The results provide new insights into the basic biology of stem cells

The results provide new insights into the basic biology of stem cells -

A team from the University of California researchers, San Diego School of Medicine, Oregon Health & Science University (OHSU) and Salk Institute for Biological Studies has shown for the first time that stem cells created using different methods produce different cells. The findings, published in the July 2, 2014 online edition of Nature provide new insights into the basic biology of stem cells and could ultimately lead to improved stem cell therapies.

Able to develop into any type of cells, pluripotent stem cells offer great promise as the basis for cell transplantation therapies that meet a wide range of diseases and conditions, diabetes and Alzheimer ' Alzheimer cancer and injuries of the emerging spinal cord. In theory, stem cells could be created and programmed to replace sick or absent for all cells of the human body.

The gold standard is human embryonic stem cells (ES cells) grown from discarded embryos generated by in vitro fertilization, but their use has long been limited by ethical and logistical considerations. Scientists have instead turned to two other methods to create stem cells: nuclear transfer of somatic cells (SCNT) in which the genetic material from an adult cell is transferred into an empty egg cell and induced stem cells pluripotent (iPS cells), wherein the adult cells are returned to a stem cell state by turning on artificially targeted genes.

So far, no one had directly and closely compared the stem cells acquired using these methods. The scientists found that they produced different measurable results. "The nuclear transfer ES cells are much more similar to true ES cells, iPS cells," said co-lead author Louise Laurent, PhD, assistant professor in the Department of Medicine of reproduction at UC San Diego. " they are more fully reprogrammed and fewer changes in gene expression and DNA methylation levels that are attributable to reprogramming process itself. "

the development and use of cells iPS has grown exponentially in recent years, largely due to the fact that they can be generated from adult cells (often from the skin) temporarily turning on a combination of four genes to induce adult cells back to a pluripotent state.

Laurent noted that iPS cell lines were established from patients to model many different diseases and "the ability to manufacture custom iPS cells from a patient which could be transplanted back into the patient generated excitement because it would eliminate the need for immunosuppression. "

nuclear transfer method has been developed more recently by a team led by Shoukhrat Mitalipov, PhD, professor and director of the Centre for embryonic cells and gene therapy in Oshu. The technique is similar to that used in the cloning, but pluripotent cells are collected from early embryos before they become mature organisms.

For their comparisons, researchers at UC San Diego and Salk Oshu created four nuclear transfer ES cell lines and seven iPS cell lines using the same skin cells as source of genetic material donor, and then compared them with two types of human embryonic lines. The 13 cell lines were shown to be pluripotent using a standard battery of tests

But closer analysis using powerful genomic techniques to examine the DNA methylation -. A fundamental biochemical process that helps turn genes on and off - and gene expression signatures of each cell line showed key differences in stem cells created using three methods. Specifically, scientists have found that the DNA methylation and expression patterns genes in nuclear transfer ES cells more closely resembled those of ES cells was that iPS cells, which apparently revealed alterations caused by the reprogramming process itself.

"If you believe that gene expression and DNA methylation are important, we do, the closer you get models of embryonic stem cells, the better," said co-senior author Joseph R. Ecker, Ph.D., professor and director of the genomic analysis Laboratory of the Salk. "Right now, the nuclear transfer cells appear closer embryonic stem cells than are iPS cells."

"I think these results show that the method of SCNT is a much better candidate for cell replacement therapies, "said Mitalipov, as a co-lead author of Nature paper. "I really believe that the use of this method of production of stem cells will one day help to cure and treat a wide range of diseases that beat us today."

While nuclear cell transfer may be a better and more accurate representation of the human ES cells, iPS cells, Laurent said there are significant barriers to their adoption and wider application. "Not only technically difficult nuclear transfer, but federal funds can not be used in experiments involving this procedure."

Moreover, she said, the results could stimulate improved iPS methods of cell reprogramming. "Our results showed that cells reprogrammed methods widely used iPS make cells that are similar to standard ES cells in outline, but there are important differences when you look closely. Using the egg cell to do the work, we can get much closer to the real thing. If we can understand what factors lead in the bud the reprogramming process, maybe we can design a better method of iPS cell reprogramming. "