Cloning With Caffeine Produces Patient-Matched Stem Cells

Scientists have created embryonic stem cells that are a near identical genetic match to patients, an advance that could enable transplants and treatments based on an individual’s own tissues.

The researchers, at Oregon Health & Science University in Portland, made embryonic stem cells through a procedure known as somatic cell nuclear transfer, which involved taking DNA from skin cells and inserting it into donated human egg cells. The resulting stem cells thrived and could be turned into a variety of cell and tissue types, including heart cells, according to the study published in the journal Cell.

The advance was enabled by a surprising ingredient, according to the report: caffeine gave the cells the boost they needed to remodel the donor DNA into embryonic cells.

“It is a significant step,” said Dieter Egli, senior research fellow at the New York Stem Cell Foundation Research Institute. If embryonic stem cells “can be made from adults like us, that would mean we could make replacements for any type of cells we would need.”

The study improves on results from two years ago at the New York Stem Cell Foundation and Columbia University, where researchers, including Egli, created the first embryonic stem cells using human eggs. While the cells from that research had an extra set of chromosomes that made them useless for therapeutic purposes, the new study describes a different method that tackles the problem.

Caffeine Ingredient

Using a technique similar to that used to create Dolly the cloned sheep in 1996, scientists removed the nucleus from a donated human egg cell and replaced it with the nucleus of a skin cell. By adapting procedures from the previous work, they grew the cells into colonies of embryonic stem cells that differentiated into a variety of cells and tissues, said Shoukhrat Mitalipov, senior author of the study and professor at Oregon Health & Science University.

A limitation in the prior study involved the difficulty in removing the egg cell’s nucleus. In that study, researchers inserted a second nucleus into the cell, defeating the purpose of creating patient-specific cells, Mitalipov said.

Caffeine turned out to be an important step in solving the problem this time around, according to Egli, who wasn’t involved in the study. “They found that if you add caffeine, you can correct the defect introduced by removing the oocyte genome,” he said in a telephone interview.

Caffeine has been used in animal cloning, including by Keith Campbell, who cloned Dolly the sheep, Egli said. “It seems to enhance programming efficiency.”

Next Step

Mitalipov said a next step is to compare these embryonic stem cells with induced pluripotent stem cells, adult cells that have been coaxed back to an immature state. Work leading to so-called iPS cells, by Shinya Yamanaka and John B. Gurdon, won the Nobel Prize in Physiology or Medicine in 2012.

“We produced a new class of stem cells,” Mitalipov said. “Now we’d like to compare these SCNT-derived stem cells to iPS cells and see which one produces the best results.”

The hope is that one day, patients with diseases from Parkinson’s to diabetes could benefit from regenerative medicine using their own genetic material.

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