Scientists have successfully created pig embryos that contain a small fraction of human cells, according to a study published Thursday in Cell.

The study, led by researchers at the Salk Institute in California, represents a significant step toward human-animal hybrids that could one day grow whole new human organs for transplant. Right now, the pig hybrids only contain about one human cell to 100,000 pig cells and were very tricky to make. And due to ethical guidelines, the researchers only let them develop for about a month. But researchers are optimistic that they’ll be able to tackle the technical—and ethical—challenges moving forward.

They certainly have a lot of hints that they’ll be successful.

To show that cells from two different species can share one body in harmony, the researchers also created mice with rat organs. They used a snazzy new genetic engineering tool called CRISPR/Cas9 to break a few genes in mouse embryos that dashed their ability to develop several organs properly, including the pancreas, heart, and eye. Next, the researchers injected the embryos with rat stem cells, then transferred the embryos into a mouse’s uterus to develop. The embryos developed into healthy animals with hybrid mouse-rat organs, the researchers found. In fact, the rat cells even developed into gall bladders in the mice, despite the fact that rats don’t have these organs. The animals all lived normal mouse lives of up to two years.

And another group led by researchers at Stanford reported this week that it too had created a mashup: a rat growing a mouse pancreas. The researchers used a similar technique as the Salk researchers, but they took the extra step to transfer pancreas cells from their hybrid rats to diabetic mice. The transplant restored insulin production and reversed the disease in the sick mice. That study, which provides a proof-of-principle for inter-species organ transplants, appeared Wednesday in Nature.

Salk Institute

Salk Institute

Salk Institute

Salk Institute

Salk Institute

Tomoyuki Yamaguchi

Salk Institute

Salk Institute, JUAN CARLOS IZPISUA BELMONTE

Salk Institute

Salk Institute

Hybrid hurdles

The last leap is getting cells from distantly related species to live side by side. The Salk team turned to cows, pigs, and humans. For the human cells, the researchers used induced pluripotent stem cells (iPSCs), which are normal adult cells that have been chemically coaxed into reverting to a stem cell state.

A sticking point in the past has been getting iPSCs to take root in an embryo, which requires their development to be in sync with that of the embryo’s cells. So the researchers tried priming the iPSCs for organ development. They injected them into embryos at various stages—not primed, moderately primed, and fully primed. They found the moderately primed ones did the best at surviving and integrating into the embryos.

The researchers also genetically engineered the cells to produce a green fluorescent protein so that they could easily spot them in animal embryos.

The researchers tested out a cow-human hybrid, but it was fussy and expensive to work with, so they focused in on the pig-human hybrid. The scientists made pig embryos in petri dishes and then injected them with human iPSCs; a total of 2,075 injected embryos were implanted into 41 sows. Only 18 of the sows got pregnant and 186 embryos survived. Of those, only 67 appeared to contain human cells, based on the green glow, and only 17 looked normal after 21 to 28 days of development. The rest looked underdeveloped, suggesting that the human cells disrupted normal pig development.

So it worked, but not well. The researchers are now moving forward with experiments using pig embryos that have genetic modifications that might make them more hospitable to the human cells.

In the meantime, ethicists are urging researchers to think carefully about their experiments and the implications for animal rights and the lives of human-like creations, particularly ones with human-like brains and reproductive organs. Currently, the US government has a ban on using federal funding to support research into human chimeras. (The new study was conducted mostly with private money.) However, last August, the National Institutes of Health announced that it was rethinking the ban.

Cell, 2017. DOI: 10.1016/j.cell.2016.12.036 (About DOIs).

Nature, 2017. DOI: 10.1038/nature21070