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.
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.