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Choijamts B.,Fukuoka University | Jimi S.,Fukuoka University | Kondo T.,Ehime University | Kondo T.,Center for Developmental Biology | And 6 more authors.
Stem Cells | Year: 2011

Cancer stem cells (CSCs) that display tumor-initiating properties have recently been identified. CD133, a surface glycoprotein linked to organ-specific stem cells, has been described as a marker of CSCs in different tumor types. We herein identify and characterize CSCs in human uterine carcinosarcoma (malignant mixed Müllerian tumor), which is one of the most aggressive and therapy-resistant gynecological malignancies and is considered to be of mesodermal origin. The CD133 + population was increased in uterine carcinosarcoma, and this population showed biphasic properties in the primary tumor. CD133 + cells predominantly formed spheres in culture and were able to differentiate into mesenchymal lineages. CD133 + cells were more resistant to cisplatin/paclitaxel-induced cytotoxicity in comparison with CD133 - cells. A real-time polymerase chain reaction analysis of the genes implicated in stem cell maintenance revealed that CD133 + cells express significantly higher levels of Oct4, Nanog, Sox2, and Bmi1 than CD133 - cells. Moreover, CD133 + cells showed a high expression level of Pax2 and Wnt4, which are genes essential for Müllerian duct formation. These CD133 +cells form serially transplantable tumors in vivo and the resulting CD133 + tumors replicated the EpCAM, vimentin, and estrogen and progesterone receptor expression of the parent tumor, indicating that CSCs likely differentiated into cells comprising the uterine carcinosarcoma tissue. Moreover, strong CD133 expression in both epithelial and mesenchymal elements in primary tumor demonstrated significant prognostic value. These findings suggest that CD133 + cells have the characteristics of CSCs and Müllerian mesenchymal progenitors. © AlphaMed Press. Source


Caprioli A.,Center for Developmental Biology | Koyano-Nakagawa N.,University of Minnesota | Koyano-Nakagawa N.,Lillehei Heart Institute | Iacovino M.,University of Minnesota | And 6 more authors.
Circulation | Year: 2011

Background-: Recent studies suggest that the hematopoietic and cardiac lineages have close ontogenic origins, and that an early mesodermal cell population has the potential to differentiate into both lineages. Studies also suggest that specification of these lineages is inversely regulated. However, the transcriptional networks that govern the cell fate specification of these progenitors are incompletely defined. Methods and results-: Here, we show that Nkx2-5 regulates the hematopoietic/erythroid fate of the mesoderm precursors early during cardiac morphogenesis. Using transgenic technologies to isolate Nkx2-5 expressing cells, we observed an induction of the erythroid molecular program, including Gata1, in the Nkx2-5-null embryos. We further observed that overexpression of Nkx2-5 with an Nkx2-5-inducible embryonic stem cell system significantly repressed Gata1 gene expression and suppressed the hematopoietic/erythroid potential, but not the endothelial potential, of the embryonic stem cells. This suppression was cell-autonomous, and was partially rescued by overexpressing Gata1. In addition, we demonstrated that Nkx2-5 binds to the Gata1 gene enhancer and represses the transcriptional activity of the Gata1 gene. Conclusions-: Our results demonstrate that the hematopoietic/ erythroid cell fate is suppressed via Nkx2-5 during mesodermal fate determination, and that the Gata1 gene is one of the targets that are suppressed by Nkx2-5. © 2011 American Heart Association, Inc. Source


News Article
Site: http://news.yahoo.com/science/

In a lab in Japan, researchers have grown complex skin tissue, complete with hair follicles and sweat glands, according to a new study. The researchers implanted the tissue into living mice, and found that the tissue formed connections with the animals' nerves and muscle fibers. The findings may one day help researchers create better skin transplants for human patients with severe burns or skin diseases. Prior to the new study, researchers had already developed a more basic type of skin substitute that had been used successfully in human patients, said Takashi Tsuji, a team leader at RIKEN Center for Developmental Biology in Japan. But that skin had only one or two layers of tissue, and lacked features such as hair follicles and the glands that secrete sweat and oil called sebum, he said. In the new research, the scientists generated skin that had not only those features but also all three layers of tissue that normal skin has. [5 Ways Skin Can Signal Health Problems] The work began with cells collected from mouse gums. The researchers used chemicals to transform these cells into cells that were similar to stem cells. Then, the researchers used these cells to generate three-layered, fully functioning skin tissue in lab dishes. Then, they transplanted this tissue, complete with hair follicles and glands that produce sebum, into mice. The researchers found that the tissue made normal connections with surrounding nerves and muscle tissues in the mice, and those connections allowed the tissue to function normally. The mice's immune systems did not reject the transplanted tissues. Moreover, 14 days after the tissue had been transplanted, the researchers noticed that hair had sprouted from the bioengineered hair follicles and started to grow. [Top 3 Techniques for Creating Organs in the Lab] "Our present outcomes indicate a proof of concept of regenerative therapy of [a] fully functional and integrated skin organ system that will have a potential for the application of the future clinical treatment," Tsuji told Live Science. However, the researchers noted that, to generate human tissue for use in people, they would have to start with human cells, and would still have to figure out how to grow skin tissue from those cells, the researchers said. Besides its potential application in human patients, the newly developed skin tissue also could be used as an alternative to testing cosmetics on animals, the researchers said. The researchers are currently trying to generate other organs that are associated with skin tissue, such as teeth and salivary glands, Tsuji said. The new study was published today (April 1) in the journal Science Advances. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


News Article | December 21, 2015
Site: http://www.techtimes.com/rss/sections/science.xml

It looks like scientists have found a way for humans to possibly regenerate their teeth long after they grow out of believing in the Tooth Fairy. A new study has revealed that it might be possible to grow multiple teeth from a sole root — meaning that it might be possible for humans to regrow fully functional teeth. Published on Dec. 17 in the scientific journal Nature, scientists at Tokyo Medical and Dental University and the Riken Center for Developmental Biology detailed their process and findings, which stated that their "tooth regenerative technology [is] based on split tooth germs and the re-regionalization of the tooth-forming field by artificial mechanical force." In layman's terms, this means that their conclusion relies on manipulating the function of a "tooth germ" (or a tiny plumule located in the root that transmits info via protein signals, which clue in cells to group and form into teeth), paired with a little human intervention. For their experiment, the researchers extracted these tooth germs from mice and split them using a simple nylon thread to control exactly how the teeth regenerated. The scientists were able to correctly regrow these split germs into a collection of healthy teeth "through the re-regionalization of the tooth-forming field, which is regulated by reaction-diffusion waves in response to mechanical force." Another catch? To be fully functional, a given regenerated tooth had to be able to develop a tooth germ all on its own — which they were able to do if the initial germ was vivisected at 14.5 days of development. While the team's successful results have only been derived from animal testing, their findings are still a hopeful step for humans, in an effort that might revolutionize the dental industry and medical field as we know it.


News Article
Site: http://blogs.nature.com/news

Stem cells that were claimed to be created simply by exposing ordinary cells to stress were probably derived from embryonic stem cells, according to the latest investigation into an ongoing scientific scandal. How that contamination occurred, however, remains an open question. The investigation was instigated by RIKEN, the Japanese research institution where the original claims were made, and carried out by a committee composed of seven outsiders. The committee analyzed DNA samples and laboratory records from two teams behind the original papers describing STAP (‘stimulus-triggered acquisition of pluripotency’) cells.  Those papers — published in Nature but later retracted  — were once heralded as describing a shortcut to producing stem cells: rather than expressing specific genes or carefully transplanting a nucleus from one cell to another, researchers could, it seemed, create stem cells by exposing them to stress, including bathing the cells in acid. The latest investigation suggests that the STAP findings were merely the result of contamination by embryonic stem cells. Investigators found signs of three separate embryonic stem cell lines. They noted that it is difficult to imagine how contamination by three distinct lines could be accidental, but that they could also not be certain that it was intentional. “We cannot, therefore, conclude that there was research misconduct in this instance,” the committee wrote. It did, however, find evidence that lead investigator Haruko Obokata, formerly of the RIKEN Center for Developmental Biology in Kobe, had fabricated data for two figures in the original STAP publications. The committee’s report, released on 26 December, is the latest in a series of damning revelations about the STAP cells originally described in two Nature papers in January 2014. The approach quickly came under scrutiny as other researchers failed to reproduce its results, and as suspicions grew that images in the original papers had been manipulated. In March, another RIKEN investigation found Obokata guilty of scientific misconduct; in July, the STAP papers were retracted  and in August another co-author, Yoshiki Sasai, took his own life. Earlier this month, Obokata resigned her position at RIKEN.

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