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: mrt@onet.pl

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...