| GENTAUR Europe BVBA
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45
Fax 0032 16 50 90 45
GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50
Fax 01 43 25 01 60
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531
Fax 020 8445 9411
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
GENTAUR SRL IVA IT03841300167
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
GENPRICE Inc. invoicing/ accounting:
6017 Snell Ave, Suite 357
San Jose, CA. 96123
Fax 0032 16 50 90 45
Schweiz Züri +41435006251
Ceská republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Magyarország Budapest +3619980547
The process researchers use to generate induced pluripotent stem cells (iPSCs) -- a special type of stem cell that can be made in the lab from any type of adult cell -- is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth.
As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.
"Generating iPSCs depends on the regulation of communication networks within cells," explained Tariq Rana, Ph.D., program director in Sanford-Burnham's Sanford Children's Health Research Center and senior author of the study. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."
According to Tony Hunter, Ph.D., professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, "The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana's exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes." Hunter, a kinase expert, was not involved in this study.
The promise of iPSCs
At the moment, the only treatment option available to many heart failure patients is a heart transplant. Looking for a better alternative, many researchers are coaxing stem cells into new heart muscle. In Alzheimer's disease, researchers are also interested in stem cells, using them to reproduce a person's own malfunctioning brain cells in a dish, where they can be used to test therapeutic drugs. But where do these stem cells come from? Since the advent of iPSC technology, the answer in many cases is the lab. Like their embryonic cousins, iPSCs can be used to generate just about any cell type -- heart, brain, or muscle, to name a few -- that can be used to test new therapies or potentially to replace diseased or damaged tissue.
It sounds simple enough: you start with any type of differentiated cell, such as skin cells, add four molecules that reprogram the cells' genomes, and then try to catch those that successfully revert to unspecialized iPSCs. But the process takes a long time and isn't very efficient -- you can start with thousands of skin cells and end up with just a few iPSCs.
Inhibiting kinases to make more iPSCs
Zhonghan Li, a graduate student in Rana's laboratory, took on the task of finding kinase inhibitors that might speed up the iPSC-generating process. Scientists in the Conrad Prebys Center for Chemical Genomics, Sanford-Burnham's drug discovery facility, provided Li with a collection of more than 240 chemical compounds that inhibit kinases. Li painstakingly added them one-by-one to his cells and waited to see what happened. Several kinase inhibitors produced many more iPSCs than the untreated cells -- in some cases too many iPSCs for the tiny dish housing them. The most potent inhibitors targeted three kinases in particular: AurkA, P38, and IP3K.
Working with the staff in Sanford-Burnham's genomics, bioinformatics, animal modeling, and histology core facilities -- valuable resources and expertise available to all Sanford-Burnham scientists and the scientific community at large -- Rana and Li further confirmed the specificity of their findings and even nailed down the mechanism behind one inhibitor's beneficial actions.
"We found that manipulating the activity of these kinases can substantially increase cellular reprogramming efficiency," Rana said. "But what's more, we've also provided new insights into the molecular mechanism of reprogramming and revealed new functions for these kinases. We hope these findings will encourage further efforts to screen for small molecules that might prove useful in iPSC-based therapies."
Check out the newest antimicrobials and cell biology reagents below.
Ethambutol DiHCl (E005) - anti-tubercular antibiotic, inhibits cell wall synthesis in Mycobacterium species.
Cefmetazole sodium (C052) - broad spectrum, second generation cephalosporin.
Cefotetan disodium (C117) - cephamycin antibiotic, especially effective against anaerobic bacteria.
Thiostrepton, Ultrapure (T042) - cyclic peptide antibiotic, inhibits protein synthesis. Thiostrepton, ultrapure is >98.0% pure.
Cell Biology Reagents
Avermectin B1a, EvoPure® (A063) - Macrocycline lactone used in agricultural and veterinary applications as an insecticide and anti-parasitic agent, respectively.
Omeprazole (O011) - Antacid compound which inhibits enzymes that aid in gastric acid secretion.
Paclitaxel (P045) - Anti-tumor agent active in the G2/M growth phase during mitosis.
Zymosan A (Z001) - Stimulates TLR-2, an immunologic receptor which recognizes surface proteins in bacteria.
Antibodies for :
Arabidopsis thaliana, Chlamydomonas sp. , diatoms, Hordeum vulgare, Nicotiana tabacum, Oryza sativa, Physcomitrella patens, Pisum sativum, Populus sp., Spinacia oleracea, Synechococcus sp., Zea mays. And many more!
For: western blot, immunolocalizations, IP
Speed up Your research with the most comprehensive plant and algal antibody collection from original manufacturer
All antibodies are carefully validated by our own testing laboratory or in collaboration with scientists in the field.
Contact us and we will help you to find the right antibody for your application!
A new approach mimicking the body’s natural defenses could help treat a therapy-resistant breast cancer
Some of these therapy-resistant cancers have a potential molecular target for cancer drugs, a growth-factor receptor called EGFR, but an EGFR-blocking drug has proved ineffective in treating them. In a study published recently in the Proceedings of the National Academy of Sciences, Weizmann Institute researchers propose a potential solution: to simultaneously treat triple-negative breast cancer with two EGFR-blocking antibodies instead of one. In a study in mice, the scientists showed that a certain combination of two antibodies indeed prevented the growth and spread of triple-negative tumors. The research team, led by Prof. Yosef Yarden of the Biological Regulation Department and Prof. Michael Sela of the Immunology Department, included Drs. Daniela Ferraro, Nadège Gaborit, Ruth Maron, Hadas Cohen-Dvashi, Ziv Porat and Fresia Pareja, and Sara Lavi, Dr. Moshit Lindzen and Nir Ben-Chetrit.
Of the different combinations they tried, the scientists found that the approach worked when the two antibodies bound to different parts of the EGFR molecule. The combined action of the antibodies was stronger than would have been expected by simply adding up the separate effects of each. Apparently, the use of the two antibodies created an entirely new anti-cancer mechanism: In addition to blocking the EGFR and recruiting the help of immune cells, the antibodies probably overwhelmed the EGFR by their sheer weight, causing it to collapse inward from the membrane into the tumor cell.
If supported by further studies, the two-antibody approach, in combination with chemotherapy, might in the future be developed into an effective treatment for triple-negative breast cancer.