Thursday, July 3, 2014

Making Good Quality Stem Cells Depends on the Reprogramming Method

Scanning electron micrograph of
human embryonic stem cells (source)
Stem cells offer an enormous promise in emerging cell transplantation therapies.  In theory, they could be used to replace any ailing cells, tissues, or organs in the human body.  In practice, however, available cell types have significant limitations.  For example, embryonic stem cells are considered the "gold standard", but are allogeneic (meaning they are derived from a genetically separate individual) and are occasionally the subject of ethical debates.  Researchers have instead opted for methods of turning adult somatic cells into stem cells, but these are susceptible to epigenetic and transcriptional abnormalities.  A research group from the U.S. looked at whether these abnormalities are intrinsic to somatic cell reprogramming methods.  They ultimately found that stem cells created using different methods produce different types of cells.
Very simplified mechanisms for
the two types of stem cell creation

There are two methods of creating stem cells from adult somatic cells: somatic cell nuclear transfer (SCNT), in which genetic material from an adult cell is transferred into an egg cell (these are called NT-ES cells); and induced pluripotent stem cells (iPS), in which adult somatic cells are reverted back into stem cells by artificially turning on targeted genes - this is also known as a transcription factor-mediated manner of making stem cells.

By examining DNA methylation and other epigenetic effects, which can have a profound impact on gene expression, the authors found that each method of creating stem cells (embryonic, NT-ES, and iPS) resulted in different gene expression signatures.  The DNA methylation and gene expression patterns in NT-ES cells more closely resembled those of the embryonic stem cells than the iPS cells did.  The reprogramming of the cells in the production of iPS is presumed to have caused this problem.  Since SCNT does not require cell reprogramming, epigenetic modifications were less likely to occur.  The epigenetic modifications in iPS cells have the potential to impact the utility of these cells in regenerative medicine, and also in the in vitro modeling of various diseases.

The authors of the study conclude that SCNT is the superior technique for creating stem cells from adult somatic cells used in cell replacement therapies.  However, this method is very difficult, and ethical issues in the U.S. prevent funding of the practice.  Nevertheless, Dr. Shoukhrat Mitalipov of Oregon Health & Science University, one of the co-principal investigators of this study, is confident that SCNT will someday help us cure and treat a number of diseases that leave us stumped today.

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