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E. Giacomelli C. L. Mummery M. Bellin 《Cellular and molecular life sciences : CMLS》2017,74(20):3711-3739
Technical advances in generating and phenotyping cardiomyocytes from human pluripotent stem cells (hPSC-CMs) are now driving their wider acceptance as in vitro models to understand human heart disease and discover therapeutic targets that may lead to new compounds for clinical use. Current literature clearly shows that hPSC-CMs recapitulate many molecular, cellular, and functional aspects of human heart pathophysiology and their responses to cardioactive drugs. Here, we provide a comprehensive overview of hPSC-CMs models that have been described to date and highlight their most recent and remarkable contributions to research on cardiovascular diseases and disorders with cardiac traits. We conclude discussing immediate challenges, limitations, and emerging solutions. 相似文献
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A. Beqqali W. van Eldik C. Mummery R. Passier 《Cellular and molecular life sciences : CMLS》2009,66(5):800-813
Studies on identification, derivation and characterization of human stem cells in the last decade have led to high expectations
in the field of regenerative medicine. Although it is clear that for successful stem cell-based therapy several obstacles
have to be overcome, other opportunities lay ahead for the use of human stem cells. A more immediate application would be
the development of human models for cell-type specific differentiation and disease in vitro. Cardiomyocytes can be generated from stem cells, which have been shown to follow similar molecular events of cardiac development
in vivo. Furthermore, several monogenic cardiovascular diseases have been described, for which in vitro models in stem cells could be generated. Here, we will discuss the potential of human embryonic stem cells, cardiac stem
cells and the recently described induced pluripotent stem cells as models for cardiac differentiation and disease.
Received 07 August 2008; received after revision 26 September 2008; accepted 03 October 2008 相似文献
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L. W. van Laake E. G. van Donselaar J. Monshouwer-Kloots C. Schreurs R. Passier B. M. Humbel P. A. Doevendans A. Sonnenberg A. J. Verkleij Christine L. Mummery 《Cellular and molecular life sciences : CMLS》2010,67(2):277-290
Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the
formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found
that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins;
(2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin
expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived
endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted
hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce
the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional
clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells. 相似文献
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The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can be used as an alternative to embryonic cells, and, for the heart at least, these efforts have led to promising results. However, most adult cardiomyocytes are unable to divide and form new cardiomyocytes and would therefore be unable to replace those lost as a result of disease. Basic questions--for example, whether cardiomyocyte replacement or alternatives, such as providing the damaged heart with new blood vessels or growth factors to activate resident stem cells, are the best approach--remain to be fully addressed. Despite this, preclinical studies on cardiomyocyte transplantation in animals and the first clinical trials with adult stem cells have recently been published with mixed results. 相似文献
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Cardiovascular development: towards biomedical applicability 总被引:3,自引:0,他引:3
Filipczyk AA Passier R Rochat A Mummery CL 《Cellular and molecular life sciences : CMLS》2007,64(6):704-718
Investigating the signalling pathways that regulate heart development is essential if stem cells are to become an effective source of cardiomyocytes that can be used for studying cardiac physiology and pharmacology and eventually developing cell-based therapies for heart repair. Here, we briefly describe current understanding of heart development in vertebrates and review the signalling pathways thought to be involved in cardiomyogenesis in multiple species. We discuss how this might be applied to stem cells currently thought to have cardiomyogenic potential by considering the factors relevant for each differentiation step from the undifferentiated cell to nascent mesoderm, cardiac progenitors and finally a fully determined cardiomyocyte. We focus particularly on how this is being applied to human embryonic stem cells and provide recent examples from both our own work and that of others. 相似文献
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