401 research outputs found
Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair
No full textThe heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome ( for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application
Embryonic and embryonic-like stem cells in heart muscle engineering
No full textCardiac muscle engineering is evolving rapidly and may ultimately be exploited to (1) model cardiac development, physiology, and pathology; (2) identify and validate drug targets; (3) assess drug safety and efficacy; and (4) provide therapeutic substitute myocardium. The ultimate success in any of these envisioned applications depends on the utility of human cells and their assembly into myocardial equivalents with structural and functional properties of mature heart muscle. Embryonic stem cells appear as a promising cell source in this respect, because they can be cultured reliably and differentiated robustly into cardiomyocytes. Despite their unambiguous cardiogenicity, data on advanced maturation and seamless myocardial integration of embryonic stem cell-derived cardiomyocytes in vivo are sparse. Additional concerns relate to the limited control over cardiomyogenic specification and cardiomyocyte maturation in vitro as well as the risk of teratocarcinoma formation and immune rejection of stem cell implants in vivo. Through the invent of embryonic-like stem cells - such as parthenogenetic stem cells, male germline stem cells, and induced pluripotent stem cells - some but certainly not all of these issues may be addressed, albeit at the expense of additional concerns. This review will discuss the applicability of embryonic and embryonic-like stem cells in myocardial tissue engineering and address issues that require particular attention before the potential of stem cell-based heart muscle engineering may be fully exploited. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited". (C) 2010 Elsevier Ltd. All rights reserved
Remuscularization of the failing heart
No full textMyocardial remuscularization can be achieved by cardiomyocyte implantation. Electromechanical integration and long‐term survival of cardiomyocyte grafts are essential for maximal therapeutic impact. Cardiomyocyte application with support material has been instrumental in enhancing cell retention. Co‐administration of pro‐survival factors and immunological matching are additional strategies for increased cell graft survival. Finally, larger cardiomyocyte grafts, although therapeutically desirable, will increase the risk for arrhythmias and, if pluripotent stem cells are used to derive cardiomyocytes, tumour formation. This review introduces major challenges pertaining to myocardial remuscularization (cardiomyocyte retention, arrhythmogenicity and tumourigenicity), discusses studies addressing these challenges, and suggests strategies to overcome remaining challenges for the translation of myocardial remuscularization
Remuscularizing Failing Hearts with Tissue Engineered Myocardium
No full textSupporting or even replacing diseased myocardium with in vitro engineered heart muscle may become a viable option for patients with heart failure. The key to success will be to (1) generate human heart muscle equivalents in vitro, (2) integrate the latter into a failing heart, (3) ensure long-term functional competence of the grafts, and (4) prevent unwanted effects including arrhythmias, inflammation/rejection, and tumor formation. Several promising tissue engineering technologies have already been developed and are presently being tested in animal models. The rapidly evolving field of human stem cell biology has in parallel identified unique cell sources of potential clinical relevance. Somatic cell reprogramming and nontransduced, nonembryonic pluripotent stem cells may be of particular interest to eventually provide patient-specific cells and tissues. Yet, limited cardiac differentiation and cell immaturity still restrict a broad application of any stem cell type in cardiac muscle engineering. Bioreactor technologies, transgenic "optimization,'' and growth factor, as well as physical conditioning, have been used to address these caveats. This review summarizes different tissue engineering modalities, speculates on potential clinical uses, provides an overview on cell sources that may ultimately facilitate a patient-specific application, and discusses limitations of tissue engineering-based myocardial repair. Antioxid. Redox Signal. 11, 2011-2023
Translating Myocardial Remuscularization
No full textMyocardial remuscularization can be achieved by the implantation of cardiomyocyte-containing grafts. Critical steps toward clinical translation of the first generation cardiac remuscularization therapies include the choice of animal models with high predictive validity for therapeutic outcome in clinical trials
Individualized stem cell therapy
No full textStem cells are attributed with having a great potential in regenerative medicine. Pluripotent stem cells are particularly interesting because they can be multiplied indefinitely and also differentiated under defined conditions. Currently, cardiomyocytes can be differentiated very effectively from pluripotent stem cells, making the former an attractive starting material for cardiac disease modeling in a culture dish (patient in a dish) and cell based-therapy in heart failure. The rapid biotechnological advances made in recent years now enable these concepts to be translated into clinical applications
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