Researchers Report Advances in Cell Conversion Technique

By NICHOLAS WADE  

Biologists at Harvard have converted cells from a mouse’s pancreas into the insulin-producing cells that are destroyed in diabetes, suggesting that the natural barriers between the body’s cell types may not be as immutable as supposed.

This and other recent experiments raise the possibility that a patient’s healthy cells might be transformed into the type lost to a disease far more simply and cheaply than in the cumbersome proposals involving stem cells.

The new field depends on capturing master proteins called transcription factors that control which sets of genes are active in a cell and thus what properties the cell will possess. Each type of cell is thought to have a special set of transcription factors.

Last year a Japanese biologist, Shinya Yamanaka, showed that by inserting four transcription factors into an adult cell he could return it to its embryonic state.

In a variation of this technique, a team led by Qiao Zhou and Douglas A. Melton at Harvard has now identified three transcription factors active in the insulin-producing beta cells of the pancreas.

They hitched the genes for these three factors onto a virus that infects another type of pancreatic cell, known as an exocrine cell. In mice made diabetic by a drug that kills beta cells, the transformed exocrine cells generated insulin, allowing the mice to enjoy “a significant and long-lasting improvement” in their diabetic state, the researchers are reporting Thursday in the journal Nature.

Many steps remain before the technique could be considered for human use.

Besides producing insulin, the transformed exocrine cells looked like beta cells and ceased making proteins typical of exocrine cells. But they did not organize themselves into the pancreatic structures known as islets where beta cells usually cluster. The researchers claim only to have made “cells that closely resemble beta cells.”

Even so, Robert Blelloch, a cell biologist at the University of California, San Francisco, said, the Harvard experiment was “a very nice story — it’s pretty impressive that you can make such a switch just by adding three factors to a quite different cell type.”

Last month Patrick Seale and Bruce Spiegelman of the Dana-Farber Cancer Institute in Boston showed how with a single transcription factor they could make white fat cells generate brown fat cells, a very different type of cell.

The Harvard work “is not occurring in a vacuum, but it’s a very important piece of work,” Dr. Blelloch said.

BIO 2008: Comparing stem cells Joint NSW/Victorian project to compare three types of stem cells

Scientists from Sydney IVF and the Australian Stem Cell Centre (ASCC) in Melbourne have launched a project to characterise and compare induced pluripotent stem cells, human embryonic stem cells and stem cells derived from somatic cell nuclear transfer.

The aim of the project is to develop a routine, repeatable way of making patient-specific stem cells within current legislative guidelines.

The NSW Minister for Science and Medical Research, Verity Firth, and the Victorian Minister for Innovation, Gavin Jennings, made the announcement today at the BIO 2008 convention in San Diego.

Each government has pledged $550,000 to the project. NSW will fund Sydney IVF to undertake the SCNT work, while Victoria has funded the ASCC to perform the characterisation and comparison of the stem cells.

The ASCC recently announced it was the first international group to import iPS cells, licensing them from Professor James Thomson at the University of Wisconsin. Thomson described the development of iPS cells in one of two ground-breaking papers in November last year.

"The combination of the international quality talent and significant resources of these two collaborative partners gives this project the potential to provide world-first advancements in these new biological frontiers," Firth said.

Firth, on her first trip to BIO since becoming a minister 18 months ago, said the project was a collaboration not only between scientists but between governments.

"We have real excellence in stem cell research both in NSW and Victoria," she said. "One thing you learn at BIO is that we are Australia here - it's a bit silly for the states to compete."

ASCC scores iPS cellsAustralian scientists to study iPS cells from Thomson lab.

Scientists from the Australian Stem Cell Centre (ASCC) will be the first in Australia to gain access to human induced pluripotent stem (iPS) cells from Professor James Thomson of the University of Wisconsin.

The iPS cells have been imported under an agreement with Thomson, who has developed the human iPS cell lines and was, at the same time as Professor Shinya Yamanaka from the University of Kyoto, the first to describe human iPS cells in November 2007.

Thomson was also the first scientist to identify and describe human embryonic stem cells in the scientific press in 1998 and has been a leader in the field of embryonic stem cell research since.

Both scientists use retroviruses to insert genes into human skin cells to reprogram them. Each uses slightly different genes in the procedure.

The human iPS cells arrived at the ASCC's Melbourne laboratories in late May. Drs Andrew Laslett and Naoki Nakayama, both senior scientists in the human embryonic stem cell laboratory, will be the first at the ASCC to work with them.

"We plan to comprehensively compare the iPS cell lines to existing human embryonic stem cell lines using the first class scientific infrastructure and innovative characterisation and differentiation strategies in place at the Australian Stem Cell Centre," Laslett said.

"These experiments will give us a greater understanding of the relative utility, advantages and potential barriers to the clinical use of iPS cells as compared directly to human embryonic stem cells."

Scientists Reprogram Fully Mature B Cells into Stem Cell Like State

Scientists Reprogram Fully Mature B Cells into Stem Cell Like State

GEN News Highlights

Scientists found that fully mature, differentiated B cells can be reprogrammed to an embryonic stem cell like state without the use of an egg.

In previous research, induced pluripotent stem (IPS) cells had been created from fibroblasts, but it was unknown if they were fully differentiated. Mature B cells have a specific part of their DNA cut out as a final maturation step, giving researchers a way to make sure the resulting IPS cells were not from immature cells.

Similar to the process used to create IPS cells from fibroblast cells, the scientists successfully reprogrammed immature B cells into IPS cells by using retroviruses to transfer four genes (Oct4, Sox2, c-Myc, and Klf4) into the cells’ DNA. An additional factor CCAAT/enhancer-binding-protein-a, however, was needed to nudge mature B cells to be reprogrammed into IPS cells.

The IPS cells from both the mature and immature B cells could be used to create mice. The mice grown from the reprogrammed mature B cells were missing the same part of their DNA as the mature B cells, demonstrating that they were reprogrammed from fully differentiated cells.

This work offers the ability of creating new mouse models for autoimmune diseases such as multiple sclerosis and type 1 diabetes, according to the investigators. For example, mature B or T cells specific for glia could be reprogrammed to IPS cells and then used to create mice with an entire immune system primed to only attack the glia cells, thereby creating a mouse model to study multiple sclerosis.

The researcher was performed by investigators at Whitehead Institute for Biomedical Research and MIT. The study will be published in the April 18 issue of Cell.

$1m for stem cell research

NSW and Victoria join forces to fund stem cell research।

Kate McDonald 11/04/2008 11:42:41

The Victorian and NSW governments have announced a fund of $1 million for a collaborative stem cell research program।

Each state will provide $500,000 to the program, which will require research collaboration between both states, although national and international collaboration is being encouraged।

The grants will also require compliance with legislation involving human embryonic stem cells.
The main aim of the program is to improve the sustainability of techniques, technical expertise and the range of applications for stem cell research and in particular the advancement of somatic cell nuclear transfer (SCNT) techniques.

NSW Minister for Science and Medical Research, Verity Firth, said the new funding, along with regulatory certainty regarding human embryonic stem cell research, will help further research into producing tailored human stem cell lines for therapeutic use।

Guidelines and application forms are available from Business Victoria and the NSW Office for Science and Medical Research

Scientists develop technique to "clean" stem cells

Scientists in Singapore have developed a strategy to "clean up" embryonic stem cells, which researchers hope can one day be used to replace damaged tissues and for other tailor-made personal treatments.

Embryonic stem cells are master cells that can grow, or "differentiate", into any type of cell or tissue, and are subsequently transplanted into the body.
But some studies have shown that residual stem cells that fail to differentiate can turn cancerous later on.

In the journal Stem Cells, scientists in Singapore said they generated antibodies that successfully killed off these residual stem cells in mice.

"Although human embryonic stems cells are a very powerful source to make differentiated cells, like heart cells, the problem is that you can have residual cells and there is a safety concern because they can form ... a mass of tumour cells," said Andre Choo, senior scientist at the Bioprocessing Technology Institute in Singapore.

"So if you give a product that is 95 percent heart cells, but 5 percent embryonic stem cells, it may be a problem later on," he said by telephone.

The researchers managed to generate antibodies in mice after injecting human embryonic stem cells into the animals.

The antibodies were then harvested and added to cultured embryonic stem cells that had been newly differentiated on laboratory dishes.

"It (the antibody) specifically eliminated undifferentiated cells within 30 minutes but left differentiated cells untouched," the researchers wrote.

The mixture was later injected into a batch of mice, while another batch of mice were given untreated stem cells.

After 6 to 8 weeks, the researchers detected tumours in the mice that received untreated stem cells, but those that received the mixture of stem cells and antibodies were free of tumours even after 20 weeks.

"We made antibodies that can kill them (undifferentiated stem cells) ... it acts as a clean up step for you to remove any of these rogue cells or potentially problematic cells," Choo said. (Reporting by Tan Ee Lyn; Editing by Alex Richardson)