Advanced Cell Technology, Inc. (ACT) and its collaborators reported that human oocytes have the capacity to extensively reprogram adult human cells. The research, which appears online ahead of print in the journal Cloning and Stem Cells, demonstrates that although human-to-human clones (human clones) and human-to-animal clones (hybrids) appear similar, the pattern of reprogramming of the donor human cell is dramatically different. In contrast to the human-animal hybrids, the gene expression pattern of the human clones was highly similar to normal human embryos.
Since the cloning of Dolly the Sheep over a decade ago, somatic cell nuclear transfer (SCNT) has been considered a promising way to generate personalized stem cells to repair the body without fear of tissue rejection. Due to the serious shortage of human donor eggs, cows, rabbits, and other animals have long been considered an attractive surrogate source of eggs. Although previous reports have documented the formation of cloned embryos using both human and animal eggs, to date, there has been no data indicating whether—and to what extent—the donor DNA was reprogrammed.
This new study looked at the reprogramming of human cells using eggs obtained from human and animal sources, and shows for the first time that the donor DNA in the cloned human embryos is extensively reprogrammed through extensive up-regulation with similar expression patterns to normal human embryos. Nearly all of the key differentially-expressed genes were activated in the human clones. In distinct contrast, the majority of these genes were down-regulated or silenced in the human-animal hybrids.
“We examined the factors recently used to reprogram skin cells (to induce pluripotent stem cells),” said Robert Lanza, MD, Chief Scientific Officer at ACT, and senior author of the study. “At the center of cellular reprogramming lies the activation of the transcription factors Oct4, Sox2, and nanog. These core factors were activated in both the normal and cloned human embryos. In striking contrast, the human-animal hybrids showed no difference or a down-regulation of these critical pluripotency genes ?effectively silencing them—thus making the generation of stem cells impossible. Without appropriate reprogramming, these data call into question the potential use of animal egg sources to generate patient-specific stem cells. It also renders the moral controversy surrounding the use of human-animal hybrids mute.”
“Producing millions of patient-specific stem cell lines is commercially unviable,” stated William M. Caldwell, CEO and Chairman of ACTC “However, we are optimistic that we will soon have at least two different methods to create stem cells banks to match patients. We estimate that a bank of 100 different lines could furnish a complete tissue (HLA haplotype) match for half of the US population. This will allow us to expand the range of possible clinical therapies to include diseases such as diabetes and heart disease.”
Release Date: February 2, 2009
Source: Advanced Cell Technology, Inc.
Filed Under: Genomics/Proteomics
