- Induced pluripotent cells (iPS cells)
Scientists have discovered ways to take a somatic cell (an ordinary cell, such as a skin fibroblast) and reprogram (convert) it into a pluripotent cell using reprogramming factors. The most frequently used reprogramming factors are four transcription factors called OCT4, SOX2, KLF4, and c-MYC that work together to turn off the somatic cell specific genes and turn on the genes expressed by pluripotent cells. These reprogrammed cells are known as induced pluripotent, or iPS, cells. The Stem Cell Program at Boston Children's was one of the first three research centers to successfully reprogram human cells into iPS cells, an accomplishment cited as the Breakthrough of the Year in 2008 by the journal, Science.
At Boston Children’s Hospital, iPS cells are being used to study what makes stem cells special, how they mature into different cell and tissue types, and how complex tissue structures and organs develop. The ease at which iPS cells can be generated from any healthy donor or patient make them a particularly powerful tool to study the root causes and mechanisms of diseases. Indeed, the Stem Cell Program at Boston Children’s Hospital was the first stem cell research center that developed iPS cell lines for a variety of diseases, including diabetes, Parkinson’s disease, Huntington’s disease, severe-combined immune deficiency, Down syndrome, and many more.
- Embryonic stem cell (ES cells)
Scientists use the label ‘embryonic stem cell’, or ES cell, as a general term for pluripotent stem cells made from very early (pre-implantation stage) embryos. Conventional ES cells are derived from embryos produced by in vitro fertilization (IVF), a common type of infertility treatment. In IVF, human egg cells are collected and then fertilized by sperm cells in a culture dish. IVF often produces embryos that end up not getting implanted to achieve a pregnancy because implanting too many embryos at the same time is risky. These unused embryos are sometimes frozen for future use, sometimes made available to other couples undergoing fertility treatment, and sometimes they are simply discarded.
Several couples have chosen instead to donate their leftover embryos to stem cell research. The donated embryos are then placed in a media preparation and incubated to allow them to develop for a few days. By about the fifth day the fertilized egg will have developed into a blastocyst – a pre-implantation stage embryo that consists of about 100-200 cells. At this stage, ES cells are derived from the blastocyst’s inner cell mass. Researchers from the Stem Cell Program at Boston Children’s Hospital were the first to show that high-quality ES cells can be obtained from donated embryos that were deemed unsuitable for use in fertility treatment due to their failure to thrive during in vitro culture.
- Stem cells made from nuclear transfer embryos (ntES cells)
In procedures called “somatic cell nuclear transfer” (SCNT), the genetic material of an egg cell is replaced with that of a somatic cell (somatic cell means any of the developed human body other than a germ cell). These ‘nuclear transfer’ eggs contain the complete set of chromosomes from the somatic cell. The transferred genetic material from the somatic cell gets reprogrammed by the egg and acquires a ‘totipotent’ state. As with fertilized eggs during IVF, nuclear transfer eggs can be allowed to divide and mature in a culture dish until they form a blastocyst. Scientists can then make a type of pluripotent stem cell called a somatic cell nuclear transfer ES cell (sometimes called an ntES cell) from these blastocysts. This technique has been used to make ntES cells from mouse and human skin cells. Like iPS cells, the nuclear genetic material of ntES cells matches that of the donor/patient from whom the somatic cells were obtained, meaning that therapeutic cells made from these ntES cells can be used to treat genetically matching patients without risk of rejection or need to take immunosuppressive drugs.
- Stem cells from unfertilized eggs (parthenogenetic embryonic stem cells)
Through chemical treatments, eggs can be induced to develop into embryos even in the absence of fertilization, in a process called parthenogenesis. While these embryos are not viable, they can nevertheless develop into blastocytst-stage embryos from which parthenogenetic embryonic stem cells (pES cells) can be derived. If this technique is proven safe it could become yet another method by which a person may be able to donate their own cells (in this case, eggs) to create pluripotent stem cells that match them genetically, thus avoiding the risk of immunological rejection of therapeutic cells made from these types of stem cells.