Left: George Q. Daley, HHMI investigator; Douglas A. Melton, HHMI investigator. HHMI scientists and others are exploring the possibilities and limitations of stem cells to understand tissue development with hopes of curing disease.

Not every patient is that lucky. “I just spent the last week in the hospital taking care of kids with all kinds of blood diseases,” says Daley, a physician-researcher at Children's Hospital Boston. “Sickle cell anemia, for example, is exquisitely painful, and we don't have a treatment for it. We give them narcotics and we hydrate them, but what we'd ideally like to do is repair their cells.”

He envisions a day when he'll be able to take cells from his patients, repair the damaged genes, and grow new blood cells to treat them. Daley, a leader in studying stem cells—embryonic stem (ES) cells, adult stem cells, and the tantalizing but still very new induced pluripotent stem (iPS) cells—has already managed to do that kind of cellular repair in mice.

For Daley and others who study stem cells, recent discoveries make this an exciting and challenging time. They are learning how to manipulate these cells to produce the building blocks of various organs. And the development of iPS cells opens the possibility of producing patient-specific stem cells without using human embryos, an achievement that could defuse many of the ethical and political tensions that surround this area of biology. But there is much work to do before researchers know how well these stem cells will deliver on their promise.

		Embryonic stem (ES) cells are derived from embryos that develop from eggs fertilized in vitro. Each embryo, typically four to five days old, is a hollow microscopic ball of cells called a blastocyst. To generate cultures of specific types of differentiated cells—heart muscle cells, blood cells, or nerve cells, for example—researchers change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by inserting specific genes. Through years of experimentation, scientists have established some basic protocols, or “recipes,” for the directed differentiation of embryonic stem cells into specific cell types. Adult stem cells are undifferentiated cells found among the differentiated cells that constitute a tissue or organ. The primary roles of adult stem cells in a living organism are to maintain and repair the tissue where they are found. The adult tissues reported to contain stem cells include brain, bone marrow, skeletal muscle, skin, and liver. Somatic cell nuclear transfer reprograms adult cells, a feat that has been accomplished only with animal cells. An adult cell's nucleus is inserted into an egg cell, which creates an embryo. Stem cells are then derived through a process similar to that used to create embryonic stem cells. Induced pluripotent stem (iPS) cells are derived from adult somatic cells such as skin cells. These cells are reprogrammed, with the insertion of a handful of genes, to act as stem cells. In fact, they then display embryonic stem cell-like abilities.

Photos: Daley: Leah Fasten; Melton: Joshua Dalsimer

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