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New Hope for Regenerative Medicine

In the issue of G&D, Dr. K. John McLaughlin and colleagues report on their success in using uniparental embryonic stem cells to replace blood stem cells in mice. //Uniparental embryonic stem cells are an appealing alternative source of patient-derived embryonic stem cells, as they have several advantages over embryonic stem cell lines generated by somatic cell nuclear transfer (also known as therapeutic cloning).

Normal mammalian embryos inherit one set of chromosomes from the mother, and one set from the father. Embryos that inherit both sets of chromosomes from the same parent are not viable. They can, however, generate "uniparental" embryonic stem cell lines. Uniparental embryos with two maternal sets of chromosomes are known as parthenogenetic. These embryos have been considered a potential source of embryonic stem cell derived tissues for transplantation into the female from which they were derived.

This study shows for the first time that parthenogenetic blood cells can replace those of an immunocompromised adult mouse. McLaughlin and colleagues also show that this is also possible using embryonic stem cells where both genomes are solely derived from sperm of one male (androgenetic), adding fertile males to the potential patient pool.

Since uniparental ES cells are not derived from viable embryos, their harvesting and use sidesteps many of the ethical concerns that plague traditional ES cell therapies. However, uniparental ES cell research faces the biological hurdle of genomic imprinting, in which specific gene expression patterns are dictated by the parental origin. Uniparental cells only have the imprinting marks for one parental type (or "from one parent") with unknown consequences if harvested and transplanted into adults.

Previous work has shown that uniparental ES cells have only limited ability to contribute to fetal and postnatal development in chimeric animals, with androgenetically-derived uniparenta
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