The discoveries in the research of stem cell properties have transformed approach to the treatment of multiple diseases. Nowadays, several types of stem cells are distinguished – totipotent, pluripotent, unipotent, etc. – and they all differ in their capacity to differentiation and proliferation. The investigation of adult stem cells and induced pluripotent stem cells is of increasing interest as these cells have the most potential for the restoration of myocardial infarction-induced tissue damages. The application of cell-based therapy in the treatment of cardiac disorders is underinvestigated, but the recent clinical research findings already reveal some promising results.
It is possible to define stem cells as the structures capable of transforming into functionally active cells. A stem cell can grow into a hepatocyte, a nephrocyte, a cardiomyocyte, etc. (Kin et al., 2013). By their nature, stem cells serve as reserve material needed for the formation of new cells replacing dead or damaged ones.
The main property of any stem cell is its potency which is defined by the level of its differentiation and proliferation (Kin et al., 2013). The potency is the strictly limited cell’s capability to be transformed into particular types of cells. The larger number of cell types can derive from a stem cell, the greater its potency.
For example, fibroblasts can transform into endothelial cells and adipocytes while mesenchymal stem cells can form cardiomyocytes, muscle fibers, etc. (Kin et al., 2013) It means that each stem cell can transform into a limited spectrum of cells which share a set of similar qualities and functions. Based on such limitations in potency, stem cells are divided into totipotent (transforming into all kinds of organ and tissue cells), pluripotent (transforming into several types of organ cells), and unipotent (transforming into cells of one particular organ).
Totipotent Stem Cells (TSCs)
Totipotency is the property of embryonic stem cells that comprise an organism up to the eight-cell stage of embryogenesis. It is impossible to obtain TSCs in the natural conditions and, nowadays, they are cultivated in vitro through artificial fertilization. TSCs are primarily used in animal experiments and organ engineering. Although the first embryonic mouse stem cell was isolated over twenty years ago, there is still no sufficient evidence that their implantation in a human body can be efficient in the treatment of chronic diseases (Krause, Schneider, Jaquet, & Kuck, 2010).
Pluripotent Stem Cells (PSCs)
Embryonic PSCs
PSCs develop at the late phase of embryogenesis when stem cells become “specialized to give rise to only a specific family of cells” (Sharma, Voelker, Sharma, & Reddy, 2012). At the later stages of embryo development, the segregation of primary organ structures and tissues commences. These elementary structures consequently become the basis for the development of all body organs, and evolvement of mesenchymal, neural, blood, and connective tissue PSCs.
Adult PSCs
Throughout the life span, cells of the human body go through life cycles of death and renewal. The restoration of lost cells is possible due to cambial elements – proliferating tissue-specific cell populations in the skin, intestine, muscles, red bone marrow, liver, and brain (Kin et al., 2013). Recently, researchers isolated adults’ cells which are capable of differentiating not only in tissue-specific directions but in the cells of other origins in multiple organs (Kin et al., 2013).
The discovery of adult stem cells helps to take a look at the issues of tissue renewal from a different perspective and change the conception of cellular and genetic therapy. The research of adult PSCs and their impact on recovery processes is one of the most topical tasks, and the significance of research studies in this area is emphasized by the opportunity to use stem cell technologies in the treatment of different cardiac diseases.
Mesenchymal stem cells (MSCs)
MSCs are regarded as the major elements of cell-based therapy. They are pluripotent and can be differentiated into bone, fat, muscle, neural, and other cells. The main source of MSCs is bone marrow but recently they were isolated from subcutaneous adipose tissue and cord blood. The advantage of MSCs’ use in treatment is the opportunity to implant the patient’s genetic material and avoid an adverse immune reaction and rejection of transplant (Sharma et al., 2012).
Cardiac stem cells (CSCs)
Myocardium-derived cellular elements can be differentiated into cardiomyocytes and vascular endothelium (Sharma et al., 2012). Transplantation of such cells in the area of myocardial infarction leads to the development of new cells in the damaged zone. As a result, the organ functions can be substantially restored. However, the methods of CSC isolation are very complex and are associated with the destruction of heart muscular tissue.
Induced PSCs (iPSCs)
Induced PCSs are cultivated from non-pluripotent cells through the process of enforced inducement which implies gene or protein transcription under the influence of particular induction factors and transition of genetic material via viral vectors (Kobayashi, Nagao, & Nakajim, 2013). It is considered that iPSCs are identical to natural PSCs. However, it is observed that the cells cultivated by viral transfection are prone to the occurrence of oncologic diseases (Kobayashi et al., 2013). Therefore, researchers make efforts to find other methods of gene transition needed for the development of healthy stem cells.
Stem Cell Therapy: Acute Myocardial Infarction (AMF)
AMF triggers abrupt discontinuation of the coronary circulation. As a result, irreversible destruction of heart muscle cells occurs. The extent of cell death due to AMF is proportionally correlated with the diameter of an impaired blood vessel in which blood circulation stops. Present-day methods of treatment do not target the loss of tissue caused by AMI, and the researchers consider that bone marrow-derived stem cell treatment can significantly enhance the overall treatment outcomes – improve heart function and delay the progression of disorder (Clifford et al., 2012).
Another group of researchers investigated iPSC-derived cardiomyocytes AMI therapy. Santoso and Yang (2016) found that the iPSC therapy provokes such challenges as low cell survival rate, low level of cell engraftment, and “nonsustained contractility” as well as the difficulties in the monitoring of injected cells’ viability (p. 1).
The common cell delivery techniques are intracoronary stem cell injection and intramyocardial injection. The intracoronary method includes percutaneous transluminal coronary angioplasty and the use of an “over-the-wire balloon with central lumen placed at the desired position” (Sharma et al., 2012). Intracoronary injection of cells is administered up to six times and the surgeons artificially stop blood flow to increase cell retention. The intramyocardial injection is an invasive procedure. However, it is associated with a higher level of organ engraftment (Krause et al., 2010).
It is possible to say that bone marrow-derived stem cell (including MSCs) treatment can be regarded as a better option for AMI intervention because MSCs demonstrate a significant capacity of myocardial repair (Sharma et al., 2012). The meta-analysis of preclinical and clinical studies conducted by Clifford et al. (2012) makes it clear that along with moderate heart function improvement, it is associated with reduced safety concerns although “does not decrease mortality..significantly in the long-term follow-up” (p. 4).
The recent breakthroughs in stem cell research have a positive impact on the development of effective interventions for various diseases. However, despite the great potential of PCS-based therapy in the restoration of myocardium damages, the further investigation of best cell type and best delivery technique issues is needed.
References
Clifford, D. M., Fisher, S. A., Brunskill, S. J., Doree, C., Mathur, A., Clarke, M. J., &… Martin-Rendon, E. (2012). Long-Term effects of autologous bone marrow stem cell treatment in acute myocardial infarction: Factors that may influence outcomes. Plos ONE, 7(5), 1-9. Web.
Kin, T., Pelaez, D., Fortino, V., Greenberg, J., & Cheung, H. (2013). Pluripotent adult stem cells: A potential revolution in regenerative medicine and tissue engineering. In D. Bhartiya & N. Lenka (Eds.), Pluripotent stem cells. Web.
Kobayashi, H., Nagao, K., & Nakajim, K. (2013). Human testis – derived pluripotent cells and induced pluripotent stem cells. Pluripotent Stem Cells. Web.
Krause, K., Schneider, C., Jaquet, K., & Kuck, K. (2010). Potential and clinical utility of stem cells in cardiovascular disease. Stem Cells and Cloning: Advances and Applications SCCAA, 49. Web.
Santoso, M. R., & Yang, P. C. (2016). Magnetic nanoparticles for targeting and imaging of stem cells in myocardial infarction. Stem Cells International, 1-9. Web.
Sharma, R., Voelker, D., Sharma, R., & Reddy, H. (2012). Understanding the application of stem cell therapy in cardiovascular diseases. Stem Cells and Cloning: Advances and Applications SCCAA, 29. Web.