Pluripotent Stem Cell Research

Research on embryonic stem cells at Children’s Hospital Boston

The Stem Cell Program is pursuing various approaches to creating embryonic stem cells (ES cells) in parallel -- using embryos from in vitro fertilization (IVF) donated under strict ethical criteria, nuclear transfer and parthenogenesis. Each method has its advantages and disadvantages, but by studying them all, scientists can get the greatest understanding of how stem cells work and how to maximize their treatment potential.

Eleven new NIH-approved human ES cell lines have been created at Children’s Hospital Boston from donated IVF embryos. All of these lines were created through the use of poor-quality embryos that are typically discarded as part of the IVF process.

Safety and efficiency:
To help make embryonic stem cells more viable for research and treatment purposes, researchers in the Stem Cell Program,are seeking to better understand them and refine techniques for making them. These efforts include:

  • Finding efficient ways to differentiate human embryonic stem cells into different types of specialized cells, beginning with blood stem cells.
  • Creating human embryonic stem cells through nuclear transfer and parthenogenesis.
  • Seeking less technically cumbersome, more efficient ways to create ES cells through nuclear transfer.
  • Exploring the safety of embryonic stem cells made through parthenogenesis (pES cells). These cells have altered expression of certain “imprinted” genes that are turned “on” or “off” based on which parent they come from. pES cells, made from eggs alone, carry only maternally imprinted genes. Altered expression of imprinted genes has been linked with cancer and poor growth in some tissues. In addition, pES cells may have duplicated copies of mutant genes that have been linked with malignancies or abnormal tissue growth.
  • Pinpointing how embryonic stem are able toself-renewal and generate many different cell types, using a comprehensive genomics approach to identify the important regulatory factors and their interactions.
  • Exploring the role of tiny bits of genetic code in known as regulatory RNAs in the self-renewal and pluripotency of ES cells, and their relevance to human disease.

Embryonic stem cell milestones at Children’s:

Researchers at Children’s were the first to transform embryonic stem cells (ES cells) from mice into blood stem cells, showing that these cells can be manipulated in the lab to create different kinds of tissues.

Children’s researcher George Daley, MD, PhD, then at the Whitehead Institute, was the first to successfully correct a genetic defect (an immune deficiency) with embryonic stem cells in mice. The research team created the ES cells through nuclear transfer, introduced corrective genes, then differentiated them into blood stem cells and infused them into the mice, partially restoring their immune function. This success, first described in 2002, showed that combined genetic and cell-based therapy can work.

Children’s was also:

  • The first to create genetically matched ES cells in mice by combining parthenogenesis (using eggs alone) with genetic typing to create cells compatible with the recipients’ immune systems, establishing the technique as a potential way to create rejection-proof cell-based therapies.
  • The first to show that a protein abundant in ES cells, called LIN28, can transform cells to a cancerous state, and is abundant in a variety of advanced human cancers. The finding, reported in 2009, strongly supports the idea that cancer is often a disease of stem cells, and offers a possible new target of attack, particularly in highly resistant and hard-to-treat cancers.
  • The first to transform mouse ES cells into a continuously growing line of embryonic germ cells — a unique group of cells that the embryo sets aside for future reproduction. These cells were then used to create primitive male sperm that, when combined with an egg, were able to createembryos. This work, cited by Science Magazine as a “Top Ten” breakthrough for 2003, has implications for understanding how germ cells mature and how errors in germ-cell formation may lead to birth defects. It may also suggest new approaches to infertility and cancer.

Related work:

The Stem Cell Program is also actively researching induced pluripotent stem cells (iPS cells). Click on the Induced Pluripotent Stem Cells link on the right side of this page to learn more.



    • New ES cell lines

      In June, 2006, Children’s Hospital Boston launched a program to create human embryonic stem cells, using eggs and embryos donated by couples undergoing in vitro fertilization (IVF) at Brigham and Women’s Hospital. To date, Children’s has created 11 lines that are eligible for federal funding. These lines were all derived from poor-quality embryos that would otherwise have been discarded, and are currently being used for research purposes. Children’s is making them available to scientists around the world.

    • The Zebrafish Genome Project

      A complex control network of signals in stem cells and their environment regulates the cells’ unique characteristic of “stemness.” With the help of fast-breeding, easy-to-study zebrafish and genomics techniques, researchers in the Stem Cell Program at Children’s Hospital Boston are comprehensively combing the chromosomes to tease out this network. Understanding it in greater detail could give stem cell biologists a new set of tools to coax the maturation of cells. Read more.

    • Embryonic stem cells teach lessons about Fanconi anemia

      Children with Fanconi anemia, a rare genetic disease, often begin experiencing low blood cell counts at about age 7, and can die unless they get a bone marrow transplant. Now, by modeling Fanconi anemia in the lab using human ES cells, researchers at Children’s Hospital Boston reveal that inadequate production of blood cells may actually begin long before birth, casting a whole new light on the disease. ES cells were used because past research has shown Fanconi anemia to be difficult to model with induced pluripotent cells
      . Read more.

    • The stem cell-cancer connection

      Two fundamental processes in biology—stem cell generation and carcinogenesis—are closely related. Richard Gregory, PhD, a principal investigator in the Stem Cell Program at Children’s Hospital Boston, is studying the nature of this link, and uncovering new approaches to enhancing stem cell creation as well as ways to inhibit cancer.