ScienceWeek

SCIENCEWEEK

May 11, 2007

Vol. 11 - Number 18

STEM CELLS

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This vain presumption of understanding everything can have no other basis than never understanding anything. For anyone who had experienced just once the perfect understanding of one single thing, and had truly tasted how knowledge is accomplished, would recognize that infinity of other truths of which he understands nothing.

-- Galileo Galilei

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Contents (full text below):

1. On Stem Cells

2. Trends in Stem Cell Proteomics

3. The Significant Cardiomyogenic Potential of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Vitro

4. Directed Differentiation and Transplantation of Human Embryonic Stem Cell Derived Motoneurons

5. Links to Further Information

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1.

On Stem Cells

http://stemcells.nih.gov/info/basics/basics1.asp

Stem cells have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that renew themselves for long periods through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas.

Scientists primarily work with two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells, which have different functions and characteristics that will be explained in this document. Scientists discovered ways to obtain or derive stem cells from early mouse embryos more than 20 years ago. Many years of detailed study of the biology of mouse stem cells led to the discovery, in 1998, of how to isolate stem cells from human embryos and grow the cells in the laboratory. These are called human embryonic stem cells. The embryos used in these studies were created for infertility purposes through in vitro fertilization procedures and when they were no longer needed for that purpose, they were donated for research with the informed consent of the donor.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, stem cells in developing tissues give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

It has been hypothesized by scientists that stem cells may, at some point in the future, become the basis for treating diseases such as Parkinson's disease, diabetes, and heart disease.

Scientists want to study stem cells in the laboratory so they can learn about their essential properties and what makes them different from specialized cell types. As scientists learn more about stem cells, it may become possible to use the cells not just in cell-based therapies, but also for screening new drugs and toxins and understanding birth defects. However, as mentioned above, human embryonic stem cells have only been studied since 1998. Therefore, in order to develop such treatments scientists are intensively studying the fundamental properties of stem cells, which include:

1. determining precisely how stem cells remain unspecialized and self renewing for many years; and 2. identifying the signals that cause stem cells to become specialized cells.

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Stem Cells for the Future Treatment of Parkinson's Disease

Parkinson's disease (PD) is a very common neurodegenerative disorder that affects more than 2% of the population over 65 years of age. PD is caused by a progressive degeneration and loss of dopamine (DA)-producing neurons, which leads to tremor, rigidity, and hypokinesia (abnormally decreased mobility). It is thought that PD may be the first disease to be amenable to treatment using stem cell transplantation. Factors that support this notion include the knowledge of the specific cell type (DA neurons) needed to relieve the symptoms of the disease. In addition, several laboratories have been successful in developing methods to induce embryonic stem cells to differentiate into cells with many of the functions of DA neurons.

In a recent study, scientists directed mouse embryonic stem cells to differentiate into DA neurons by introducing the gene Nurr1. When transplanted into the brains of a rat model of PD, these stem cell-derived DA neurons reinnervated the brains of the rat Parkinson model, released dopamine and improved motor function.

Regarding human stem cell therapy, scientists are developing a number of strategies for producing dopamine neurons from human stem cells in the laboratory for transplantation into humans with Parkinson's disease. The successful generation of an unlimited supply of dopamine neurons could make neurotransplantation widely available for Parkinson's patients at some point in the future.

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2.

Trends in Stem Cell Proteomics

Hossein Baharvand, Ali Fathi, Dennis van Hoof, Ghasem Hosseini Salekdeh

Stem Cells Express, first published online May 11, 2007; doi:10.1634/stemcells.2007-0107

Gene expression analyses of stem cells (SCs) will help to uncover or further define signaling pathways and molecular mechanisms involved in the maintenance of self-renewal, pluripotency, and/or multipotency. In recent years, proteomic approaches have produced a wealth of data identifying proteins and mechanisms involved in SC proliferation and differentiation. Although many proteomics techniques have been developed and improved in peptide and protein separation as well as mass spectrometry, several important issues including sample heterogeneity, post-translational modifications, protein-protein interaction, and high throughput quantification of hydrophobic and low abundant proteins still remain to be addressed and require further technical optimization. The following review summarizes the methodologies used and the information gathered with proteome analyses of SCs, and discusses biological and technical challenges for proteomic study of SCs.

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3.

The Significant Cardiomyogenic Potential of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Vitro

Nobuhiro Nishiyama, Shunichiro Miyoshi, Naoko Hida Miss, Taro Uyama, Kazuma Okamoto, Yukinori Ikegami, Kenji Miyado, Kaoru Segawa, Masanori Terai, Michiie Sakamoto, Satoshi Ogawa, Akihiro Umezawa

Stem Cells Express, first published online May 10, 2007; doi:10.1634/stemcells.2006-0662

We tested the cardiomyogenic (CM) potential of the human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). Both the number and function of stem cells may be depressed in senile patients with severe coronary risk factors. Therefore, stem cells obtained from such patients may not function well. For this reason, UCBMSCs are potentially a new cell source for stem cell-based therapy, since such cells can be obtained from younger populations and are being routinely utilized for clinical patients.

Methods and Results: The human UCBMSCs (5x103/cm2) were co-cultured with fetal murine cardiomyocytes (CM:1x105/cm2). On day 5 of co-cultivation, about half of the GFP-labeled UCBMSCs contracted rhythmically and synchronously, suggesting the presence of electrical communication between the UCBMSCs. The fractional shortening of the contracted UCBMSCs was 6.5 ± 0.7 % (n=20). The UCBMSC-derived cardiomyocytes stained positive for cardiac troponin-I (clear striation +) and connexin 43 (diffuse dot-like staining at the margin of the cell) by the immunocytochemical method. Cardiac troponin-I positive cardiomyocytes accounted for 45 ± 3 % of GFP-labeled UCBMSCs. The cardiomyocyte-specific long action potential duration (186 ± 12 msec) was recorded with a glass microelectrode from the GFP-labeled UCBMSCs. CM was observed in UCBMSCs, which were co-cultivated in the same dish with mouse cardiomyocytes separated by a collagen membrane. Cell fusion, therefore, was not a major cause of CM in the UCBMSCs.

Conclusions: About half of the human UCBMSCs were successfully transdifferentiated into cardiomyocytes in vitro. UCBMSCs can be a promising cellular source for cardiac stem cell-based therapy.

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4.

Directed Differentiation And Transplantation of Human Embryonic Stem Cell Derived Motoneurons

Hyojin Lee, George Al Shamy, Yechiel Elkabetz, Claude M. Schoefield, Neil L. Harrsion, Georgia Panagiotakos, Nicholas D. Socci, Viviane Tabar, Lorenz Studer

Stem Cells Express, first published online May 3, 2007; doi:10.1634/stemcells.2007-0097

Motoneurons represent a specialized class of neurons essential for the control of body movement. Motoneuron loss is the cause of a wide range of neurological disorders including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Embryonic stem cells are promising cell source for the study and potential treatment of motoneuron diseases.

Here we present a novel in vitro protocol of the directed differentiation of human embryonic stem cells (hESCs) into engraftable motoneurons. Neural induction of hESCs was induced on MS5 stromal feeders resulting in the formation of neural rosettes. In response to sonic hedgehog (SHH) and retinoic acid (RA) neural rosettes were efficiently directed into spinal motoneurons with appropriate in vitro morphological, physiological and biochemical properties. Global gene expression analysis was used as an unbiased measure to confirm motoneuron identity and type. Transplantation of motoneuron progeny into the developing chick embryo resulted in robust engraftment, maintenance of motoneuron phenotype and long-distance axonal projections into peripheral host tissues. Transplantation into the adult rat spinal cord yielded neural grafts comprising large number of human motoneurons with outgrowth of choline acetyltransferase positive fibers. These data provide evidence for in vivo survival of hESC-derived motoneurons, a key requirement in the development of hESC based cell therapy in motoneuron disease.

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5.

Stem Cells in the Spotlight Explore the biology of stem cells, their potential uses in medicine and some of the challenges facing stem cell research. http://gslc.genetics.utah.edu/units/stemcells

TIME.com - Stem Cells The debate over stem cell research has raised many questions across the nation. Time.com examines the issues and how it will affect you. www.time.com/time/2001/stemcells/

NOVA | scienceNOW | Stem Cells | PBS Explore the arguments for and against cloning for stem cell research in an interactive poll, see microphotographs of the cloning process, ask Dr. Leonard ... www.pbs.org/wgbh/nova/sciencenow/3209/04.html

Stem Cells A free collection of articles about stem cells published in The New York Times. http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/stemcells/index.html

Embryonic Stem Cell Research at UW-Madison News and background information detailing embryonic stem cell research at the University of Wisconsin-Madison, the site where professor James Thomson in ... www.news.wisc.edu/packages/stemcells/

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