Analysis of a variety of human embryonic stem cell lines determined that the cells originated largely from Caucasian and East Asian populations, with little representation from populations originating in Africa. The lines analyzed are currently in use in research laboratories around the world. In response to these results, scientists from Scripps Research Institute used skin cells from an individual of West African Yoruba heritage to create a new stem cell line, the first to carry the genetic profile of this ethnic group.
Why is this important? Research has shown that discordance between the ethnic origin of organ donors and recipients can influence medical outcomes for tissue transplantation, and that the safety and effectiveness of specific drugs can vary widely depending on ethnic background.
"Ethnic origin is a critical piece of information that should come with every cell line," said Scripps Research Professor Jeanne Loring, who is senior author of the paper resulting from this research. "Everyone who works with stem cells should be doing this kind of analysis."
One of our Sector Companies, International Stem Cell Corp. (ISCO) announced a collaboration with Dr. Jeanne Loring and Scripps Research in November of last year. ISCO has developed a parthenogenetic homozygous stem cell line and is hopeful that this research will provide immune-matched stem cells for human transplant which will allow the building of a "stem cell bank" that could offer on-demand delivery of stem cells matched to a patient’s own immune system.
"Knowing that a big push in the future is using stem cell lines in the clinic and in drug development, there's a need to have an ethnically diverse population of cells," added Louise Laurent, assistant professor at the University of California, San Diego (UCSD) and research associate at Scripps Research, who is first author of the paper with Caroline Nievergelt, also an assistant professor at UCSD.
Greater diversity in cell samples would set the stage for more broadly relevant research by labs in academia and industry, more robust results on the safety and efficacy of potential therapies, and more successful tissue transplants.
Normally, cells develop from stem cells into a myriad of increasingly more specialized cell types during early development and throughout a lifetime. In humans and other mammals, these developmental events are usually irreversible. This means that when tissues are damaged or cells are lost, the body has limited means by which to replenish them.
Having a source of stem cells would be useful in many medical situations because these cells are "pluripotent," having the ability to become any of the body's cell types. Pluripotent stem cells would potentially provide physicians with the ability to replace or repair damaged tissues throughout the body. For example, pluripotent stem cells could be differentiated into the damaged cell type and transplanted.
The Scrips Research analysis included 47 human embryonic stem cell lines collected from labs located around the world—including Korea, Australia, and Finland. The analysis also included five induced pluripotent (iPS) stem cell lines.
To determine the ethnic origins of the stem cell lines and to link them to genetic "signatures" that might affect medical outcomes, the scientists drew on previous research from the International HapMap Project, published in the journal Nature in 2003. This research linked single-letter alterations in the genetic code—known as single nucleotide polymorphisms, or SNPs—with people of known ethnic origins. This data provided a way to identify the ethnic heritage of a donor of any cell.
Laurent noted that simply asking cell donors about their ethnic heritage does not provide accurate data. "There's often an ancestor from a different area who a person doesn't know about," she said.
The technology used for the new study, known as SNP genotyping, uses microarrays, which are easily available, inexpensive, and relatively straight forward for scientists to use.
When the Scripps Research scientists applied the technique to the embryonic stem cell lines, they found that Caucasians were especially well represented among the samples, followed by East Asians. Cells of some mixed heritage were also common. Notably lacking from the samples were cell lines representing African heritage.
In addition, the authors found that the country in which a cell line was generated did not necessarily predict the ethnicity of the donor.
In creating a new pluripotent stem cell line from an individual with a West African Yoruba background, the scientists generated a line that contains distinct genetic markers for disease risk and drug metabolism.
"There's not a lot of value in making a new pluripotent stem cell line now unless it has something new to offer," said Loring. "I think that increasing ethnicity and genetic diversity is an important reason for generating new lines."
The data generated by the study—which Loring describes as the foundation of a new database of human pluripotent stem cell genetic information—will be available for other researchers to access for studies on specific genes, stem cell transplantation, and other topics.
Adapted from the Scripps Research Institute announcement.
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