Revista nº 809

Ruiz-de-Almirón Ingeniería tisular del miocardio · 41 · Actualidad Médica · Número 809 · Enero/Abril 2020 Páginas 39 a 47 or biological matrices and cardiac cells to replace the diseased myocardium in vivo . Tissue must restore basic cardiac functions as well as functional vascularization (26). In addition to the cell type, scaffold and bioactive molecules, consideration should be given to the bioreactor where the artificial tissue is grown under controlled conditions (3). Thus, the ideal construct should be contractile, allowing physiological electrical propagation, me- chanically robust, but flexible, vascularized or capable of rapid vascularization after implantation, non-inmunogenic and with good biodegradability (3,27). Currently researches are addressing different methods of tissue engineering: biomimetic scaffolds, hydrogels, decellulari- zed scaffolds and cell sheets. All of them are trated below. a) Biomimetic scaffolds A biomimetic biomaterial can be any scaffolding material that mimics the characteristics of the natural ECM. They are ba- sed on polymers that may be natural, synthetic or biosynthetic (26,28). They are interesting for the repair and regeneration of tissues due to their biodegradability, mechanical properties or high porosity. Porosity is it very important in terms of structure functionality because it allows cell infiltration and colonization of the extracellular matrix improving cell growth, proliferation and migration, as well as efficient cell adhesion and diffusion, tissue vascularization and tissue formation. So, scaffolds should allow the transport of the nutrients needed to the cell attachment, proliferation and differentiation, stimulation of cell-biomaterial CELL ADVANTAGES DISADVANTAGES REF. SOURCE Fetal CMs Potential integration and regeneration Ethical issues, limited avaibility and immunogenicity. Long-term studies revealed massive cell death and limited proliferation of the implanted cells . 12 Allogeneic Umbilical Cord- Derived MSCs Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs No severe adverse effects were observed, but preliminary results, need to be confirmed in larger and more organized clinical trials 13,14 Allogeneic Embryonic cells Pluripotent, It has been demonstrated in a non-human primate model that an intramyocardial delivery of human ESC- derived CMs gave re-muscularization of the infarcted zone Ethical and legal issues. Adverse arrhythmic complications 15,16 Allogeneic AdSCs Preclinical studies with AdSCs have shown improvement in ventricular function in animal models of MI. Clinical trials in humans showed only modest beneficial effects on cardiac function and on myocardial perfusion Low survival 3,17 Autologous Skeletal myoblast Positive outcomes by reducing infarct size, as well as myocardial fibrosis, thwarting ventricular remodeling and improving overall cardiac function. Ventricular arrhythmias 18 Autologous BMD stem cells Increase of the mean global left ventricle ejection fraction. Significant differences among the trials. The differences made a reliable comparison of the trials’ outcome and also the reproducibility. 14,19 Autologous hiPSCs In vivo transplantation experiments with hPSC-CMs have been showed promising effects of heart regeneration, like progressive maturation and generate remuscularization of infarcted heart Ventricular arrhythmias observed in transplanted large animals 20 Autologous Cardiac Stem Cells (CSCs) Cardiosphere-derived cells have been shown their ability to promote cardiac regeneration, reducing the scar size and thickening the wall of the infarcted zone in a clinical trial. Limited avaibility. The real regenerative potential remains controversial. 21 Autologous Table 1. Stem cells types used for cardiac tissue engineering AdSCs: Adipose stem cells-based; BMD: bone marrow-derived stem cells; ESC-derived Cms: Embryonic-stem-cell-derived cardiomyocytes; Fetal Cms: Fetal cardiomyocytes; hiPSCs: human induced pluripotent stem cells; hPSC-CMs: human pluripotent stem cells derived cardiomyocytes; LVEF: left ventricular ejection fraction MI: miocardial infartion; UC-MSCs: Umbilical cord Mesenchymal Stem Cells (1,3,12-21).