Major progress toward cell reprogramming

Two Harvard Stem Cell Institute (HSCI) researchers and scientists at Whitehead Institute and Japan’s Kyoto University have independently taken major steps toward discovering ways to reprogram cells in order to direct their development – a key goal in developmental biology and regenerative medicine.

Additionally, the group led by Kevin Eggan, an HSCI principal faculty member – whose study is featured on the cover of the latest issue of the journal Nature – has disproved a long-held view of developmental biologists by demonstrating in mice that it is possible to use previously fertilized ova to produce disease-specific stem cell lines using somatic cell nuclear transfer (SCNT) – commonly referred to as therapeutic cloning.

For almost three decades it has been a given in developmental biology that only unfertilized ova could be used to do SCNT, and difficulty in obtaining fresh ova has brought that work to a standstill. “Now we’re able to do an experiment a week, where we hadn’t been able to do a single experiment for a year,” Eggan said.

In another approach to the problem of reprogramming cells, groups led by Kyoto’s Shinya Yamanaka, Rudolph Jaenisch of the Whitehead, and Konrad Hochedlinger of HSCI and Massachusetts General Hospital’s Center for Regenerative Medicine report the use of four genes to transform an adult cell into a cell with the properties of an embryonic stem cell – replicating and expanding upon seminal work published last year by Yamanaka. The Jaenisch and Yamanaka papers are being published in Nature; Hochedlinger’s is in the inaugural issue of Cell Stem Cell.

HSCI co-director Doug Melton hailed the work, saying, “These new studies, done with mouse cells, point the way to experiments that can be tried with human cells and represent some of the most exciting work in stem cell biology and genetic reprogramming.”

Commenting on Eggan and Hochedlinger’s work, Melton, the Thomas Dudley Cabot Professor of the Natural Sciences in Harvard’s Faculty of Arts and Sciences, said, “These exciting papers both address an important issue in developmental biology, namely, how can we change – or reprogram – a cell, turning it ‘back’ to a more embryonic state with a greater potential? The promise of both approaches is the possibility that we will be able to create embryonic stem cells from patients, and use those cells to study the root causes of degenerative diseases.”

While all four reports are expected to cause enormous excitement in the stem cell and research communities, to a person the researchers are cautioning that thus far their studies have been conducted using mouse cells and mice, and there is no way to know whether they will translate precisely – if at all – to humans.

Eggan estimates that there is a substantial number of fertilized ova, or single-cell zygotes, in storage in fertility clinics, and has received all necessary approvals from Harvard Institutional Review Boards to begin experiments using them. While he has yet to have a single ova donation, Eggan said there are already couples donating frozen zygotes for research.