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Old 11-22-2010, 01:39 PM
Dross Dross is offline
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Default Hebrew University research carries cautionary warning for future stem cell applicatio

Research work carried out at the Hebrew University of Jerusalem arouses a cautionary warning in the growing field of the development of stem cells as a means for future treatment of patients through replacement of diseased or damaged tissues by using the patient's own stem cells. The research indicates a possible danger of cancerous tissue development in the use of such cells.

Embryonic stem cells, which are undifferentiated cells, have the potential to develop into all cell types of the adult body, and thousands of researchers all over the world are working to develop the techniques which will make possible their eventual application.

Research in the field has been carried out initially using embryonic stem cells taken from human embryos. However, a breakthrough occurred when, a number of years ago, Japanese scientists succeeded in creating embryonic-like stem cells from mature human cells through an induced "reprogramming" process. This made it possible to obtain stem cells from a patient which can be used in his or her own treatment, thus avoiding the possibility of cell rejection. These cells are called induced pluripotent stem (iPS) cells.

In order for stem cells to be used in the clinic, however, they must be raised in cultures for an extended period. During this period, it has been observed that embryonic stems cells underwent chromosomal changes, which included changes that characterize cancerous tumor growth.

Research that has been carried out in the laboratory headed by Nissm Benvenisty, the Herbert Cohn Professor of Cancer Research at the Silberman Institute of Life Sciences at the Hebrew University of Jerusalem, has now shown that the iPS cells also undergo abnormal chromosomal changes in culture.

Prof. Benvenisty, together with his post-doctoral fellow Yoav Mayshar and his doctoral student Uri Ben-David, developed a new analytical method for determining the genetic structure of the chromosomes in the iPS cells through determining the cellular patterns of gene expression.

Each cell generally bears two copies of each chromosome in the genome. The Hebrew University researchers discovered that, in time, three copies of chromosomes (trisomy) began to appear in the culture, and that the cells with the extra chromosome were able to rapidly overpower the other, normal cells in the culture. Such trisomies are present in abnormal tissue development, including cancerous growths.

The researchers examined over 100 cell lines which were published by 18 different laboratories around the world, in addition to the iPS cultures raised in their own laboratory, and in this way were able to solidly verify a great number of chromosomal changes in cell lines that until now were considered normal.

In an article published in Cell Stem Cell journal, the Hebrew University researchers have reported their discovery. They noted that the chromosomal changes were not incidental, but rather appeared systematically on chromosome 12 and involved up-regulation of specific genes which reside on that chromosome. This discovery is liable to hinder progress on the development of the use of human iPS cells in future therapy because of the tumorigenic danger involved.

"Our findings show that human iPS cells are not stable in culture, as was previously thought, and require reassessment of the chromosomal structure of these cells," said Prof. Benvenisty. "Also, our work shows for the first time the gene expression changes that accompany these chromosomal aberrations found in the culture, paving the way for our beginning to understand the mechanism by which these changes occur.

"The chromosomal changes in these iPS cells require everyone to exercise great care in continuing to work with them, since these changes apparently will influence the differentiation potential and the tumorigenic risk of these cells."

According to Prof. Benvenisty, "The method we have developed for identifying chromosomal changes through gene expression is likely to serve also in other work involving analysis of different kinds of cells, including cancer cells. It is relatively simple to use and enables one to observe the changes without having to directly analyze the DNA of the cells." The discovery is patented by Yissum, the Technology Transfer Company of the Hebrew University of Jerusalem, which is currently searching for commercial partners for further research and development.

Last edited by gdpawel : 02-04-2013 at 12:11 PM. Reason: posted full article
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Old 11-22-2010, 01:49 PM
gdpawel gdpawel is offline
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Location: Pennsylvania
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Default Embryonic Stem Cell Research in Cancer

According to Robert Weinberg, Ph.D., Professor for Cancer Research at the Massachusetts Institute of Technology (MIT), the "epithelial-mesenchymal transition" (EMT) is a cell-biological behavioral program that operates during the development of normal embryos and is responsible for interconverting one type of cell to another type of cell, more specifically a cell with epithelial properties to one with mesenchymal properties.

An epithelial cell typically sits still and surrounds itself with other epithelial neighbors; without this surrounding company, a typical epithelial cell will quickly die. Epithelial cells line the cavities of all of our organs, including the mouth, lungs, stomach, GI tract, liver, pancreas, prostate, breast milk ducts and so forth.

Mesenchymal cells are, in contrast, typically mobile cells that do not establish stable long-term relationships with their neighbors and are quite resistant to cell death. When a cell passes through an EMT, typically a carcinoma cell that arises from a normal epithelial tissue will acquire mesenchymal traits that confer on it the ability to invade and even to metastasize to distant sites in the body.

Hence by resurrecting a normal cell-biological program, carcinoma cells can acquire an entire suite of traits and ability that make them truly malignant and life-threatening.

Scientists from the University of Manchester, England studied cancer cell movement by using embryonic stem cells to investigate how some tumors are able to migrate to other parts of the body, thereby making cancer treatments more difficult.

Researchers studied a crucial change what makes cancer cells able to start moving and spread into other tissues. That crucial change - known as the epithelial-mesenchymal transition - was observed in the early embryo. It is theorized that embryonic stem cells might undergo a similar process.

They have shown that embryonic stem cells spontaneously change in a manner that is remarkably similar to the epithelial-mesenchymal transition They lose the proteins that cells use to bind to each other and have other protein alterations that are characteristic of spreading cancer cells.

By studying such cells, researchers have identified a novel component of the transition process and expect to identify other factors involved in cancer cell spread, hopefully leading to new cancer therapies.

The findings were published in the journal Molecular Biology of the Cell.

Embryonic Stem Cell Protein Inhibits Melanoma/Breast Cancer

A study by researchers at Northwestern University in Chicage sayd a protein called Lefty that regulates development of human embryonic stem cells can inhibit the growth and spread of deadly melanomas and aggressive breast cancers.

The findings, published in an issue of the Proceedings of the National Academy of Sciences, add to the team's previous efforts to identify the genes and cellular pathways involved in cancer metastasis, and may help lead to new kinds of cancer treatments.

Lefty is secreted only in human embryonic stem cells (hESCs) and not in any other types of stem cells, including those isolated from amniotic fluid, umbilical cord blood or adult bone marrow.

In an earlier study, the Northwestern team found that aggressive melanoma and breast cancer produce a protein called Nodal, which may serve as a marker of aggressive behavior in human cancers.

In this new study, the researchers exposed metastatic melanoma and breast cancer cells to hESCs containing Lefty and noted a dramatic reduction in Nodal production in the cancer cells, along with decreased growth and an increase in programmed cell death (apoptosis).

"The remarkable similarity of the responses of the two tumor types is likely attributable to the commonality of plasticity (for example, the aberrant and unregulated expression of Nodal) that indiscriminately unifies highly aggressive cancer cells, regardless of their tissue of origin.

Further, the tumor suppressive effects of the hESC microenvironment, by neutralizing the expression of Nodal in aggressive tumor cells, provide previously unexplored novel therapeutic modalities for cancer treatment.

Source: Northwestern University
Gregory D. Pawelski

Last edited by gdpawel : 02-04-2013 at 12:10 PM. Reason: additional info
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