Programs: Science and Policy
Abstracts of Peer-Reviewed Scientific Papers
Involving Human Embryonic Stem Cells
Directed Differentiation of Embryonic Stem Cells into Motor NeuronsHynek Wichterle, Ivo Lieberam, Jeffrey A. Porter, Thomas Jessell, Cell, August 9, 2002, vol. 110: 385-397 (2002)
Scientists from Columbia University and Curis Inc., administered chemical signals to cultured mouse embryonic stem cells and successfully coaxed the cells to differentiate into functioning motor neurons. The results were built upon ten years of previous research in deciphering the signals that trigger differentiation of motor neurons, which are responsible for controlling the movement of muscles. According to the researchers, the success of the experiments with mouse stem cells suggests that the same type of approach might be used to grow human motor neurons from human stem cells. Future treatments could involve the regeneration of nerve tissue lost to disease or trauma.
Derivation of Oocytes from Mouse Embryonic Stem Cells
Karin Hübner, Guy Fuhrmann, Lane K. Christenson, James Kehler, Rolland
Reinbold, Rabindranath De La Fuente, Jennifer Wood, Jerome F. Strauss III,
Michele Boiani, Hans R. Schöler, Science, May 23, 2002 vol. 300: 1251-1256
A collaborative team of scientists in the United States and France created the first oocytes (mature eggs) directly from mouse embryonic stem cells. Mouse stem cells placed in Petri dishes (without any special growth or transcription factors) grew into oocytes. The results demonstrate that even outside the body, embryonic stem cells remain totipotent, or capable of generating any of the body's tissues. Furthermore, the oocytes developed in this study may be used to create patient-specific cell lines. Lastly, the research may offer insights into understanding and treating infertility.
Derivation of Embryonic Germ Cells and Male Gametes from Embryonic Stem
Niels Geijsen, Melissa Horoschak, Kitai Kim, Joost Gribnau, Kevin Eggan,
George Q. Daley, Nature, January 8, 2004, vol. 427(6970):148-54 (2004)
Researchers at Children's Hospital Boston/Harvard Medical School and the Whitehead Institute for Biomedical Research used embryonic stem cells from mice to create embryonic germ cells (primitive cells in the embryo that mature to become sperm or eggs). Furthermore, the scientists were able to create male sperm that were capable of fertilizing an egg to form an early embryo. The research could provide insights into new ways to treat infertility. In addition, the embryonic germ cells may also aid in understanding the process of cell specialization and how to reprogram adult cells back to their embryonic state.
Committing Embryonic Stem Cells to Early Endocrine Pancreas In VitroHsun Teresa Ku, Nan Zhang, Atsushi Kubo, Ryan O'Connor, Minwei Mao, Gordon Keller, Jonathan S. Bromberg, Stem Cells, vol. 22: 1205-1217 (2004)
Researchers at Mount Sinai School of Medicine in New York treated mouse stem cells in culture to develop pancreas cells (the cells responsible for producing insulin). Through a series of specific culture treatments, the research team was able to coax mouse stem cells to differentiate into functional pancreas cells that produce insulin.
Dopaminergic Neurons Generated from Monkey Embryonic Stem Cells Function in a Parkinson Primate ModelYasushi Takagi, Jun Takahashi, Hidemoto Saiki, Asuka Morizane, Takuya Hayashi, Yo Kishi, Hitoshi Fukuda, Yo Okamoto, Masaomi Koyanagi, Makoto Ideguchi, Hideki Hayashi, Takayuki Imazato, Hiroshi Kawasaki, Hirofumi Suemori, Shigeki Omachi, Hidehiko Iida, Nobuyuki Itoh, Norio Nakatsuji, Yoshiki Sasai, and Nobuo Hashimoto Journal of Clinical Investigation, January 2005, vol.115: 102-109 (2005)
Scientist from Kyoto University in Japan successfully generated dopaminergic (DA) neurons from monkey stem cells; the loss of DA neurons is associated with the neurodegenerative disorder Parkinson disease. They then transplanted the DA neurons into the brains of several monkeys with Parkinson disease. Analysis of the brain tissue, behavioral studies, and functional imaging revealed that the transplanted cells functioned as DA neurons and diminished the symptoms of Parkinson disease.
Nuclear Reprogramming of Somatic Cells after Fusion with Human Embryonic Stem CellsChad Cowan, Jocelyn Atiendza, Douglas A. Melton, Kevin Eggan, Science, August 26, 2005, vol. 309: 1369-1373 (2005)
Scientists developed a new technique for creating human embryonic stem cells by fusing adult somatic cells with preexisting embryonic stem cell lines. The fusion causes the adult cells to undergo genetic reprogramming, which results in cells that have the developmental characteristics of human embryonic stem cells. This approach could allow for the creation of patient-specific stem cells as an alternative to somatic cell nuclear transfer (SCNT), a cloning method that could be used to produce human stem cells.
Correction of Factor IX Deficiency in Mice by Embryonic Stem Cells Differentiated In VitroJeffrey H. Fair, Bruce A. Cairns, Michael A. Lapaglia, Montserrat Caballero, W. Andrew Pleasant, Seigo Hatada, Hyung-suk Kim, Tong Gui, Larysa Pevny, Anthony A. Meyer, Darrel Stafford, Oliver Smithies, Jeffrey A. Frelinger, PNAS vol. 102: 2958-2963, (2005)
Researchers at the University of North Carolina at Chapel Hill successfully generated mouse embryonic stem cells that may be useful in the treatment of liver-based genetic defects such as hemophilia A and B, a disease characterized by the lack of clotting substance factor IX. Mouse embryonic stem cells were grown in culture for seven days with a special growth factor and allowed to differentiate. The differentiated stem cells were then injected into the liver and shown to reverse a form of hemophilia in mice similar to hemophilia B in humans.
Human Embryonic Stem Cell Lines with Genetic DisordersY. Verlinsky, N. Strelchenko, F. Kikharenko, S. Rechitsky, O. Verlinsky, V. Galat, A. Kuliev, Reproductive BioMedicine Online, January 2005, vol. 10. No 1.2005 105-110.
Privately-funded researchers from the Reproductive Genetics Institute
in Chicago derived twelve embryonic stem cell lines that express seven
different genetic defects: myotonic dystrophy, Duchenne muscular dystrophy,
neurofibromatosis type 1, Fragile X and Marfan syndromes, beta-thalassaemia,
and Fanconi anaemia. The embryos were reportedly donated by couples undergoing
pre-implantation genetic diagnosis at the clinic. These are the first
embryonic stem-cell lines to be derived from embryos with specific genetic
diseases and may become valuable tools for studying the cellular functions
of specific genetic diseases.
Derivation of Multipotent Mesenchymal Precursors from Human Embryonic Stem CellsTiziano Barberi, Lucy M. Willis, Nicholas D. Socci, Lorenz Studer, PLOS Medicine, June 2005. vol 2: 0554-0560 (2005)
Scientists at the Sloan-Kettering Institute in New York successfully cultured mesenchymal cells; the precursor cells for bone, cartilage, fat and muscle development. The group took two lines of undifferentiated human embryonic stem cells and cultured them in a mix of mouse feeder cells. The cells were then treated with a chemical compound mixture that coaxed the cells to differentiate into specialized bone, cartilage, fat, and muscle cells. The research indicates that it is possible to produce tissue-type cells for human transplantation; however, future human clinical treatments would require a non-animal culture material.
Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitor Cell Transplants Remyelinate and Restore Locomotion after Spinal Cord InjuryHans S. Keirstead, Gabriel Nistor, Giovanna Bernal, Minodora Totoiu, Frank Cloutier, Kelly Sharp, and Oswald Steward, Journal of Neuroscience, vol. 25: 4694-4705 (2006)
Scientists in the Reeve-Irvine Research Center at UC Irvine used human embryonic stem cells to create oligodendrocyte progenitor cells. Oligodendrocytes are a type of cell in the central nervous system that surround and insulate axons (the long cell processes through which nerves send their electrical messages). The embryonic stem cells were transplanted into rats suffering from spinal cord injuries at either 7 days or 10 months after injury. The rats treated after 7 days exhibited recovery of motor function while those treated after 10 months did not. The findings point to the potential of using stem cell-derived therapies for treatment of spinal cord damage in humans during the very early stages of the injury.
Derivation of Human Embryonic Stem Cells in Defined ConditionsTenneille E. Ludwig, Mark E. Levenstein, Jeffrey M. Jones, W. Travis Berggren, Erika R. Mitchen, Jennifer L. Frane, Leann Crandall, Christine A. Daigh, Kevin R. Conard, Marian S. Piekarczyk, Rachel A. Llanas, James A. Thomson, Nature Biotechechnology, February 2006, vol. 24: 185-187 (2006)
Scientists working at the WiCell Research Institute, a private laboratory affiliated with the University of Wisconsin-Madison, developed a precisely defined stem cell culture system free of animal cells and used it to derived two new human embryonic stem cell lines. The initial derivation of human embryonic stem cells in 1998 "depended on standard tissue culture technology established in the 1950s." This old technology relies on a culture medium which contains animal products that could harbor viruses or other problematic agents and render the stem cells useless for human therapies. The WiCell Research Institute's new stem cell lines provide an opportunity to develop stem cell therapies with improved clinical applications to humans.
Recovery from Paralysis in Adult Rats Using Embryonic Stem CellsDeshpande D, Kim YS, Martinez T, Carmen J, Dike S, Shats I, Rubin L, Drummond J, Krishnan C, Hoke A, Maragakis N, Shefner J, Rothstein J, Kerr D. "Recovery from Paralysis in Adult Rats Using Embryonic Stem Cells." Annals of Neurology, July 2006, Vol. 60, No. 1, pp. 22-34
For the first time in adult mammals, Johns Hopkins scientists have discovered
how to restore lost nerve function. The research team, led by Douglas
Kerr, M.D., Ph.D., injected mouse embryonic stem cells into the damaged
spinal cords of paralyzed adult rats. The stem cells, stimulated with
nerve growth chemicals, caused 11 of the 15 treated animals to recover
muscle strength, and enabled them to use their previously paralyzed hind
legs. Previous studies have demonstrated the ability of embryonic stem
cells to assist in the repair of motor circuits but this is the first
study whereby embryonic stem cells replaced the damaged nerve connection.
These connections are believed to be crucial to the recovery of the rats.
Within humans, this technique could have therapeutic benefit for those suffering from fatal motor neuron diseases, such as spinal muscular atrophy and amyotrophic lateral sclerosis (ALS). Before clinical testing can occur for these and other diseases, researchers need to develop larger animal models and conduct research using human embryonic stem cells. Dr. Kerr and other members of the Hopkins research team plan to use human embryonic stem cells in pig models to determine the potential effectiveness of the method in humans.
Updated July 13, 2007