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Le nuove frontiere
della medicina rigenerativa
I SISTEMI AUTOMATIZZATI
Biella, 5 giugno 2009
Biella, 5 giugno 2009
Platelets
play an important
role in mechanisms
of tissue repair
Biella, 5 giugno 2009
Platelets
Anucleated cells derived from
fragments of megakaryocites
 Normal
value
in
peripheral
blood:150-400x103/uL
 Half life in peripheral blood: 8-10
days

Biella, 5 giugno 2009
Platelets contain  granules that
act as repairing factors
receptorial mechanisms
PDGF (Platelet derived growth factor):
– mitogenic and angiogenic
– up-regolation of different ripairing factors
Biella, 5 giugno 2009
Platelets contain  granules that
act as repairing factors
receptorial mechanisms
TGF- (Transforming growth factor beta):
– Fibroblasts and pre-osteoblasts
stimulation,
– Inhibition of bone reabsortion
– chemotaxis
Biella, 5 giugno 2009
Platelets contain  granules that act as repairing factors
receptorial mechanisms
EGF (Epidermal
growth factor):
Mesenchimal and epidermal cell stimulation
VEGF (Vascular
endothelial growth factor):
Endothelial cell stimulation
IGF I-II
(Insulin like factors):
Osteoblasts increment
Stimulation of bone deposition
Biella, 5 giugno 2009
Recombinant PDGFs
Natural PDGFs
•Engineered growth factor
Autologous
Allogeneic
•(Bone Morphogenetic Proteins)
•OP-1- BMP7 (Osteogenic
Protein-1)
•BMP-2 ( InductOs )
•rhBMP-2(INFUSETM)
•rhPDGF BB (Regranex) ?
Biella, 5 giugno 2009
Natural PDGFs:
topical use
Autologous
Allogeneic
Biella, 5 giugno 2009
Platelet gel:
a new blood component
PRP and PPP
Platelet aggregates
and fibrin glue
Biella, 5 giugno 2009
Platelet gel

Manual
 Automatic
preparation
Biella, 5 giugno 2009
Platelet gel

Automatic
method
–
–
–
–

Asepsis
Reproducibility
High speed
Real time
availability
– Costs?
Manual method
– Risk of
contamination
– Operator
dependent
– Time consuming
– Costs?
Biella, 5 giugno 2009
Automatic method (1)
Lost of platelets during
manipulation
 High variation in growth factors
concentration
 Small volume of blood required
(27 – 110 ml)
 High efficiency in collecting and
concentrating platelets

Biella, 5 giugno 2009
Automatic method (2)
High platelet recovery during
manipulation
 Live platelets
 No leucocyte degranulation (low
levels of MPO)
 Antimicrobial properties of Platelet
Gel at the site of application (with
low levels of MPO)

Biella, 5 giugno 2009
Automatic method (3)
High variation in growth factor
concentration
 The content of growth factors in
PRP can vary, depending on the
system used for the preparation

Biella, 5 giugno 2009
Automatic technique (1)
Biella, 5 giugno 2009
Automatic technique (2)
Biella, 5 giugno 2009
Preparazione del PRP
Preparazione del crioprecipitato ricalcificato
Unione del crioprecipitato
ricalcificato e del PRP
Gel piastrinico
Biella, 5 giugno 2009
Platelet gel
Drug delivery system
Biella, 5 giugno 2009
Indications of growth factors in
upper limb traumatology
Any time you need an
accellerated repair process
under strict controlled trials
Biella, 5 giugno 2009
Factors influencing PDGFs
levels
WBC
 Circulating plasmatic growth
factors
 Fibrin clot and PDGFs incorporation
 Adequate platelet activation

Biella, 5 giugno 2009
PDGFs
natural vs recombinant



Autologous
product
All factors
administered
Relatively low
costs


Exogenous product
(autoimmunity,
tissue degeneration)
Side effects
(fever,infections,pain,
amilasemia)


Only one factor
administered
Very high costs
Biella, 5 giugno 2009
Auto vs Allo
Autologous
Allogeneic
patient’s own tissue
no immune response
donor priming
immune response
No Ethical Concerns
- Less Manipulation
-
less risk
less time
less cost
Ethical Concerns
• More manipulation
-
Biella, 5 giugno 2009
more risk
more time
more cost
Platelet gel: problems
Optimal dose
 Randomized clinical trials
 Role of contaminant WBC
 Fresh vs frozen gel

Biella, 5 giugno 2009
FUTURE GOALS
PDGFs +
Mesenchimal stem cells
Biella, 5 giugno 2009
Fondazione IRCCS Policlinico
S.Matteo – Pavia
Servizio di Immunoemaologia e
Trasfusionale







Cesare Perotti
Gianluca Viarengo
Claudia Del Fante
Paola Bergamaschi
Andrea Marchesi
Valeria Genovese
Bina Romano

Laura Salvaneschi
Biella, 5 giugno 2009