AUG 08, 2016 11:04 AM PDT

Changes to Human-Animal Stem Cell Research Guidelines Proposed

WRITTEN BY: Carmen Leitch
In a blog post by Carrie Wolinetz, the Associate Director for Science Policy, the National Institutes of Health (NIH) announced that it is considering lifting part of its moratorium on stem cell research that combines human and animal cells.
Human Embryonic Stem Cells / Credit: Nissim Benvenisty
In her post, Wolinetz reminds us that researchers have turned to animal models to study human diseases for decades, including modeling human tumors by growing them in animals, and validating the efficacy of stem cells by inserting them into rodents. There is concern however, when those cells are inserted into developing animals such that an adult animal develops human parts – especially human brain parts.

Paul Knoepfler, a researcher that works on stem cells at the University of California, Davis told the New York Times that “there’s no clear dividing line because we lack an understanding of at what point humanization of an animal brain could lead to more humanlike thought or consciousness,” he said.

New advances in gene editing technologies led the NIH to halt research that was moving in a direction that caused some ethical concern. As part of their mission to oversee research, they have to anticipate where research is headed. After prohibiting the introduction of human pluripotent stem cells into nonhuman primate blastocysts and banning the breeding of animals that have had their germ line genomes altered by pluripotent human cells in 2009, the NIH felt it was time to revisit those restrictions and how they might apply to other animal models.

An expansion of those guidelines last September halted funding to projects that aimed to introduce human pluripotent cells into animals prior to gastrulation – an early stage of embryonic development when the embryo goes from two to three cellular layers.

Last November, researchers convened at the NIH to discuss the state of research into chimeras – an organism that is made up of cells that came from different zygotic sources. The NIH now proposes two changes in their policies, and is seeking public comment on these proposals.

One change will expand the restriction of human stem cell insertion into pre-blastocyst non-human primate embryos, and expand the breeding restriction to include animals in which any human cells (not just human embryonic or induced pluripotent stem cells) could contribute to the germ line. If you would like to know more about these developmental terms, check out the video below the article.

The other change seeks to allow researchers to use human cells in non-human mammals after the gastrulation stage, if the research could make a substantial contribution to either the animal brain or a functional modification to an animal brain.
Image from Nature / Source: Adapted from M. D. Li et al. Regen. Med. 9, 27-39 (2016)
Dr. George Q. Daley, who is both a Harvard professor and the director of the stem cell transplantation program at Boston Children’s Hospital, has given The New York Times a little insight into this work.
He explains that researchers wanted to know if they had captured new kinds of stem cells capable of turning into any type of tissue or organ. Finding out means putting those cells into an embryo to see how they develop – do they form a placenta and can they create any cell type in the adult animal?

In other experiments, scientists want to assess human stem cells that developed into specific tissue types. One team of investigators found that when rat stem cells are put into a mouse embryo lacking the genes for making a pancreas, a mouse with a rat pancreas is created.

So could a pig grow a human organ for transplant? “It’s science fiction today, but there has been enough progress in rat to mouse and even in pigs that it is at least theoretically possible,” Dr. Daley explained.
Another team, aiming to reveal more about human psychiatric dysfunction, studied the use of human stem cells in mice embryos. In a teleconference, Wolinetz said that she expects “some on-the-job learning” about chimeras in which human cells are a part of the brain.

“There is a lot we don’t understand about the brain,” she said, “which is one reason the possibility of these animal models is really exciting.”

It may take time for the public to come to terms with this research, as we grapple with the ethics and philosophical questions that arise when genes of two species are mixed.

Sources: NIH, The New York Times, Nature
About the Author
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