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Pluripotent Stem Cell Research | Overview

What are pluripotent stem cells?

The primary groups of cells and tissues that make up the entire human body (except for germ cells) are known as: 

  • Ectoderm – cells that develop into tissues such as skin and the nervous system.
  • Endoderm – cells that give rise to digestive and respiratory organs, such as lung, liver, stomach, and pancreas.
  • Mesoderm – cells that form tissues and organs such as bone, cartilage, blood and blood vessels, muscle, heart, and kidney.

Stem cells play important roles in development, function and repair of our tissues and organs. For example, blood stem cells give rise to all blood cells (e.g., red blood cells, macrophages, platelets, lymphocytes). Pluripotent stem cells are a particularly potent type of stem cell that normally only exists during early embryonic development. What makes pluripotent stem cells so potent is their ability to form all three of the basic body layers (ectoderm/endoderm/mesoderm) and even germ cells. In other words: pluripotent stem cells can potentially produce any cell or tissue the body needs to repair itself. Indeed, many clinical trials are already underway in which cells and tissues made from pluripotent stem cells are being evaluated as treatments or cures for a variety of diseases, including diabetes, Parkinson’s disease, spinal cord injury, blindness, thrombocytopenia, and many others.

What are the different types and of pluripotent stem cells that are being studied at Boston Children’s Hospital?

  • induced pluripotent stem cell (iPS cells) – typically made from skin or blood cells by a process called ‘reprogramming’.
  • conventional embryonic stem cell (ES cells) – typically derived from leftover embryos donated after IVF treatment.
  • nuclear transfer ES cells (ntES cells) – generated from embryos after replacing an egg’s nucleus with that of an adult cell.
  • parthenogenetic ES cells (pES cells) – obtained from embryos produced by an unfertilized egg.

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.

What makes pluripotent stem cells important?

  1. Pluripotent stem cells can be used to create any cell or tissue the body, allowing scientist to study human development and the causes of diseases in a culture dish. Moreover, many of the cell types that can be made from pluripotent stem cells may eventually be turned into safe and effective therapies for diseases including:
    • Diabetes
    • Cystic fibrosis
    • Blindness
    • Spinal cord injury
    • Leukemia
    • Heart disease
  2. Pluripotent stem cells can be customized to ensure a perfect immunological match for any patient. This means that patients could receive transplants of tissue and cells without having to find a suitable tissue donor and without the risk of tissue rejection problems or the need to take powerful immune-suppressing drugs for the rest of their lives.                 
  3. The most potent cell-based therapies of the future are likely to require complex genetic engineering to maximize the efficacy and safety of the therapeutic cells and tissues. Compared to virtually all other cell types (including adult stem cells), it will be much easier – and potentially safer – to perform the necessary engineering steps with pluripotent stem cells.

Chronology and recent highlights of human iPS cell research by Boston Children’s Hospital Stem Cell Program scientists: