Researchers from the New York Stem Cell Foundation have used somatic cell nuclear transfer (SCNT) to create patient-specific stem cells, which were subsequently differentiated into insulin-producing pancreatic beta cells, from an adult diabetic woman. Study lead Dieter Egli said the findings mark "the first report describing diploid patient-specific stem cell lines after somatic cell nuclear transfer."

Together with a report that appeared last week, he added, it is also "the first report on the derivation of diploid pluripotent stem cell lines from cells of an adult and from a human being after birth in general."

Egli and his team published their results in the April 28, 2014, advance online edition of Nature. In a paper published earlier this month in Cell Stem Cell, researchers had used SCNT to generate stem cell lines from two healthy adult males, one of them elderly.

Medically, in the long run, the advance may allow the generation of patient-specific stem cells for cell replacement therapies.

Whether those replacement therapies come to pass, and if so, whether the procedure used to generate such replacement cells will ultimately be based on SCNT, is an open question.

For now the greatest significance of the results is that they illustrate the tenacity of researchers in continuing to work with embryonic stem cells – a sign of how strong the scientific promise of embryonic stem cells is and remains, despite the ethical and legal morass that surrounds them.

With the creation of induced pluripotent stem (iPS) cells in 2007, many policymakers assumed – or hoped – that morass would go away as embryonic stem cells would be replaced by equally pluripotent and ethically uncomplicated iPS cells.

But a strong faction within the scientific community itself – including both researchers working on ES and iPS cells – understood the importance of comparing the medical merits of both cell types.

Egli and his team had previously created stem cells via SCNT. But to get the procedure to work, they had to keep the DNA of the egg cell used in the procedure, making them therapeutically useless. (See BioWorld Today, Oct. 5, 2011.)

In the work now described in Nature, the team tweaked the protocol to get rid of that extra chromosome, as well to make the procedure more efficient in other ways.

Egli said that "a key step" was to prevent premature activation, but then applying strong stimulus for activation that pushes the egg efficiently out of meiotic arrest, which is normally done by fusion with the sperm. Another was to use HDAC inhibitors to remodel the chromatin of the patient DNA into a stem cell-like state.

Egli said that with those tweaks, the efficiency is such that it should ultimately be possible to reliably derive a stem cell line per egg donation.

The generation of SCNT-derived stem cells will allow a scientific understanding of which cell types, from a purely scientific point of view, would be preferable for use in cell replacement therapies.

Egli said his team is "very keen" to directly compare iPS and SCNT stem cells derived from the same patients. "We don't yet know from what type of a cell a cure or better treatments are going to come, and so we feel it is essential to pursue all appropriate avenues in this quest. . . . We still don't know as of today whether there are differences between the two cell types that may make one cell type vs. the other more suitable for transplantation."

But not surprisingly, he was optimistic about the relative merits of SCNT.

"I think as the field currently stands, if you had a choice . . . between the two cells, you would choose the nuclear transfer cells, because there are simply more uncertainties about the iPS cells," he said.

Not that certainties abound with the SCNT-derived cells. The research area receives no federal support, there is vocal conservative opposition to creating what some people consider a person only to destroy it, and with millions of patients suffering from the types of disorders – type I diabetes, Parkinson's disease – that could benefit from cell replacement, the method has the potential to exceed the supply of eggs that could be procured from donors. For now, even getting enough eggs for research purposes can be a scramble. The team moved its work from Massachusetts to New York in order to be able to compensate its egg donors, which received $8,000 each, a payment that is in line with what egg donors are paid in fertility clinics.

But Egli pointed out that the very use of donated eggs in fertility clinics is also a current clinical routine in a way that the use of iPS cells is not. Whether it is the clarity of the visionary or the blindness of the true believer, his take on the future of SCNT was that eggs are transplanted routinely, and so one regulatory framework to use them does exist. "We may be much closer to translating this," he declared, "than we may think."