Detailed about delivery approaches of stem cells to the heart.

1. Biomaterials as Stem Cell Niches for Cardiac
Cell Therapy
Rashedul Islam
M Sc. Student
Dept. of
Biotechnology and Genetic Engineering
Jahangirnagar University, Savar, Dhaka
Bangladesh.

2. • Cardiac cell therapy
• Possible cells for cardiac cell therapy
• Delivery methods of stem cells
• Limitations
• Biomaterials as scaffold for cardiac cell therapy
• Conclusion
Outline of the presentation

3.  Therapy for myocardial infarction and heart failure.
 Aims to restore the functionality of the diseased or injured
myocardium using stem/progenitor cells.
The key elements are:
 the choice of donor cell, the strategy of delivery and the
understanding of the mechanisms.
Issues with human embryonic stem cells:
 Immunogenicity
 Tumorigenesis
 Ethical challenges
Cardiac Cell Therapy

4.  A variety of cell types have been tested for acute myocardial
infarction and chronic heart failure.
 Autologous cell sources: Adult bone marrow derived stem
cells and skeletal-muscle derived myoblasts.
Skeletal-muscle derived myoblasts?
 Reported with ventricular arrhythmias.
Bone marrow-derived stem cells?
 Significantly increase global or regional ejection fraction
 Reduce infarct size and end systolic volumes in patients with
acute myocardial infarction
 Autologous, thus eliminates the need for immunosuppression
 Circulating endothelial progenitor cells, or tissue-residing stem
cells improved neovascularization and cardiac function.
What types of cells could be used?

6. 1. Intramyocardial injection
2. Intracoronary injection
3. Intravenous injection and
4. Chemotactic mobilization
Delivery Strategies for Cardiac Cell Therapy

7. • Direct injection of stem cells in myocardium.
• Injections are most frequently made into the left ventricle by direct
epicardial approach or using a catheter-based transendocardial
approach.
A. Epicardial injection:
• Injection process is simple and considered as the most reliable
delivery method.
Advantages:
• Higher cell retention within the myocardium.
• Requires fewer cells to achieve engraftment compared with
intracoronary or intravenous injection.
Disadvantage:
• This invasive delivery is associated with intraoperative and
postoperative risks.
• Increase the risk of cardiac arrhythmias or require the use of anti
arrhythmic agents
1. Intramyocardial injection

8. B. Transendocardial injection:
• An improved approach for intramyocardial injection is to
implant stem cells.
• Utilizes a percutaneous catheter-based approach.
• For example, NOGATM system uses a percutaneous catheter
guided by left ventricular electromechanical mapping to implant
stem cells.
Advantages
• This system allows for injection with high precision into
nonviable areas of the myocardium with an injection-needle
catheter, which offers an advantage over the more invasive
surgical approach and its associated risks.
• Can be repeated if needed.
1. Intramyocardial injection

9. • A percutaneous transluminal coronary catheter used for
intracoronary delivery of bone marrow-derived stem cells after
myocardial infarction.
Advantages:
• It can deliver the maximum concentration of cells to the site of
infarct and peri-infarct tissue.
• Allows the stem cells to ‘‘home to’’ and incorporate in the
areas bordering the infarct zone in a homogenous manner.
• Thus no ‘islands’ of cells in the infarcted myocardium.
Disadvantage:
• May lead to decreased blood flow which could cause ischemia
leading to arrhythmia.
2. Intracoronary injection

10. • Intravenous injection obviates the need for cardiac surgery or
cardiac catheterization.
• Heavily depends on homing signal and homing mechanisms.
• It is thought that, micro-environmental factors, expression of
matrix and adhesion molecules by injured tissue, homing
receptors and various factors relating to migration are involved
in the homing process of stem cells.
Advantages:
• Least invasive
Disadvantages:
• Due to long circulation time, cells could be lost by extraction
towards non-cardiac organs and fail to home to the area of
infarct.
• Consequently, a large dose of stem cells may be needed to get
enough cells reach to the heart compared with other delivery
3. Intravenous injection

11. Bodo E. Strauer, and Ran Kornowski Circulation.
2003;107:929-934
Copyright © American Heart Association, Inc. All rights reserved.
Delivery options for stem cell transfer modalities
to the heart.

12. • The homing of stem cells has been
performed via local delivery of various chemotactic
factors
• Homing factor, stromal derived factor 1 alpha (SDF-1α)
demonstrated enhanced recruitment of c-kit+ stem cells
to myocardium in a mouse infarct model.
• It was correlated with increased ejection fraction and
fractional shortening determined by echocardiography.
4. Chemotactic Mobilization

13. doi: 10.1161/01.ATV.0000073832.49290.B5

14. Regardless the application methods, other limitations are-
• Majority of transplanted cells die within the first days
post-transplantation and the long term engraftment rate
is very low.
• The main factor contributing to cell death is that the
areas where stem cells are transplanted to are ischemic
regions.
Solution:
• Biomaterial scaffolds for cardiac cell therapy .
Limitations

15. • A tissue-engineering approach to achieve myocardial
regeneration by implanting cells into a scaffold onto the surface
of the heart.
• The scaffold served as a temporary stem cell niche to maintain
the proliferation and differentiation of the transplanted stem cells.
• A fibrin patch with porcine mesenchymal stem cells to the LV
anterior wall of swine LV myocardial infarction models were
transplanted.
• The results indicated this fibrin-MSC patch may prevent LV wall
thinning and rescue myocardial function.
• Another novel approach is PEGylated fibrin biomatrix using a
dysfunctional, amine reactive PEG.
• This system was designed to realize a combination strategy
which aims to facilitate myocardium regeneration after
myocardial infarction by delivering both stem cells and growth
factors to the injured myocardium.
Biomaterial scaffolds for cardiac cell therapy

17. • Although stem cell therapy is reported as efficacious, the
underlying mechanism remains unclear and there is significant
opportunity to improve clinical outcomes.
• Stem cells may improve cardiac function by trans-
differentiating into endothelial cells or cardiomyocytes, by
promoting angiogenesis and improving myocardial blood flow,
or by paracrine effects.
• More efficient delivery method and localization are strongly
required.
• Engineering appropriate interaction between biomaterials and
cells can increase both delivery efficiency and appropriate
localization to the injured sites, thus reducing high dose
requirements and improving the cells functions.
Conclusion

18. Thank you