This document discusses regenerative therapies for the heart and vessels. It notes the need for new therapies as existing treatments are insufficient. Regenerative therapies using cells are feasible, though delivery methods need optimization. Studies have shown bone marrow cells can help endogenous repair after a heart attack. Intrinsic cardiac stem cells may be an optimal cell type. Imaging has shown stem cell uptake in the heart after injection. Further research is still needed to determine the best cell type, dose, and delivery method for myocardial regeneration therapies. The document also discusses a proposed study on regenerative cell therapy for critical limb ischemia.

1. Regenerative Therapies for Heart &Vessels
Przeszczepiać -czy- Regenerować ?
Klinika Chorób Serca i Naczyń CMUJ
Szpital im. Jana Pawła II
Krakow

2. WHY ?

3. 10-year survival
in failure

5. www.poltransplant.org.pl

6. www.poltransplant.org.pl

7. www.poltransplant.org.pl

9. 10-year survival
in PAD

10. Amputations in PAD
(Poland)
10 000 / year
1 leg / hour

11. THE NEED

12. THE NEED
existing
state-of-the-art therapies
are greatly insuficient

13. FEASIBLE ?

14. FEASIBILITY ?
1. ‘post-mitotic’ organ(s)
2. in all mammals... HEALING
is naturally biased towards
FIBROTIC SCAR formation

15. Cardiac & Vascular regeneration therapy in 2014...

17. but...

18. Cardiac & Vascular regeneration therapy in 2014...

19. Cardiac & Vascular regeneration therapy in 2014...

20. Cardiac & Vascular regeneration therapy in 2014...

21. ‘post-mitotic organ ’

22. The heart is NOT a post-mitotic organ

23. The heart is NOT a post-mitotic organ
+ A P O P T O S I S !

24. 2001

25. Bone marrow – mediated endogenous
‘pro-regenerative’ resposne after AMI

26. Bone marrow – mediated endogenous
‘pro-regenerative’ resposne after AMI
SDF expression in infarct zone

27. Myocardial regeneration therapy in 2014+
Optimal cell type
and dose ?
Jagiellonian University Dept. of Cardiac & Vascular Diseases
John Paul II Hospital
Krakow

29. Intrinsic
cardiac stem cells

31. 10 years
Jagiellonian University Dept. of Cardiac & Vascular Diseases
John Paul II Hospital
Krakow
+

46. Myocardial regeneration therapy in 2014+
How to (best)
deliver the cells?
Jagiellonian University Dept. of Cardiac & Vascular Diseases
John Paul II Hospital
Krakow

47. DEVIC
E
Development
Optimized
retention
Homing signals
Cell functionality
Cell adhesion
Matrices
Survival
TISSU
E
BIOLOGIC
S
Injection method & technique
Needle design
Injection speed
Tissue-device compatibility
Biocompatibility
Cell concentration
Viscosity
Stability
Adapted from J. Bartunek et al. Clinical Pharm & Ther 85, 548-552

55. Labeled cells (SPECT) and cMRI: I M A G E F U S I O N
P Banyś 2010-2012
Obrazowanie hybrydowe:
zawał (MRI) / komórki (SPECT)
Labeled CD34+ cells
(3D SPECT)
myocardial
CD34+ uptake
(part of) CD34+ liver uptake

56. P. Musiałek and Team Circulation: Cardiovasc Img 2013

57. Infarct Size (not LVEF) Determines Cell Uptake
P. Musiałek and Team Circulation: Cardiovasc Img 2013

60. TERAPIA KOMÓRKOWA *
zawału:
stan wiedzy (2013) PTK
2012
INCREASE IN LVEF @ 6mo
Zimmet * przezwieńcowe podanie komórek Eur J Heart Fail 2012

63. Biocompatible scaffolds

64. Biopatches for IPCs

68. • CE Mark since April 2012
• Available on the market

69. Development
Needle design based on mathematical modeling
Variable caliber and distribution of infusion holes: Drug Product
is more evenly distributed along the needle extremity 
Enhanced fluid distribution inside myocardium

71. transendocardial

75. Critical Limb Ischaemia

76. Critical Limb Ischaemia
variable (naturally) disease progression rate
...
concomittant revasculatization of the feeding vessel(other confounders (such as exercise – proangiogenic)

82. INVESTIGATOR – INITIATED STUDY
Novel Off-shelf
Regenerative Cell Application in Treatment
of No-option Critical Limb Ischemia
Mariusz TRYSTUŁA, Marcin MAJKA (PIs)
email: mrt@onet.pl
Jagiellonian University Dept. of Cardiac & Vascular Surgery
and Transplantation at John Paul II Hospital
and Jagiellonian University Dept. of Transplantation
Krakow

83. Stem cell – cased therapeutic strategies

86. Cardiac & Vascular regeneration therapy in 2014...

87. Cardiac & Vascular regeneration therapy in 2014...

88. Cardiac & Vascular regeneration therapy in 2014...