2003 Articles
Due to copyright restrictions, the full text of articles linked below is available only to the NIH community. Those outside the NIH community can access citations and abstracts.
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- Scientists Establish Long-Term Viability of Human Embryonic Stem Cells Before human embryonic stem cells (hESCs) can be used to develop human therapies, scientists must first be certain that the cells are safe, stable, and may remain undifferentiated for extended periods of time. NIH intramural scientists from the National Institute on Aging collaborated with Geron Corporation scientists to demonstrate that hESCs from different cell lines share common genetic markers and can be grown under similar laboratory conditions. A second study established that hESCs may be stably kept in an undifferentiated state and do not develop chromosome abnormalities when maintained in long term culture. In both studies, the hESCs were grown without feeder layers, a technique that lessens concerns about cross-species contamination. These studies help establish the potential of hESCs for use in treating human disease and injury. (Developmental Dynamics 229:243–258; Geron Corporation and laboratory of M.S. Rao)
- Donor Spleen Stem Cells Help Recipients Make Insulin
Nonobese diabetic (NOD) mice develop diabetes because they are unable to eliminate self-reactive antibodies during their development. Self-reactive antibodies in the pancreas eventually destroy the mice's insulin-secreting cells, making them unable to break down food sugars. Scientists study NOD mice as a model for human type 1 diabetes. Previous studies demonstrated that treatment with a combination of a factor called TNF-α and adult spleen stem cells from a donor mouse could "cure" NOD mice of their diabetes. The treatment seems to work by eliminating self-reactive antibodies and allowing the mice to regenerate insulin-secreting cells. NIH-supported scientists at Harvard Medical School recently demonstrated that donated spleen stem cells not only help eliminate self-reactive antibodies, but also play a role in the formation of new insulin-secreting cells in the treated NOD mice. This research may enable doctors to develop adult spleen stem cell treatments for humans with type 1 diabetes. (Science 302: 1223–1227, 2003, laboratory of D.L. Faustman)
- Neural Stem Cells Need Bmi-1 to Self-Renew
One important characteristic of stem cells is their ability to both self renew (divide to produce more of themselves) and to produce the progenitor cells that repair or maintain adult organs and tissues. NIH-supported investigators at the University of Michigan determined that neural stem cells need to express the gene Bmi-1 in order to self-renew. Cultured neural stem cells that lack Bmi-1 have a diminished capacity to self-renew. Mice that lack Bmi-1 appear normal at birth but their supply of neural progenitors is rapidly used up, and they develop nervous system defects. Scientists may eventually be able to use this knowledge to help restore self-renewal capabilities to human adults' stem cells. (Nature 425:962–967, 2003, laboratory of S.J. Morrison)
- Donor Bone Marrow Stem Cells Fuse with Recipient Cells
Scientists do not agree on exactly how adult bone marrow stem cells contribute to regeneration or repair of tissues and organs in human beings. Some research suggests that these adult stem cells change their identities (becoming heart muscle cells, brain cells, or liver cells, for example) and other research suggests that the stem cells fuse with existing cells. A multinational NIH-supported research team used a very precise technique to determine that stem cells from donor mouse bone marrow fuse with nerve cells, heart muscle cells, and liver cells in the recipient mice. This study provides strong evidence that some reports describing the ability of adult bone-marrow-derived stem cells to assume nerve, heart muscle, or liver cell identities may instead be due to cell fusion. (Nature 425:968–973, 2003, laboratory of A. Alvarez-Buylla)
- Culturing Human Embryonic Stem Cells in 3-D
A team of NIH-supported scientists from the Massachusetts Institute of Technology and Israel's Rambam Medical Center constructed 3-dimensional scaffolds in culture to encourage human embryonic stem cells (hESCs) to grow into specific shapes. By varying growth conditions, the scientists coaxed the hESCs to form 3-D structures with characteristics of developing liver tissue, cartilage, nerve, or blood vessels. This technique may permit scientists to generate hESC-derived tissue in the laboratory for use in skin grafts, wound treatment, or organ transplantation. (Proceedings of the National Academy of Sciences of the USA 100:12741–12746, 2003, laboratories of J. Itskovitz-Eldor and R. Langer)
- Survival Gene Helps Bone Marrow Stem Cells Repair Rat Heart
A heart attack kills heart muscle cells and reduces the heart's ability to pump blood. Although transplanted bone marrow stem cells can restore some of the hearts' blood pumping abilities, the actual improvement seen is small. Scientists believe this may be because many of the cells die after they are transplanted. Non-NIH funded scientists at Brigham and Women's Hospital and Harvard Medical School used a virus to overexpress a survival gene called Akt in rat bone marrow stem cells. When transplanted into the hearts of rats that had suffered a heart attack, the Akt-overexpressing bone marrow stem cells restored four times more pumping ability than did cells without Akt. This work may lead to improved bone marrow stem cell treatments for human heart attacks. (Nature Medicine 9:1195–1201, 2003, laboratory of V.J. Dzau)
- Mouse Embryonic Stem Cells Develop Into Sperm
Japanese-funded researchers were able to coax male mouse embryonic stem cells into becoming germ cells, which have the potential in males to produce sperm or in females to produce egg cells. When transplanted into mouse testis, the male germ cells gave rise to mature sperm. If these results can be repeated with human embryonic stem cells, scientists would have a valuable new source of cells to study how human germ cells and sperm cells are specified. A better understanding of how sperm are generated may lead to new treatments for male infertility. (Proceedings of the National Academy of Sciences of the USA 100:11457–11462, 2003, laboratory of T. Noce)
- Donor Blood Vessel Stem Cells Prevent Atherosclerosis in Recipient Mice
NIH-supported investigators at Duke University discovered that endothelial progenitor cells (cells that line the blood vessels) from young donor mice were able to prevent fatty buildup in the arteries (atherosclerosis) of recipient mice that were fed a high fat diet. The researchers also found that older mice make less desirable donors because they have fewer endothelial progenitor cells capable of blood vessel repair. They hypothesize that a gradual reduction in this cell type may explain age-related increases in atherosclerosis. Scientists may be able to use information learned from this work in mice to develop ways to restore endothelial progenitor cells to treat and/or prevent atherosclerosis in humans. (Circulation 108:457–463, 2003, laboratory of D.A. Taylor)
- Muscle Stem Cells
Satellite cells are adult stem cells found in muscle tissue that divide in response to injury to generate both more stem cells and new muscle cells. Scientists supported by the NIH recently identified a molecular signaling pathway that "turns on" these cells' muscle-forming processes—that is, it causes the satellite cells to generate more muscle cells. The pathway, known as the Wnt signaling pathway, is now a potential target for drug development to treat muscle wasting diseases. (Cell 113:841–852, 2003, laboratory of M.A. Rudnicki)
- Human Embryonic Germ Cells Restore Movement to Paralyzed Rats
Using pluripotent cells derived from human embryonic germ cells, scientists not funded by the NIH have been able to partially restore paralyzed rats' ability to move. The rats serve as an animal model of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Transplanted pluripotent cells migrate into the spinal cord of paralyzed rats and prevent existing host neurons from dying. The cells seem to restore mobility by secreting factors that promote the regrowth of connections between ingrowing nerves and motor neurons. This work provides hope that scientists may one day be able to use pluripotent cells to restore movement to patients suffering from Lou Gehrig's disease. (The Journal of Neuroscience 23:5131–5140, 2003, laboratories of J.D. Gearhart and J.D. Rothstein)
- Identification of a Gene Critical to Self-Renewal in Stem Cells
Two papers published together in volume 113 of the journal Cell brought scientists closer to the ultimate goal of identifying the molecular factors that give stem cells their ability to self-renew and maintain pluripotency. Researchers supported by Japanese funds recently identified a gene specifically expressed in mouse embryonic stem cells and preimplantation embryos. They provide evidence that the product of this gene, called nanog, is a homeobox transcription factor that plays a role in preventing differentiation and is critical to maintaining pluripotency in mouse embryonic stem cells. (Cell 113:631–642, 2003, laboratory of S. Yamanaka) Scientists supported by funds from the United Kingdom identified a gene present in both mouse and human embryonic stem cells, and lacking in differentiated cells. They named the gene nanog, after the mythological Celtic land of eternal youth, Tir nan Og. The researchers demonstrated that Nanog is important for maintaining the self-renewing properties of mouse embryonic stem cells and is expressed in the cells of the early embryo that are used to derive embryonic stem cells. They provide evidence that Nanog acts independently of another signal transduction pathway important to maintaining the pluripotency of stem cells, which involves the activation of Stat3. (Cell 113:643–655, 2003, laboratory of A. Smith)
- Mouse Embryonic Stem Cells Can Form Oocyte-like Cells
Using mouse embryonic stem cells, NIH-supported researchers at the University of Pennsylvania have succeeded in generating mouse oocyte-like cells in vitro. The oocytes developed into structures resembling blastocysts in the petri dish without being fertilized (parthenogenesis). If this work could be repeated with human embryonic stem cells (hESC), it would have important implications for: creation of new hESC lines, generation of tissue for transplantation, generation of human oocytes, and infertility treatment. (Science 300:1251–1256, 2003, laboratory of H.R. Schöler)
- Human Feeder Layers
Until recently, all human embryonic stem cells were grown on mouse feeder layers. Now scientists are establishing conditions that allow human embryonic stem cells to grow in the presence of human feeder cell layers. NIH-supported scientists in the United States, using stem cells eligible for federal research funding, have tested the ability of human feeder cells derived from fetal or adult tissues to support the growth of human embryonic stem cell lines. Both fetal and adult human feeder cells were able to support and maintain the cells in an undifferentiated state. (Stem Cells 21:131–142, 2003, L. Cheng et al.)
- Stem Cells in Baby Teeth
NIH intramural scientists at the National Institute of Dental and Craniofacial Research (NIDCR) recently characterized a population of stem cells found in the dental pulp of deciduous, or "baby" teeth. These stem cells have the potential to become cells expressing molecular markers characteristic of dentin, bone, fat, and nerve cells and may provide an acessible source of stem cells to repair damaged teeth, regenerate bone, and treat nerve injury or disease. (Proceedings of the National Academy of Sciences of the USA 100:5807–5812, 2003, laboratories of P.G. Robey and S. Shi)
- Glial Stem Cells Can Produce Neurons in Culture
NIH-supported researchers in New York recently identified a population of glial progenitor cells in the human adult brain capable of generating both neurons and glia in culture. This work suggests that it is the cells' environment within the brain, rather than a loss of potential, that prevents the cells from generating neurons. This conclusion has critical implications for those attempting to regenerate or repair nervous tissue in human beings. (Nature Medicine 9:439–447, 2003, laboratory of S.A. Goldman)
- Homologous Recombination in Human Embryonic Stem Cells
NIH-supported researchers at the University of Wisconsin recently succeeded in replacing a targeted stretch of DNA in human embryonic stem cells (hESC). This study used a well-known mechanism of genome targeting called homologous recombination, which has been used for more than ten years to target specific genes in mouse ES cells. This important study opens the door to scientists who want to study the function of specific genes within human ES cells and also provides a way to modify hESC-derived tissues for use in treating patients. (Nature Biotechnology 21:319–321, 2003, T.P. Zwaka and J.A. Thomson)
- Bone Marrow Stem Cells Can Produce Nerve Cells
NIH-supported researchers at the University of Minnesota recently reported that single adult stem cells derived from rodent bone marrow were able to differentiate into both neuron and glial cells and offspring of these adult stem cells were found in most parts of the brain. This study provided more evidence of adult stem cell pluripotency. (Cell Transplant 12:201–213, 2003, laboratories of C.M. Verfaillie and W.C. Low)
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