renal stem cells: characterization of their possible role in kidney pathologies and as new...
TRANSCRIPT
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
Szczech LA et al. JASN, 2009 Ortelius:Theathrum Orbis Terrarum, 1603 Edition
700.000.000 people in the world have chronic kidney disease
Michelangelo. Pietà per Vittoria Colonna. 1546
Salamander limb is regenerated upon differentiation of multiple progenitors
Kragl M et al. Nature, 2009Little MH et al. JASN 2007
The nephron: an evolutionary link
“...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
2008
Lara Ballerini
BenedettaMazzinghi
ElianaParente
LauraLasagni Elena
Lazzeri
Maria LuciaAngelotti
CostanzaSagrinati
ElisaRonconi
2009
Romagnani P et al. Nat. Rev Nephrol, 2013
The renopoietic system2008-2012
Ren
al P
roge
nito
rs
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
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
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?
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
Regeneration
ImpairedRegeneration
DeregulatedRegeneration
Glomerular epithelial stem cells: the good, the bad and the ugly. JASN. 2010
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
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
2010 Nephrology and Dialysis Unit
Francesca Becherucci
AnnaPeired
Elisa Ronconi
Maria LuciaAngelotti
AlessandroSisti
DuccioLombardi
ElenaLazzeri
MarcoMaterassi
LauraLasagni
Benedetta Mazzinghi
Rosa Roperto
