Przeszczepiać -czy- Regenerować ?
Klinika Chorób Serca i Naczyń CMUJSzpital im. Jana Pawła II
Krakow
Regenerative Therapies for Heart &Vessels
WHY ?
10-year survival in fai lure
www.poltransplant.org.pl
www.poltransplant.org.pl
www.poltransplant.org.pl
10-year survival in PAD
Amputations in PAD(Poland)
10 000 / year
1 leg / hour
THE NEED
THE NEEDexisting
state-of-the-art therapiesare greatly insuficient
FEASIBLE ?
1. ‘post-mitotic’ organ(s)
2. in all mammals... HEALINGis naturally biased towardsFIBROTIC SCAR formation
FEASIBILITY ?
Cardiac & Vascular regeneration therapy in 2014...
but...
Cardiac & Vascular regeneration therapy in 2014...
Cardiac & Vascular regeneration therapy in 2014...
Cardiac & Vascular regeneration therapy in 2014...
‘post-mitotic organ ’
The heart is NOT a post-mitotic organ
The heart is NOT a post-mitotic organ
+ A P O P T O S I S !
2001
Bone marrow – mediated endogenous ‘pro-regenerative’ resposne after AMI
Bone marrow – mediated endogenous ‘pro-regenerative’ resposne after AMI
SDF expression in infarct zone
Optimal cell type and dose ?
Myocardial regeneration therapy in 2014+
Jagiellonian University Dept. of Cardiac & Vascular DiseasesJohn Paul II Hospital
Krakow
Intrinsic cardiac stem cells
10 years
Jagiellonian University Dept. of Cardiac & Vascular DiseasesJohn Paul II Hospital
Krakow
+
How to (best)deliver the cells?
Myocardial regeneration therapy in 2014+
Jagiellonian University Dept. of Cardiac & Vascular DiseasesJohn Paul II Hospital
Krakow
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
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)
P. Musiałek and Team Circulation: Cardiovasc Img 2013
Infarct Size (not LVEF) Determines Cell Uptake
P. Musiałek and Team Circulation: Cardiovasc Img 2013
TERAPIA KOMÓRKOWA zawału: stan wiedzy (2013) PTK
2012
INCREASE IN LVEF @ 6mo
Zimmet Eur J Heart Fail 2012* przezwieńcowe podanie komórek
*
Biocompatible scaffolds
Biopatches for IPCs
• CE Mark since April 2012• Available on the market
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
transendocardial
Critical Limb Ischaemia
Critical Limb Ischaemia
variable (naturally) disease progression rate
concomittant revasculatization of the feeding vessel(s)
other confounders (such as exercise – proangiogenic)
.
.
.
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
Stem cell – cased therapeutic strategies
Cardiac & Vascular regeneration therapy in 2014...
Cardiac & Vascular regeneration therapy in 2014...
Cardiac & Vascular regeneration therapy in 2014...