Mouse heart beats again thanks to human stem cells

A newly beating heart is part-mouse, part-human. For the first time, a mouse heart has been made to pulse again by stripping it of its own cells and rebuilding it with human ones (see video above).

To create the hybrid heart, Lei Yang at the University of Pittsburgh and colleagues took the heart from a mouse and, in a process that lasted 10 hours, removed all its cells. The remaining protein scaffold was then repopulated with human heart precursor cells stem cells that had differentiated into the three types of cell required for a heart. After a few weeks, the organ started to beat again. "Our engineered hearts contain about 70 per cent human heart precursor cells, which provide enough mechanical force for contraction," says Yang.

The precursor cells were derived from induced pluripotent stem cells generated from human skin cells, and were then turned into cardiac precursor cells. A previous study used human embryonic cells to achieve similar results, but the success rate in converting them to beating heart cells was very low.

Although the designer hearts do beat rhythmically, they aren't strong enough to pump blood effectively and the team found that the heart's rhythm differed from a normal mouse's heart. Yang thinks this is because the added cells were not as mature as adult heart cells or properly synchronised. "We did not rebuild the whole cardiac conduction system, which could control the rhythmic beatings of a heart," he says. The team's next step will be to improve the mechanical and electrical synchronisation of the heartbeat.

The study builds on previous work by Yang and colleagues where human heart precursor cells, derived from embryonic stem cells, successfully differentiated into different heart cells when injected into a mouse heart. In another recent study, a rat's heart was bioengineered by seeding a scaffold with another rat's stem cells.

Yang's long-term goal is to create human hearts that can be used for transplants, for drug testing and to better understand how a heart develops. "Using our method, we could generate both muscle and vascular-like structures in the engineered heart constructs," says Yang. "We hope to make a piece of human heart tissue soon but our dream is to regenerate a human heart organ."

The main challenge is to scale up the system to work with human heart scaffolds. There, the biggest problem will be the sheer number of cells needed to reseed a human heart.

Journal reference: Nature Communications, DOI: 10.1038/ncomms3307

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Mouse heart beats again thanks to human stem cells