Embryo Project Encyclopedia

Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.

Matthew Kaufman was a professor of anatomy at the University of Edinburgh, in Edinburgh, UK, who specialized in mouse anatomy, development, and embryology during the late twentieth century. According to the The Herald, he was the first, alongside his colleague Martin Evans, to isolate and culture embryonic stem cells. Researchers initially called those cells Evans-Kaufman cells. In 1992, Kaufman published The Atlas of Mouse Development, a book that included photographs of mice development and mice organs over time. Kaufman also wrote books about UK medical history, phrenology, or the study of craniums as an indicator of character or mental ability, and medical teaching in the eighteenth and nineteenth centuries. Kaufman’s anatomical records and experiments in mouse development contributed to genetic engineering, embryology, and anatomy.

In 1893, Julia Barlow Platt published her research on the origins of cartilage in the developing head of the common mudpuppy (Necturus maculosus) embryo. The mudpuppy is an aquatic salamander commonly used by embryologists because its large embryonic cells and nuclei are easy to see. Platt followed the paths of cells in developing mudpuppy embryos to see how embryonic cells migrated during the formation of the head. With her research, Platt challenged then current theories about germ layers, the types of cells in an early embryo that develop into adult cells. In most organisms' development, three types of germ layers are responsible for the formation of tissues and organs. The outermost layer is called ectoderm, the middle layer mesoderm, and the innermost layer endoderm, although Platt called it entoderm. Platt's research provided a basis for scientists to clarify the destination or function of the germ layers in vertebrates' development.

In the twentieth and early twenty-first centuries, Gail Roberta Martin specialized in biochemistry and embryology, more specifically cellular communication and the development of organs. In 1981, she named any cell taken from inside a human embryo at the blastocyst stage an “embryonic stem cell”. During development, an embryo goes through the blastocyst stage just before it implants in the uterus. Embryonic stem cells are useful for experiments because they are self-renewing and able to develop into almost any cell type in the body. Martin later identified a key chemical component in limb development and continues to study embryogenesis, or the growth of embryos over time. Martin’s work on embryonic stem cells has allowed scientists to further research and treat human diseases, and her study of how organs form has helped scientists learn about the healthy growth of embryos.

Shoukhrat Mitalipov, Masahito Tachibana, and their team of researchers replaced the mitochondrial genes of primate embryonic stem cells via spindle transfer. Spindle replacement, also called spindle transfer, is the process of removing the genetic material found in the nucleus of one egg cell, or oocyte, and placing it in another egg that had its nucleus removed. Mitochondria are organelles found in all cells and contain some of the cell’s genetic material. Mutations in the mitochondrial DNA can lead to neurodegenerative and muscle diseases. Mitalipov and Tachibana used spindle replacement to produce healthy offspring from an egg with mutated mitochondria in rhesus macaques (Macaca mulatta). The experiment showed that spindle transfer eliminated the chance of transmission of mitochondrial diseases from the affected primates to their offspring, offering the potential to eliminate mitochondrial diseases in humans.

According to the US National Institutes of Health (NIH), the standard American source on stem cell research, three characteristics of stem cells differentiate them from other cell types: (1) they are unspecialized cells that (2) divide for long periods, renewing themselves and (3) can give rise to specialized cells, such as muscle and skin cells, under particular physiological and experimental conditions. When allowed to grow in particular environments, stem cells divide many times. This ability to proliferate can yield millions of stem cells over several months. As long as the stem cells remain unspecialized, meaning they lack tissue-specific structures, they are able to sustain long-term self-renewal.

In 2009, Shoukhrat Mitalipov, Masahito Tachibana, and their team of researchers developed the technology of mitochondrial gene replacement therapy to prevent the transmission of a mitochondrial disease from mother to offspring in primates. Mitochondria contain some of the body's genetic material, called mitochondrial DNA. Occasionally, the mitochondrial DNA possesses mutations. Mitalipov and Tachibana, researchers at the Oregon National Primate Research Center in Beaverton, Oregon, developed a technique to remove the nucleus of the mother and place it in a donor oocyte, or immature egg cell, with healthy mitochondria. The resulting offspring contain the genetic material of three separate individuals and do not have the disease. Mitalipov and Tachibana's technology of mitochondrial gene replacement built on decades of research by different scientists and enables researchers to prevent the transmission of human mitochondrial diseases from mother to offspring.

In 2015, biologist Helena D. Zomer and colleagues published the review article “Mesenchymal and Induced Pluripotent Stem Cells: General Insights and Clinical Perspectives” or “Mesenchymal and Induced Pluripotent Stem Cells” in Stem Cells and Cloning: Advances and Applications. The authors reviewed the biology of three types of pluripotent stem cells, embryonic stem cells, or ESCs, mesenchymal stem cells, or MSCs, and induced pluripotent stem cells, or iPS cells. Pluripotent stem cells are a special cell type that can give rise to other types of cells and are essential for development. The authors describe the strengths and weaknesses of each type of stem cell for regenerative medicine applications. They state that both MSC and iPS types of stem cells have the potential to regenerate tissues among many other therapeutic possibilities. In their article, Zomer and colleagues review the potential for MSCs and iPS cells to reshape the field of regenerative and personal medicine.

Thomson, et al. v. Thompson, et al. was a lawsuit filed in the United States District Court for the District of Columbia on 8 May 2001 as Civil Action Number 01-CV-0973. This lawsuit was filed in hopes of gaining injunctive relief against a moratorium on the federal funding of stem cell research. The plaintiffs in the case were seven prominent scientists who performed embryonic stem cell research and three patients: James Thomson, Roger Pedersen, John Gearhart, Douglas Melton, Dan Kaufman, Alan Trounson, Martin Pera, Christopher Reeve, James Cordy, and James Tyree. The suit was filed against Tommy G. Thompson in his official capacity as Secretary of the Department of Health and Human Services; Ruth Kirschstein in her official capacity as Acting Director of the National Institutes of Health; the Department of Health and Human Services (HHS); and the National Institutes of Health (NIH). The plaintiffs argued that by illegally delaying and withholding federal funds for stem cell research, the defendants were causing irreparable harm to research and development of potential therapies for patients.There was also concern about potentially preventing young researchers from entering the field, and restricting the sharing of discoveries between scientists that federal funding of scientific research fosters.