Scientists isolate new human pluripotent stem cells

October 31, 2013
New stem cells go back further
This image shows how human naive iPS derived cells (yellow/green cells) integrate in different tissues of developing host mouse embryo (red cells). Credit: Weizmann Institute of Science

One of the obstacles to employing human embryonic stem cells for medical use lies in their very promise: They are born to rapidly differentiate into other cell types. Until now, scientists have not been able to efficiently keep embryonic stem cells in their pristine stem state. The alternative that has been proposed to embryonic stem cells – reprogrammed adult cells called induced pluripotent stem cells (iPS cells) – have similar limitations. Though these can differentiate into many different cell types, they retain signs of "priming," – commitment to specific cell lineages.

A team at the Weizmann Institute of Science has now taken a large step toward removing that obstacle: They have created iPS cells that are completely "reset" to the earliest possible state and maintained them in that state. Among other things, this research may, in the future, pave the way toward the ability to grow transplant organs to order.

Since they were first created in 2006, iPS cells have been touted as an ethical and practical substitute for embryonic . They are made by inserting four genes into the genomes of such as . This turns back the developmental clock almost all the way – but not completely – to an embryonic-stem-cell-like state. Dr. Jacob Hanna of the Institute's Molecular Genetics Department and his team, including research students Ohad Gafni and Leehee Weinberger and researchers in the Israel National Center for Personalized Medicine, realized that inserting genes to reset the stem cells was not enough. One also has to put the cells' drive to differentiate on hold.

One hint that this might be possible was the fact that the mouse embryonic stem cells used in many lab experiments are easily preserved in their "naive," unprimed state, and they don't present some of the other problems that human ones do. Hanna and his group realized that if they could understand how the mouse embryonic stem cells manage to refrain from differentiating in the lab, they could apply it to the human versions. Through lab experiments and genetic analysis, they worked out a "treatment" for the iPS cells in the lab dish to damp down the genetic pathway for differentiation.

This video is not supported by your browser at this time.
Human naive iPS-derived cells (yellow/green) are shown integrating into different tissues of a developing host mouse embryo (red cells). Credit: Weizmann Institute of Science

Next, they injected the treated iPS cells into mouse blastocysts – early-stage embryos containing only a few cells. If the team's iPS cells were truly na?ve, as well as viable, they would grow together with the . Adding a fluorescent marker to the iPS cells enabled them to trace what happened to those stem cells in the developing embryo. Fluorescent imaging after ten days (they were not grown to term) indeed revealed that the embryos contained both mouse and human tissues.

This video is not supported by your browser at this time.
Human naive iPS-derived cells (yellow/green) are shown integrating into different tissues of a developing host mouse embryo (red cells). Credit: Weizmann Institute of Science

Hanna: "These cells correspond to the earliest stages of human that have been isolated. We managed to freeze what is essentially a very fleeting situation and to produce a new, na?ve, pluripotent state in stem ." These findings may have many uses in biomedical research, specifically in gene therapy research, as well as genetic engineering. Hanna and his team plan to continue investigating the "humanized" mouse embryos, in which they hope to find ways of directing the development of human tissue into functional organs.

Explore further: Test to improve stem cell safety

Related Stories

Test to improve stem cell safety

June 4, 2013

CSIRO scientists have developed a test to identify unsafe stem cells. It is the first safety test specifically for human induced pluripotent stem cells (iPS) – as published today in the international journal Stem Cells.

Stem cell reprogramming made easier

September 18, 2013

Weizmann Institute scientists show that removing one protein from adult cells enables them to efficiently turn back the clock to a stem-cell-like state.

Recommended for you

Scientists overcome key CRISPR-Cas9 genome editing hurdle

December 1, 2015

Researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have engineered changes to the revolutionary CRISPR-Cas9 genome editing system that significantly cut down on "off-target" ...

Study finds 'rudimentary' empathy in macaques

December 1, 2015

(—A pair of researchers with Centre National de la Recherche Scientifique and Université Lyon, in France has conducted a study that has shown that macaques have at least some degree of empathy towards their fellow ...

Which came first—the sponge or the comb jelly?

December 1, 2015

Bristol study reaffirms classical view of early animal evolution. Whether sponges or comb jellies (also known as sea gooseberries) represent the oldest extant animal phylum is of crucial importance to our understanding of ...

Trap-jaw ants exhibit previously unseen jumping behavior

December 1, 2015

A species of trap-jaw ant has been found to exhibit a previously unseen jumping behavior, using its legs rather than its powerful jaws. The discovery makes this species, Odontomachus rixosus, the only species of ant that ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.