I
Home Purpose Aims and Goals Strategies Limitations and Future Directions

 

 

Cell sources for myocardial tissue engineering

The optimal cell source to create a tissue-engineered cardiac muscle construct would be easy to harvest, unlimited, proliferate in large numbers, autologous and has the ability to differentiate into mature, functional cardiomyocytes but no such cell source currently exists. Thus, the choices of cell source and composition of cells in these constructs are important aspects in cardiac tissue engineering. The native myocardium consists of cardiac myocytes, endothelial cells, fibroblasts, smooth muscle cells, neural cells, and leukocytes. The exact distribution of each cell type in the tissue has not been determined but it suggests that a true cardiac muscle construct requires cardiac myocytes and non-myocytes.

Several cell sources have been used : ( Leor, et al. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacology & Therapeutics 2005; 105: 151-163 and Zammaretti P and Jaconi M. Cardiac tissue engineering: regeneration of the wounded heart. Current Opinion in Biotechnology 2004, 15: 430-434.)

Fetal cardiomyocytes
Embryonic stem cells and embryonic stem cell-derived cardiomyocytes
Stem cells of different types
Skeletal muscle cells
Bone marrow cells
Umbilical cord cells
Mesenchymal stem cells
Smooth muscle cells
Endothelial progenitor cells
Fibroblasts
Monocytes
Aortic valve interstitial cells
Cloned cells by therapeutic cloning

The following table describes the advantages and disadvantages of various cell sources. ( Leor, et al. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacology & Therapeutics 2005; 105: 151-163)

 

Autologous

Easily Obtainable

Highly expandable

Cardiac myogenesis

Clinical experience

Safety Concerns

Fetal cardiomyocytes

No

No

No

Yes

No

No

Embryonic stem cells

No

No

Yes

Yes

No

Yes teratoma

Skeletal myoblasts

Yes

Yes

Depends on age

Debated

Yes

Yes, arrhythmias

Bone marrow cells

Yes

Yes

Depends on age

Debated

Yes

Yes, calcification

Mesenchymal stem cells

Yes

No

Depend on age

Yes

No

Yes Fibrosis calcification

Hematopoietic stem cells

No

Yes

Yes

Debated

Yes

No

Fibroblasts

Yes

Yes

Yes

No

No

No

Smooth muscle cells

Yes

Yes

Yes

No

No

No

In theory, cardiomyocytes would be the ideal donor cell type because they have the natural electrophysiological, structural and contractile properties desired. However, they are difficult to obtain, to expand, and not autologous. Currently, the most used cell sources are skeletal myoblasts and bone marrow cells. Stem cells seem to be the most promising cell sources because they are undifferentiated and capable of self-renewal. Embryonic stem cells are attractive because they have unlimited differentiation capacity and indefinite propagation. However, they are allogenic, have the potential to form tumors, low efficiency of differentiation into cardiomyocytes, and have ethical issues. Adult stem cells would theoretically be the ideal choice since they are autologous, no ethical issues, unlikely tumor formation, many potential sources, and high plasticity. However, much more research needs to settle controversial data on stem cells and an efficient and reproducible method is needed to control and direct differentiation of stem cells to the desired cell type.

 

Copyright 2006 Anh Huynh All Rights Reserved