Quality standard for stem cells
Stem cells created in the laboratory may lack key characteristics
LifeSciencesToday based on UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research: Making quality stem cells
Scientists from the Center for Regenerative Medicine and Stem Cell Research Eli and Edith Brodov of the University of California at Los Angeles have discovered an important natural process in the development of the human embryo, which may be lost when growing embryonic stem cells in the laboratory.
This discovery gives scientists the most important information directly related to the methods of obtaining stem cells for use in regenerative medicine – for organ transplantation and regeneration. In addition, it explains how information coming from an unfertilized egg to an embryo can influence its condition and, consequently, the birth of healthy children.
An article about this discovery was published in the journal Cell Stem Cell (Pastor et al., Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline Memory).
The focus of the American scientists' research was DNA methylation, a biochemical process that naturally occurs in DNA – in the early embryo and in stem cells derived from embryos.
DNA methylation plays an important role in the body's use of genetic information. Proper methylation of certain genes is vital both for normal human development and for maintaining cell health throughout a person's life. In addition, it helps to support the ability of embryonic stem cells to develop into any type of cells in the body.
Researchers have made two important discoveries about DNA methylation. First, they found that an early-stage embryo, or blastocyst, retains the DNA methylation pattern of an egg cell for at least six days after fertilization. Previously, it was believed that the memory of egg methylation persists for only a few hours after fertilization.
"We know that these six days after fertilization are a very important time in human development when there are many changes," says Professor Amander Clark, head of the study. "It is not yet clear why the blastocyst retains methylation during this time period or what purpose it serves, but our discovery opens up new areas in the study of how egg methylation patterns affect the embryo and the birth of healthy children."
The second discovery is that the use of a newly developed method of obtaining stem cells from embryos in the laboratory leads to a loss of methylation.
The blastocyst stage lasts less than five days. Less mature human embryonic cells that exist at the beginning of blastocyst development are called naive embryonic cells. It is believed that by the time of implantation, naive embryonic cells reach a more mature state. Now they are called primed embryonic cells, as they are ready to become any type of cell.
Primed human embryonic stem cells (purple) with one of the surface markers of stem cells (green), which naive embryonic stem cells would not have. (Photo: UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research)
In 1998, when the first human embryonic stem cells were obtained, scientists used a method that gives primed stem cells. Until recently, this method remained standard, but now scientists have started using another technology that allows cells to be kept in a state of naivety.
"For the past three years, naive stem cells have been touted as potentially superior to primed ones," Professor Clark continues. "But our data suggest that the method by which naive stem cells are obtained gives cells with problems, including the loss of methylation of important DNA sites. Therefore, while we do not have a way to obtain more stable naive embryonic stem cells, embryonic stem cells for use in regenerative medicine must be in a primed state so that we can obtain cells of the highest quality for differentiation."
In the near future, Professor Clark and her colleagues plan to determine the optimal conditions for the creation of more stable naive embryonic stem cells that preserve the methylation of genome regions where it is most needed.
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29.03.2016