regenerative therapies for heart and vessels - prof. piotr musiałek
TRANSCRIPT
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Przeszczepiać -czy- Regenerować ?
Klinika Chorób Serca i Naczyń CMUJSzpital im. Jana Pawła II
Krakow
Regenerative Therapies for Heart &Vessels
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WHY ?
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10-year survival in fai lure
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www.poltransplant.org.pl
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www.poltransplant.org.pl
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www.poltransplant.org.pl
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10-year survival in PAD
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Amputations in PAD(Poland)
10 000 / year
1 leg / hour
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THE NEED
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THE NEEDexisting
state-of-the-art therapiesare greatly insuficient
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FEASIBLE ?
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1. ‘post-mitotic’ organ(s)
2. in all mammals... HEALINGis naturally biased towardsFIBROTIC SCAR formation
FEASIBILITY ?
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Cardiac & Vascular regeneration therapy in 2014...
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but...
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Cardiac & Vascular regeneration therapy in 2014...
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Cardiac & Vascular regeneration therapy in 2014...
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Cardiac & Vascular regeneration therapy in 2014...
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‘post-mitotic organ ’
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The heart is NOT a post-mitotic organ
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The heart is NOT a post-mitotic organ
+ A P O P T O S I S !
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2001
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Bone marrow – mediated endogenous ‘pro-regenerative’ resposne after AMI
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Bone marrow – mediated endogenous ‘pro-regenerative’ resposne after AMI
SDF expression in infarct zone
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Optimal cell type and dose ?
Myocardial regeneration therapy in 2014+
Jagiellonian University Dept. of Cardiac & Vascular DiseasesJohn Paul II Hospital
Krakow
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Intrinsic cardiac stem cells
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10 years
Jagiellonian University Dept. of Cardiac & Vascular DiseasesJohn Paul II Hospital
Krakow
+
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How to (best)deliver the cells?
Myocardial regeneration therapy in 2014+
Jagiellonian University Dept. of Cardiac & Vascular DiseasesJohn Paul II Hospital
Krakow
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DEVICE
Optimized retention
Hom
ing
signa
ls
Cell f
unct
iona
lity
Cell a
dhes
ion
Mat
rices
Surv
ival
TISSUE
BIOLOGICS
Injection method & techniqueNeedle designInjection speedTissue-device compatibility
Biocompatibility
Cell concentration
Viscosity
Stability
Adapted from J. Bartunek et al. Clinical Pharm & Ther 85, 548-552
Development
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Labeled cells (SPECT) and cMRI: I M A G E F U S I O N
P Banyś 2010-2012
Labeled CD34+ cells (3D SPECT)
myocardialCD34+
uptake
(part of) CD34+ liver uptake
Obrazowanie hybrydowe: zawał (MRI) / komórki (SPECT)
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P. Musiałek and Team Circulation: Cardiovasc Img 2013
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Infarct Size (not LVEF) Determines Cell Uptake
P. Musiałek and Team Circulation: Cardiovasc Img 2013
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TERAPIA KOMÓRKOWA zawału: stan wiedzy (2013) PTK
2012
INCREASE IN LVEF @ 6mo
Zimmet Eur J Heart Fail 2012* przezwieńcowe podanie komórek
*
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Biocompatible scaffolds
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Biopatches for IPCs
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• CE Mark since April 2012• Available on the market
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Needle design based on mathematical modelingVariable caliber and distribution of infusion holes: Drug Product is more evenly distributed along the needle extremity Enhanced fluid distribution inside myocardium
Development
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transendocardial
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Critical Limb Ischaemia
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Critical Limb Ischaemia
variable (naturally) disease progression rate
concomittant revasculatization of the feeding vessel(s)
other confounders (such as exercise – proangiogenic)
.
.
.
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Novel Off-shelfRegenerative Cell Application in Treatment
of No-option Critical Limb Ischemia
email: [email protected]
INVESTIGATOR – INITIATED STUDY
Mariusz TRYSTUŁA, Marcin MAJKA (PIs)
Jagiellonian University Dept. of Cardiac & Vascular Surgery and Transplantation at John Paul II Hospital
and Jagiellonian University Dept. of TransplantationKrakow
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Stem cell – cased therapeutic strategies
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Cardiac & Vascular regeneration therapy in 2014...
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Cardiac & Vascular regeneration therapy in 2014...
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Cardiac & Vascular regeneration therapy in 2014...
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