The science of stem cells

The science of stem cells

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Since 1998, when human pluripotent stem cells were first isolated, research on stem cells has received much public attention, both because of its extraordinary promise and because of relevant legal and ethical issues. Underlying this recent public scrutiny is decades of painstaking work by scientists in many fields, who have been deciphering some of the most fundamental questions about life with the goal of improving health.

In the last several decades, investments in basic research have yielded extensive knowledge about the many and complex processes involved in the development of an organism, including the control of cellular development. But many questions remain. How does a single cell—the fertilized egg—give rise to a complex, multi-cellular organism? The question represents a fundamental challenge in developmental biology. Researchers are now seeking to understand in greater detail the genetic factors that regulate cell differentiation in early development.

Put simply, stem cells are self-renewing, unspecialized cells that can give rise to multiple types all of specialized cells of the body. The process by which dividing, unspecialized cells are equipped to perform specific functions—muscle contraction or nerve cell communication, for example—is called differentiation, and is fundamental to the development of the mature organism. It is now known that stem cells, in various forms, can be obtained from the embryo, the fetus, and the adult.

How and whether stem cells derived from any of these sources can be manipulated to replace cells in diseased tissues, used to screen drugs and toxins, or studied to better understand normal development depends on knowing more about their basic properties. In this respect, stem cell research is in many ways no different than many other areas of modern biology; it is advancing because new tools and new knowledge are providing the opportunities for new insights. Like all fields of scientific inquiry, research on stem cells raises as many questions as it answers.

Highlights of Stem cell research.
Abstracts of selected articles describing the state of the science in stem cell research.

2007 Articles

Found: Stem Cells Responsible for Pancreatic Cancer
Scientific data has shown that the ability of a tumor to grow and spread is dependent on a small group of rogue cells within the tumor, called cancer stem cells. Finding these stem cells is particularly critical for individuals with pancreatic cancer, which has the worst survival rate of any major cancer type. Fortunately, for the first time, privately¬ supported scientists have identified a small population of human pancreatic cancer stem cells. The scientists examined tissue samples from 10 separate pancreatic cancer tumors. The samples then were implanted into mice and aggressively drove tumor formation. When the tumors were examined, the scientists were able to isolate cells that express the characteristics and cellular markers found in stem cells. These pancreatic cancer stem cells composed 1 percent of the total cell population in the tumors grown in the mice. This discovery will help scientists to develop therapeutic approaches to treat pancreatic cancer. Cancer Research 67(3):1030–7, laboratory of D. Simeone. 2007 Feb 1.

Mother"s Stem Cells Passed to Baby—Suggests Possible Way to Treat Diabetes
In type 1 diabetes, an individual"s immune system attacks and destroys their own insulin-producing beta cells in the pancreas. Insulin is necessary to efficiently metabolize sugars in foods, and without it, individuals with diabetes must inject themselves with insulin to survive. Scientists are trying to determine why the body attacks its own beta cells, with the hope of developing treatments to halt or reverse the disease process. Umbilical cord blood specimens from male infants contain female cells, believed to cross the placenta from the mother to the child during pregnancy. NIH-funded scientists designed a study to test the hypothesis that in type 1 diabetes, too many maternal cells cross the placenta, contribute to organs in the developing fetus, and stimulate the child"s immune system to attack those organs after the child is born. The scientists developed a method for identifying non-child (maternal) DNA in cells and tissues and used it to examine blood samples from individuals with type 1 diabetes, from their siblings who do not have diabetes, and from unrelated healthy individuals. Blood samples from individuals with type 1 diabetes contained more maternal cells than blood from their siblings without diabetes, and significantly higher numbers of maternal cells than in blood from unrelated healthy individuals. The scientists next examined male pancreatic autopsy specimens of children or infants for evidence of maternal cells. Although they found more maternal cells in one specimen from a child with diabetes, the cells did not seem to be under autoimmune attack. Instead, the evidence suggested that the mother"s cells had become functional beta cells, helping the child produce insulin after the loss of his own beta cells. The scientists concluded that rather than initiating an immune system attack in individuals with type 1 diabetes, the maternal stem cells may instead increase in number and migrate to the pancreas to replace lost beta cells. They theorize that the child"s body tolerates the maternal cells because the immune system is still developing at the time of maternal cell entry into the child"s body. They are now investigating this process, and hope to one day use maternal stem cells to treat children with type 1 diabetes. Proceedings of the National Academy of Sciences of the USA 104(5):1637–42, laboratory of E.A.M. Gale. 2007 Jan 30.

Stem Cell Lines Generated from Amniotic Fluid
Amniotic fluid surrounding the developing fetus contains cells shed by the fetus and is regularly collected from pregnant women during amniocentesis. Scientists have previously reported that some of these cells can differentiate into fat, muscle, bone, and nerve cells. Now, privately funded scientists have generated non-embryonic stem cell lines from cells found in both human and rat amniotic fluid. They named the cells amniotic fluid-derived stem cells (AFS).
Tests demonstrate that AFS can produce cells that originate from each of the three embryonic germ layers. The cells are self-renewing and maintain the normal number of chromosomes after a long time in culture. However, undifferentiated AFS did not make all of the proteins expected in pluripotent cells, and they were not capable of forming a teratoma. The scientists developed in vitro conditions that enabled them to produce nerve cells, liver cells, and bone-forming cells from AFS. AFS-derived human nerve cells could make proteins typical of specialized nerve cells and were able to integrate into a mouse brain and survive for at least two months. Cultured AFS-derived human liver cells secreted urea and made proteins characteristic of normal human liver cells. Cultured AFS-derived human bone cells made proteins expected of human bone cells and formed bone in mice when seeded onto 3-D scaffolds and implanted under the mouse"s skin. Although scientists do not yet know how many different cell types AFS are capable of generating, AFS may one day allow scientists to establish a bank of cells for transplantation into human beings. Nature Biotechnology 25(1):100–6, laboratory of A. Atala. 2007 Jan.

Tissue-Matched Stem Cells Created in Mice without Cloning
Scientists have proposed the use of somatic cell nuclear transfer (SCNT) to create stem cells that are tissue-matched to an individual. This process is also known as therapeutic cloning. However, due to exchange of genetic information between pairs of like chromosomes (homologous recombination) during the egg"s meiosis, the stem cells created using this method may still not be a precise match for the nucleus donor. In an attempt to improve the degree of tissue-matching, scientists recently derived stem cells from a mouse embryo created using a process known as parthenogenesis. Parthenogenesis describes an embryo created without fertilization of the egg by a sperm, thus omitting the sperm"s genetic contributions. The scientists identified stem cell lines retaining the identical «self» genetic information of the egg donor and used them to generate tissues for transplantation into the egg donor. These transplanted tissues were not rejected by the egg donor mouse"s immune system. If scientists can repeat this technique using human eggs, they may be able to generate tissue-matched cells for transplantation to treat women who are willing to provide their own egg cells for this purpose. This technique could also offer an alternative method for deriving tissue-matched human embryonic stem cells that does not require destruction of a fertilized embryo. Science 315:482–6, laboratory of G.Q. Daley. 2007 Jan 26.

Multipotent Adult Progenitor Cells (MAPCs) Regenerate Blood in Mice
In 2001, scientists isolated a special type of non-blood stem cells from human bone marrow. They named these cells multipotent adult progenitor cells, or MAPCs. MAPCs are able to generate cells of all three embryonic germ layers. Initially, MAPCs were notoriously difficult to isolate and grow in culture. In 2006, scientists reported improved MAPC isolation and culture conditions. Now a collaborative group of NIH-supported scientists successfully used mouse MAPCs to regenerate the blood-forming system in mice. The scientists speculate that MAPCs may arise earlier in development than blood-forming stem cells, because transplanted MAPCs generated both long-term blood-forming stem cells and all types of early blood cells. Although MAPC-derived cells that did not make blood-specific proteins (i.e., not blood cells) were identified in tissues outside of the blood, they also did not make proteins characteristic of the tissue in which they were found. The scientists have not yet determined the identity of these cells. Transplanted MAPC-derived cells did not appear to form tumors in recipient mice. MAPCs" ability to grow and divide in culture and to regenerate the blood-forming system in mice provides hope that scientists may be able to use human MAPCs to treat diseases of the blood. Doctors may also be able to induce transplant tolerance in human beings by using MAPCs to generate both immune cells and tissues for repair or replacement. The Journal of Experimental Medicine 204(1):129–39, laboratory of C. Verfaillie. 2007 Jan 22.