jpg)
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](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/18.jpg)
2010 Nephrology and Dialysis Unit
![Page 20: RESCARF Starting Grant 2008-2012: 820200 euros Paola Romagnani, University of Florence , Italy](https://reader036.fdocuments.in/reader036/viewer/2022062813/56816678550346895dda168f/html5/thumbnails/20.jpg)
Francesca Becherucci
AnnaPeired
Elisa Ronconi
Maria LuciaAngelotti
AlessandroSisti
DuccioLombardi
ElenaLazzeri
MarcoMaterassi
LauraLasagni
Benedetta Mazzinghi
Rosa Roperto