Reinnervation and Cardiac Regeneration (p 990)
White et al discover that reinnervation is essential for regenerating the neonatal heart.
For a limited period during development, the heart of a newborn mouse can almost entirely regenerate after injury. This ability is lost when the animal matures, but understanding how the heart of a newborn mouse regenerates could enable researchers to reactivate the process in patients who have suffered myocardial damage. Among the many examples of organ or limb regeneration in vertebrates and invertebrates one common feature seems to be concomitant reinnervation of the regenerating tissue. To examine whether this is also the case in neonatal heart regeneration, White and colleagues examined peripheral nerve arrangements in the hearts of newborn mice before and after resection of the apex. They found that two weeks after resection there was hyper-innervation at the injury border. And by three weeks the apex had entirely regrown and re-innervated displaying a normal pattern of branching nerves. To identify the role of this re-innervation, the team prevented nerve growth 48 hours after heart resections by chemical sympathectomy. They discovered that, unlike control animals, sympathectomized mice showed no apical regeneration at all, but only scarring, thus identifying that reinnervation is essential for cardiac regeneration in newborn mice.
Matrigel Mattress Generates Contracting hiPSC-CM (p 995)
Feaster et al have figured out an easy way to get human iPSC-derived cardiomyocytes into better shape for contraction.
Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are an invaluable resource for studying the biology of human heart diseases as well as for drug discovery and toxicity screening. Therefore, it is essential that hiPSC-derived cardiomyocytes closely resemble adult cardiac cells. Although the electrophysiological and calcium-handling properties of hiPSC-cells are similar to adult cardiomyocytes, their contractile properties are not well developed. The problem in large part is due to the geometry of the cells; instead of being long and thin with aligned sarcomeres, like native cardiomyocytes, the hiPSC are more variable and they have no dominant axis of sarcomere arrangement. Now, Feaster and colleagues have developed a simple method to encourage hiPSC-cardiomyocytes to elongate and, as a result, to contract more robustly. The method involves seeding the hiPSC-cardiomyocyte on millimeter scale strips of matrigel, which they call matrigel mattresses. These mattresses appear to guide cell growth, and in less than a week, the cells exhibit rod-like morphologies, aligned sarcomeres and display contractile abilities similar to those of primary adult cardiomyocytes.
Bone-Derived Stem Cells Augment Cardiac Repair (p 1024)
Mohsin et al compare cortical bone stem cells to other stem cells used for heart repair.
The idea of using stem cells to repair injured hearts has captured the attention of both scientists as well as the general public. However, even though initial laboratory investigations showed promise, clinical trials to date have yielded modest improvements at best. This may be due to several reasons, including poor engraftment and insufficient proliferation, survival, and differentiation of stem cells. It is also likely that the relevant stem cell or appropriate mix of stem cells optimal for cell therapy has not yet been discovered. The search for new candidate cell types is thus an ongoing quest. Stem cells derived from cortical bone have been shown previously to improve cardiac function in a mouse model of myocardial infarction, but how these cells compare with other cell types used in clinical trials is unknown. Mohsin and colleagues performed a series of in vitro comparisons between cortical bone stem cells (CBSCs), mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs) and found that CBSCs proliferated faster and survived apoptotic insult better than the other two types of stem cells. The CBSCs were also much better at protecting co-cultured cardiomyocytes from apoptotic insult. Finally, upon differentiation, CBSCs exhibited higher levels of markers of cardiac lineage commitment than either MSCs or CDCs. These results suggest that CBSCs deserve further investigation as potential therapeutic candidates in future cell therapy trials.
- © 2015 American Heart Association, Inc.