Yesterday, researchers published a paper in the journal Cell announcing that they had successfully produced the first human-pig chimera—an embryo that contains cells from two genetically distinct species. The controversial study is the first step in growing human organs in non-human host animals for transplantation.
According to Hannah Devlin at The Guardian, the research was led by a team at the Salk Institute for Biological Studies in La Jolla, California. The scientists transformed cells from an adult human into stem cells, then injected those into early-stage pig embryos. These embryos were then implanted into female pigs where they were allowed to develop for three to four weeks, what amounts to the first trimester of a pig pregnancy.
Erin Blakemore at National Geographic reports that 186 of the embryos developed into later-stage chimera embryos. In each later-stage pig embryo, about 1 in every 100,000 cells was human-derived.
Getting to even this earliest stage has been a long journey, reports Blakemore. Before moving on to human-pig chimeras, Belmonte and his colleagues first worked on mouse-rat chimeras. By using CRISPR/Cas9 gene editing, the researchers were able to remove the genes for certain organ formation from mouse blastocysts (a blastocyst is the cellular stage before the embryo).
They then injected rat stem cells into the blastocysts. They found that the stem cells filled the gaps and developed the missing organs, including a heart, pancreas and eye.
The researchers then attempted a similar procedure injecting rat stem cells into pig blastocysts. But that combination didn’t work, mainly because the development timeline for the two animals is so far apart. The researchers then moved on to pigs and humans which have different gestation times (a pig's pregnancy lasts about 112 days), but more similar organs.
It then took a lot of trial and error to find stem cells that developed along a similar timeline. “We tried three different types of human cells, essentially representing three different times,” Jun Wu, the first author on the paper tells Blakemore.
The work could eventually provide life-saving organs for those waiting on donor lists, but critics of the research believe that mixing humans and animals in any way crosses a line. In the United States, the National Institutes of Health has banned federal funding for human chimera research, though last August it signaled it might relax that ban for carefully monitored experiments.
Daniel Garry, a cardiologist who is leading a research project on chimeras at the University of Minnesota, tells Devlin he thinks the Salk experiment was performed ethically and responsibly. “This is a significant advance that raises opportunities and ethical questions as well,” he says, pointing out that many people's fears of half-man, half-beast chimeras are not really in the range of possibility in this study.
Things will get more complicated as the research progresses, however. “At this point, we wanted to know whether human cells can contribute at all to address the 'yes or no' question,” Belmonte says in a press release. “Now that we know the answer is yes, our next challenge is to improve efficiency and guide the human cells into forming a particular organ in pigs.”