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Scientists Awed, Skeptical Over Mature Cell Reprogramming



Concerns are continuing to arise over the news that researchers from Japan recently discovered a revolutionary phenomenon in which mature differentiated cells can be reprogrammed to become pluripotent embryonic cells, which can then differentiate into one of many cell types.

Haruko Obokata, a stem-cell biologist at the RIKEN Center for Developmental Biology in Kobe, is lead author on the paper “Stimilus-triggered fate conversion of somatic cells into pluripotency” published in the prestigious journal Nature in January. The cell-switch mechanism, dubbed stimulus-triggered acquisition of pluripotency (STAP), was achieved by applying stress to a mature mouse cell.

According to Dennis Clegg, founder and co-director of the UCSB Center for Stem Cell Biology and Engineering, a pluripotent cell can be reprogrammed into a cell with a different function, whereas a differentiated cell has its fate — perhaps as a brain or muscle cell — determined.

“Pluripotent means that you can make almost anything,” Clegg said.

Obokata and fellow researchers employed STAP to stimulate a mouse’s differentiated spleen cell into a pluripotent cell by exposing the cells to an acid bath.

But now the reproducibility of Obokata’s findings are being questioned by the scientific community.

Clegg said that there is high interest in Obokata’s findings, but many stem cell researchers are approaching the study with a grain of salt.

“People are questioning some of the results. It is not obvious fraud so far. The question is: Can other people reproduce it in other labs?” Clegg said. “So far we are getting started on that. We do not know if we can reproduce it yet. It will take some time. Right now my Post-Doc is testing that.”

It is generally accepted that there exists only a few methods to change a cell’s fate, such as nuclear transfer or the introduction of transcription factors. Transcription factors are proteins that bind to specific sequences of genes to control gene expression.

The external trigger via acid bath stirred excitement in the research community because it did not directly manipulate a cell’s DNA. By placing stress on the already differentiated cell, the low pH environment induced the cell to reprogram itself without the introduction of transcription factors.

Clegg said that STAP makes the production of pluripotent cells facile.

“It represents an easier way to reprogram cells. We already know how to reprogram [differentiated] cells; it is straightforward and very reproducible now,” Clegg said.

Activating a differentiated cell to transform into a pluripotent cell is only one hurdle. Transforming a pluripotent cell that originally came from a skin cell into a neuron, for example, is a different challenge.

According to Clegg, Obokata’s use of mouse cells poses the usual limits of animal studies in the community.

“In terms of curing a bunch of diseases it is not quite there yet,” Clegg said. “I know a number of labs that are looking at that and we are interested to see if it would work in human cells.”

While scientists around the world attempt to duplicate these perhaps unbelievable results, the RIKEN Center for Developmental Biology in Kobe said that it is looking into allegations of issues regarding Obokata’s results.

 

Researchers subjected differentiated mouse cells to an acid bath to induce an embryonic state.

Researchers subjected differentiated mouse cells to an acid bath to induce an embryonic state.

Photo Courtesy of Haruko Obokata

A version of this story appeared on page 6 of Wednesday, March 5, 2014′s print edition of the Daily Nexus.

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