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!

http://erc.europa.eu/index.cfm