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 adipocyte Stromal 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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