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. |