Harvard Stem Cell Research Proceeds with Private Funding

Many tears have been shed over the US federal government's refusal to finance new stem cell lines. Harvard Stem Cell Institute and Children's Hospital Boston have decided to stop crying and start working. Utilising private funding, researchers in Boston are busily starting new stem cell lines, helping to lay the foundations for a major bio-medical revolution.

In this initial protocol, Daley and colleagues hope to obtain failed-to-fertilize eggs and poor-quality embryos. They will then use two methods to create hESCs:

1) Nuclear transfer. This technique involves using a microscopic needle to remove the nucleus from an egg, and replacing this nucleus with a donor nucleus, containing the donor's genetic material, or DNA. The process of transferring the donor nucleus into the egg "reprograms" it, reactivating the full set of genes for making all the tissues of the body. The resulting "reprogrammed" cell is encouraged to develop and divide, and by about day 5, forms a blastocyst--a ball of 50-200 cells. The blastocyst's outer cells are destined to become the placenta, while the inner cells have the potential to form all of the tissues of the body. At this point, development is halted and the inner cells are isolated to derive hESCs. Because the nucleus implanted into the egg contained the patient's DNA, the hESCs derived by this method are genetically matched to the patient.

In the future, under separately approved protocols, Daley and colleagues hope to obtain donor cells from actual patients, and to transfer the donor nucleus into a fresh egg from a donor or from the patient herself, if female. The donor cell would be of a type easy to obtain, such as a skin cell.

For now, under the approved study protocol, Daley and colleagues will obtain the donor nucleus from a blastomere, a single cell from a poor-quality embryo of less than 8 days' gestation. They will then transfer this nucleus into a failed-to-fertilize egg, wait for a blastocyst to develop, and isolate hESCs from its inner cell mass.

"Our long-term goal is to create embryonic stem cells from a patient's tissues, correct the genetic defects, and get the repaired cells back into the patients," Daley says. "In the meantime, however, using an embryonic cell rather than a skin cell will increase the chances that nuclear transfer will be successful, because the nucleus of an embryonic cell is much easier to reprogram than the nucleus of a skin cell. This will allow us to answer some basic questions of stem cell biology while becoming technically proficient in creating stem cell lines."

2) In a second technique, hESCs will be created directly from poor-quality embryos, and eventually from frozen, good-quality embryos, without nuclear transfer. The researchers will add feeder cells, chemicals and growth factors to encourage the embryo to grow to the blastocyst stage. They will then stop development and derive hESCs from the blastocyst's inner cell mass. This procedure will generate "generic" hESC lines -- not customized to an individual -- that can be used to study how stem cells behave and differentiate.

Leonard Zon, MD, director of Children's Stem Cell Program, Chair of HSCI's Executive Committee, and Chair of the State Biomedical Research Advisory Committee that oversees Human Stem Cell Research in Massachusetts, was responsible for orchestrating the institutional and administrative oversight and review structures that have allowed the work to be done at Children's. "The work, if successful, will have a major impact on our understanding of human development and tissue formation, and will provide a scaffold for the treatment of many diseases of children and adults," Zon says. Zon also emphasizes that the program explicitly prohibits using these techniques for reproductive purposes - that is, to clone a human being, or to grow one from a donated embryo. "There will be no transfer of cloned embryos to a womb, and no embryo will be allowed to grow beyond the blastocyst stage."

Future goals

In the future, the Daley laboratory hopes to combine hESC creation with gene therapy to treat patients with specific genetic defects. Already, the lab has restored immune function in mice with a severe immune deficiency (similar to "boy in the bubble" disease) by making ESCs through nuclear transfer, correcting the gene defects, differentiating the repaired cells into blood stem cells, and returning the normal blood cells back to the mice. Using similar methods, Daley's team is also treating mice with thalassemia, a disorder of red blood cells that leads to chronic anemia and the need for children to undergo a lifetime of blood transfusions Other research goals of Daley's lab include:

* Using hESCs to create human embryonic germ cells -- primitive cells in the embryo that mature to become sperm or eggs. Daley's lab has already made sperm precursors from mouse ESCs -- work cited by Science Magazine as a "Top Ten" breakthrough for 2003 -- and now, with funding from the Harvard Stem Cell Institute, hopes to create eggs. These eggs could potentially be used in place of donor eggs for nuclear transfer.
* Understanding the process by which nuclear transfer genetically "reprograms" cells back to their embryonic state. This understanding may enable scientists to take mature, specialized cells back to a fully undifferentiated state, without the need for embryos, eggs, nuclear transfer or ESCs.
* Probing the links between stem cells and cancer. Critics of embryonic stem cell research have raised concerns that implanting ESCs in the body could lead to cancer, because when ESCs are injected into mice, they form benign tumors. Daley's lab is studying the conditions under which such tumors could become malignant.
Source: Children's Hospital Boston

The US is the largest donor nation for private charities and international relief efforts, in terms of private funding. It should not be surprising that in the presence of a genuine humanitarian need, private funding would step forward and assist in this important work. Too many institutions become dependent upon support from tax collections, rather than being creative in fundraising. The US government, and most other governments, are too large and omnipresent in the activities of citizens. Eventually humans will be intelligent enough to do away with these institutions of waste, corruption, and quasi-organised criminal activity called governments. Many people have looked forward to that day for a long time.