Gianluca Vadalà, La bellezza delle cellule staminali (Msc and art)

Università Campus Bio-Medico di Roma
Via Álvaro del Portillo, 21 - 00128 Roma - Italia
1Department of Orthopaedic and Trauma Surgery, Campus University Bio-Medico of Rome, Italy
2Cell Factory, Center of Transfusion Medicine, Cellular Therapy and Cryobiology, Department of
Regenerative Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy
La bellezza delle Cellule Staminali
Dr Gianluca Vadalà, MD, PhD
DIPARTIMENTO DI ORTOPEDIA E TRAUMATOLOGIA
DIRETTORE: PROF. VINCENZO DENARO
www.cellfactorymilano.com

stem
cell

What
is
a
stem
cell?

stem
cell

SELF-‐RENEWAL

specialized
cell

e.g.
muscle
cell,
nerve
cell

DIFFERENTIATION

http://www.eurostemcell.org

1
stem
cell

Self
renewal
-‐
maintains

the
stem
cell
pool

4
specialized
cells

DiﬀerenEaEon
-‐
replaces
dead
or
damaged

cells
throughout
your
life

Why
self-‐renew
AND
diﬀeren8ate?

1
stem
cell


Where
are
stem
cells
found?

embryonic
stem
cells

blastocyst
-‐
a
very
early

embryo

Essue
stem
cells

fetus,
baby
and
throughout
life


Tissue stem cells
muscles

skin

surface
of
the
eye

brain

breast

intes;nes
(gut)

bone
marrow

tes;cles


Principles of renewing tissues
Stem
cell

commiIed
progenitors:

-‐ 
“transient
amplifying
cells”

-‐ 
mul;potent

-‐ 
divide
rapidly

-‐ 
no
self-‐renewal

specialized
cells:

-‐ 
work

-‐ 
no
division

Tissue stem cells

Stem
cell
niches

Direct contact Soluble factors Intermediate cell
stem
cell

niche

Niche

Microenvironment
around
stem
cells
that
provides

support
and
signals
regula;ng
self-‐renewal
and

diﬀeren;a;on


Homeostasis

•  The ability to regulate internal conditions,
usually by a system of feedback controls
Stabilize health and functioning, regardless of the
outside changing conditions.
•  One piece of homeostasis is the constant or
periodic generation of new cells to replace
old, damaged, and dying cells
•  Adult stem cells fulfill this role through the
process of regeneration

Mesenchymal stem cells (MSCs)
MSC

bone
marrow

commiIed
progenitors

Bone
(osteoblasts)

Car;lage
(chondrocytes)

Fat
(adipocytes)

specialized
cells

Tissue stem cells

Friedenstein et al. 1968
A.J. Friedenstein is generally credited with the discovery of MSC.
Mesenchymal Stem Cells!
ü  Cells present within the
hematopoietic microenvironment
of bone marrow
ü  spindle-shaped cells (fibroblastic-
like) after plastic attachment
ü  capacity to form colonies (colony
forming unit-fibroblast, CFU-F)

Pittinger, Science 1999
hMSC
human Skin
fibroblast
Oil red O Immunostaining for Coll II alkaline
phosphatase
differentiation capacity of MSCs!

Sacchetti, Cell 2007
Self renewal of MSC!
MSCs have been identified as sinusoidal
adventitial reticular cells

Mesenchymal Stem/Stromal Cells (MSC)
osteocyte
chondrocyte
miocyte
tenocyte
adipocyteStromal cells
Growth factor &
Cytokine
Differentiation
Trophic effect
Proliferation
Anabolism
Reparative activity
Anti-inflammation
Pittenger 1999
Caplan 2006
Tissue regeneration mechanisms!

MSCs function for tissue regeneration
Microenvironment

Regenerate
Trophic

BioacEve
Factors

Immuno-‐

suppressive

Reserve
Cells

Turnover
/

Maintainance

MSCs

Caplan & Dennis, J. of Cellular Biochemistry, 1998

Joint and Cartilage
Large bone gap
Tendon lesions
Spine
Regenerative medicine in Orthopaedic

The Intervertebral disc!
Intervertebral
disc
Spinal
segment
Nucleus
Pulposus
Anulus
Fibrosus
Spinal
cord
Nerve
rout

Intervertebral disc degeneration!
Degenerative cascade

Therapeutic hypothesis
Differentiation
H20 H20
H20
H20 H20
Collagen
Proteoglycans
Stem cells
to supplement disc cell population of a degenerated
disc by stem cell transplantation

Preliminary study
Evaluation of the interaction between
Mesenchymal Stromal/Stem Cells from bone
marrow and Nucleus Pulposus Cells

Mechanisms of interction ?!
Vadalà et al. Spine 2008
MSC
NPC
Co-coltura - 2 wks
Cell sorting
Analysis of gene
expression profile
Double labeling cell system
Alginate beads

Clinical translation

Università Campus Bio-Medico
Unità di Ortopedia e Traumatologia
Vincenzo Denaro, MD
Gianluca Vadalà, MD, PhD
Maria Musumeci,PhD
Fabrizio Russo, MD
Antonino Giacalone, MS
Caterina Cattani, MS
University of Pittsburgh
Stem Cell Research Center
Johnny Huard, PhD
Spine Research Laboratory
James D. Kang, MD
Nam Vo, PhD
Gwen Sowa, MD, PhD
Kevin Bell, PhD
AO Research Institute Davos
Musculoskeletal Regeneration
Program
Mauro Alini, PhD
Marianna Peroglio, PhD
Matteo D’Este, PhD
Università di Padova
Department of Veterinary Surgery
Roberto Busetto, DVM
Marco Bernardini, DVM
Francesca De Strobel, DVM
Fondazione IRCCS Ca’ Granda, Ospedale
Maggiore Policlinico Milano
Cell Factory
Rosaria Giordano, MD
Lorenza Lazzari, PhD
Acknowledgments

Acknowledgments
Finanziamento PRIN
Stem Cell Research Group
Finanziamento Giovani Ricercatori
Research Traveling fellowship
AOSpine Europe Young Researcher Award

Grazie!
www.unicampus.it

Gianluca Vadalà, La bellezza delle cellule staminali (Msc and art)

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