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
http://erc.europa.eu/index.cfm
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
http://upload.wikimedia.org/wikipedia/commons/5/58/Piet%C3%A0_per_Vittoria_Colonna.jpg
Salamander limb is regenerated upon
differentiation of multiple progenitors
Kragl M et al. Nature, 2009 Little 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 Benedetta
Mazzinghi
Eliana
Parente Laura
Lasagni Elena
Lazzeri
Maria Lucia
Angelotti
Costanza
Sagrinati
Elisa
Ronconi
2009
Romagnani P et al. Nat. Rev Nephrol, 2013
The renopoietic system 2008-2012
Ren
al P
rog
enit
ors
Podocytes
Tubular cells
Tub
ula
r P
rog
enit
ors
Tubular cells
renal progenitors
tubular progenitors
Po
do
cyte
Pro
gen
ito
rs
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)
1669 1660
1642 1628 1634 1655
22y 28y 36y 49y
54y 63y
Why ESKD occurs?
//upload.wikimedia.org/wikipedia/commons/f/fe/Rembrandt_van_Rijn_184.jpg//upload.wikimedia.org/wikipedia/commons/7/72/Rembrandt_-_Self-Portrait_with_Velvet_Beret_-_Google_Art_Project.jpghttp://www.google.it/url?sa=i&rct=j&q=number+of+nephrons+and+aging&source=images&cd=&cad=rja&docid=4_OQWZ45ZCqIuM&tbnid=V-_Kn82QXDwN3M:&ved=0CAUQjRw&url=http://www.readcube.com/articles/10.1038/ki.2010.128&ei=aCMUUaniOY74sgak6YCACQ&psig=AFQjCNFjCBFTLoRYMWnL6DVwLGOGkJZWnw&ust=1360359553876615
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
Impaired
Regeneration Deregulated
Regeneration
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 Meyer Children’s Hospital
http://www.google.it/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=4_0fPIotuB_P8M&tbnid=3nJ-Io_GZhNIhM:&ved=0CAUQjRw&url=http://www.meyer.it/notizia.php?IDNotizia=6460&IDCategoria=383&ei=J8VrUvy_C4HQtAbw0YGYBQ&psig=AFQjCNHFtRArGDM6SiQI4ctFuqHrmWWuQQ&ust=1382879867126606
2010 Nephrology and Dialysis Unit
http://www.isnforefronts.org/2013/florence/
Francesca Becherucci
Anna Peired
Elisa Ronconi
Maria Lucia Angelotti
Alessandro Sisti
Duccio Lombardi
Elena Lazzeri
Marco Materassi
Laura Lasagni
Benedetta Mazzinghi
Rosa Roperto
No child health without research!
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