Producing a Beating Mouse Heart Through Recellularization

Decellularization is the process of taking a complex organ or other tissue structure and stripping the cells from it, leaving behind the supporting extracellular matrix. The matrix can then be repopulated by new cells of the appropriate types in order to recreate a functional organ. This is in any case is the end goal of this ongoing line of research: decellularization has been used in recent years to produce tracheas and heart valves for transplantation, populating the tissue with the recipient's own cells so as to eliminate the possibility of rejection.

A trachea is a comparatively simple structure, however. Just as for tissue engineering of organs from scratch, there are hurdles to be overcome in making decellularization a practical option for organs and tissues that are more functional than structural: lungs, livers, hearts, for example While it is certainly the case that decellarization is lot closer to practical application for heart engineering than building a heart from a patient's own stem cells using bioprinting technologies, or other from-scratch strategies, there is work yet to be done. See this latest research, for example, in which a beating mouse heart is produced, but not one that performs well enough to be a transplant candidate:

Decellularized Mouse Heart Beats Again After Regenerating With Human Heart Precursor Cells

For the project, the research team first "decellularized," or removed all the cells, from a mouse heart, a process that takes about 10 hours using a variety of agents. Then, they repopulated the remaining heart framework, or scaffold, with [human] multipotential cardiovascular progenitor (MCP) cells. These replacement cells were produced by reverse engineering fibroblast cells from a small skin biopsy to make induced pluripotent stem cells and then treating the iPS cells with special growth factors to further induce differentiation.

"This process makes MCPs, which are precursor cells that can further differentiate into three kinds of cells the heart uses, including cardiomyocytes, endothelial cells and smooth muscle cell. Nobody has tried using these MCPs for heart regeneration before. It turns out that the heart's extracellular matrix - the material that is the substrate of heart scaffold - can send signals to guide the MCPs into becoming the specialized cells that are needed for proper heart function."

After a few weeks, the mouse heart had not only been rebuilt with human cells, it also began contracting again, at the rate of 40 to 50 beats per minute, the researchers found. More work must be done to make the heart contract strongly enough to be able to pump blood effectively, and to rebuild the heart's electrical conduction system correctly so that the heart rate speeds up and slows down appropriately.

"One of our next goals is to see if it's feasible to make a patch of human heart muscle. We could use patches to replace a region damaged by a heart attack. That might be easier to achieve because it won't require as many cells as a whole human-sized organ would."

Other research teams have prototyped heart patches via decellularization in recent years. It seems to be a popular choice of stepping-stone product for use in medicine, a waypoint on the road to rebuilding hearts completely. There is more competition here from researchers who aim to grow tissues from scratch, however, as they too have demonstrated the ability to create prototype heart patches. So while I don't think that there's any great doubt that decellularization will reach the clinic for whole organs in advance of tissue engineered solutions, it's a different story for smaller and less complex tissue masses.

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