Newsletter: 4 stem cell patents issued last week

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4 stem cell patents issued last week

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Dear manoj kumar valluru,

Last week 4 patents of relevance to the area of stem cells were issued.

1. # 7,323,165 (Patent Spotlight), teaches how to make insulin in vivo by transfection with ngn3 an dother transcription factors.

2. # 7,323,190 discloses a new fibrous matrix for cell delivery.

3. # 7,323,337 covers viral transfection of ES cells using SIV.

4. # 7,323,445 blocks the use of osteochondral grafts with specific BMPs.

In The News

Breast cancer FGF-2 and VEGF calls in mesenchymal stem cells

Tuesday January 29th, 2008 @ 03:01:42 EST

Augusta, Georgia -

It is believed by many that tissue resident stem cells subsequent to accumulating DNA damage lose proliferative controls and transform into tumors. For example, there is a classical study in which mice were infected with h.pylori and gastric cancer was allowed to develop. Strikingly, the gastric cancer was derived from bone marrow stem cells which had migrated to heal the damaged stomach tissue and subsequently transformed into cancer cells _(Houghton et al Gastric cancer originating from bone marrow-derived cells.Science. 2004 Nov 26;306:1568-71)_

One interesting finding is that not only do cancer cells seem to attract various types of stem cells, but that in some situation administration of healthy stem cells can inhibit the cancer growth Evan Synder from San Diego has actually been proposing these types of approaches for targeting brain tumors. For example, in his issued US patent 7,186,409 he teaches that neural stem cells can be used as vectors to carry toxic payloads to brain tumors.

A very important question is how do tumor cells call in stem cells? Well off the top of one's head, one would imaging that since stem cells are usually attracted by injury signals similar to the ones that call in bone marrow stem cells to home into injured myocardium after a heart attack and since tumors are considered "wounds that never heal", it may be possible that signals such as SDF-1 may be chemoattracting stem cells to tumor cells.

In a recent study _(Ritter et al. Breast Cancer Cell-Derived Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor Are Chemoattractants for Bone Marrow Stromal Stem Cells. Ann Surg. 2008 Feb;247:310-314)_ the interaction between tumors and stem cells was examined. Researchers used in vitro breast cancer cell lines to determine that these cells have a chemoattracting property to bone marrow derived mesenchymal stem cells when placed in Boyden chambers.

Chemoattractants of relevance were VEGF and FGF-2. Particularly mesenchymal stem cells expressed receptors for these cytokines, and the tumor cells made these cytokines. The cytokines were found in plasma of cancer patients at high enough concentrations to induce migration of mesenchymal stem cells. Additionally, migration could be inhibited in vitro by blockade of VEGF or FGF-2.

These data provide some clues as to the molecular interaction between tumor cells and mesenchymal stem cells. Since VEGF is clinically inhibited by the anticancer drug Avastin, one wonders whether this affects the interaction of the mesenchymal stem cell with tumor cells.

An additional point of interest is whether the FGF-2 produced by the tumor has other properties besides stimulation of mesenchymal stem cell migration. For example, it is known that FGF-2 increases endothelial health So one question would be, "are the flow mediated vasodilation responses better in cancer patients?"

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This Week's Patent Spotlight

Production of pancreatic islet cells and delivery of insulin

Patent Number: 7,323,165

Assignee | Inventor

Numerous approaches have been patented on the treatment of diabetes through regeneration. These range from bone marrow stem cell modification and administration, to generation of islets from embryonic stem cells to creation of differentiated proliferating islet cell lines

The current patent, belonging to the same family as 6,967,019 teaches methods of producing insulin and of delivering insulin to patients in need of. The methods actually involve stimulation or upregulation of insulin production through inducing expression of a neuroendocrine class B basic helix-loop-helix (bHLH) transcription factor. Expression of these transcription factors is covered in the lumen or duct of a pancreas, as well as the liver and gut.

What are these transcription factors? The claims cover neurogenin1, neurogenin2, NeuroD1/BETA2, neuroD2, math2, NeuroD4/Math3math1/ATOH1, mash1/ASCL1/ASH1, or mash2.

If we look on pubmed, one interesting paper _(Ross et al. Basic helix-loop-helix factors in cortical development. Neuron. 2003 Jul 3;39:13-25)_ tells us that progenitor cells of the neocortex generate new neurons by upregulating activity of bHLH factors (Mash1, Neurogenin1, and Neurogenin2) and a decrease in the activity of Hes and Id factors. The paper provides a general description of what the bHLH transcription factors are. It states that these are a family of 125 member, which are classified as bHLH based on the chemical motif that allows their binding to DNA and also dimerization.

In the specification, it states that the “class B” of the bHLH genes are usually expressed during islet development. Accordingly, if one induces expression of these genes ectopically, the inventors demonstrate one can recapitulate development and start the production of insulin generating cells again. Of particular interest, the patent mentions that the Ngn3 transcription factor is not only involved in endocrine differentiation, but that it controls other islet-specific factors such as Pax4 and Nkx2.2. Interestingly there is a patent issued on the use of Pax4 to determine islet differentiation

The inventor, Dr German, has published numerous papers demonstrating the importance of Ngn3 in pancreatic development, as well as observations that certain types of diabetics have mutations in the ngn3 gene.

The patent has some nice examples supporting the claims, for example a streptozotocin-induced diabetes model having restoration of glycemic control after in vivo viral delivery of ngn3.

Since others have transfected similar, well at least philosophically, similar transcription factors, such as pdx-1 into stem cells to enhance ability to make insulin, maybe this is an approach that will be tried with this technology.

Another interesting angle of research could involve identification of small molecules that upregulate expression of ngn3. Numerous stem cell activities have been modulated pharmacologically, for example, Velcade stimulation of bone formation the activation of hematopoietic stem cells by valproic acid and the use of erythropoietin to stimulate neurogenesis An approach would be to look at DNA arrays and see which drugs that are already on the market may impact ngn3 and then see if the activities may be amplifed by other drugs or approaches.

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RECENTLY ADDED PATENTS

Methods and compositions for healing and repair of articular cartilage

Patent Number: 7,323,445 | Assignee | Inventor | Ask a question OR leave your comments

Gene transfer into primate embryonic stem cells using VSV-G pseudotyped simian immunodeficiency virus vectors

Patent Number: 7,323,337 | Assignee | Inventor | Ask a question OR leave your comments

Cell delivery system comprising a fibrous matrix and cells

Patent Number: 7,323,190 | Assignee | Inventor | Ask a question OR leave your comments

Production of pancreatic islet cells and delivery of insulin

Patent Number: 7,323,165 | Assignee | Inventor | Ask a question OR leave your comments

Unactivated ungulate oocytes to produce a cloned ungulate by nuclear transfer

Patent Number: 7,321,076 | Assignee | Inventor | Ask a question OR leave your comments

Serial nuclear transfer of ungulate embryos

Patent Number: 7,321,075 | Assignee | Inventor | Ask a question OR leave your comments

Ependymal neural stem cells and method for their isolation

Patent Number: 7,320,872 | Assignee | Inventor | Ask a question OR leave your comments

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Patent Number: 7,319,035 | Assignee | Inventor | Ask a question OR leave your comments

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Patent Number: 7,316,822 | Assignee | Inventor | Ask a question OR leave your comments

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Keyword News: [stem cell]

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UTMB gets grant for stem cell research Galveston County Daily News Fri, 01 Feb 2008 9:59 PM PST GALVESTON — A $500,000 grant from the Cullen Foundation will support neurological stem cell research at the University of Texas Medical Branch by funding the purchase of an advanced microscope and supporting a postdoctoral fellow who assists in the studies to optimize stem cell therapy. Carbohydrate Regulates Stem Cell Potency Science Daily Fri, 01 Feb 2008 11:17 AM PST A carbohydrate molecule that coats certain proteins on the cell surface, is critical for the proper proliferation and potency of embryonic stem cells, researchers report. Stem cells' tremendous therapeutic potential arises from their ability to continually self-renew and turn into any adult cell type. Researchers have long been trying to uncover the basis of these abilities, but while several ... Stem cell research company clones human embryo News Democrat & Leader Fri, 01 Feb 2008 6:49 AM PST Stemagen, a privately held embryonic stem cell research company, announced recently it has become the first in the world to create, and meticulously document, a cloned human embryo using somatic cell nuclear transfer (SCNT). Stem Cell Therapy Studies For Stroke, Cerebral Palsy Prepare For Clinical Trials BioresearchOnline Fri, 01 Feb 2008 6:56 AM PST Finding answers about optimal dosage and timing for stem cell therapy in adults with strokes and newborns with ischemic injuries is a goal of two new federally funded studies First Patients Treated In Cytori's Stem & Regenerative Cell Heart Attack Study Medical News Today Fri, 01 Feb 2008 4:16 AM PST Cytori Therapeutics (NASDAQ:CYTX) enrolled the first two patients in a clinical trial using adipose-derived stem and regenerative cells in the treatment of heart attack. In this trial, patients' cells are made available using Cytori's Celution™ System, a real-time cell processing device. Sales of Stem Cell Products Expected to Reach $87 Million in 2008, Leading Medical Industry Analyst Says PR Newswire via Yahoo! Finance Fri, 01 Feb 2008 5:30 AM PST Stem cell product sales in the United States totaled $36 million in 2007, a 119 percent increase from the previous year, and are expected to reach $87 million, a 144 percent increase, in 2008, according to Robin R. Scientists claim victory in blocking stem-cell law after letter in Times Times Online Fri, 01 Feb 2008 3:12 PM PST The letter, published last week, expressed alarm that the Human Fertilisation and Embryology Bill would delay potentially life-saving research by requiring all tissue used to create cloned embryonic stem cells to have the explicit consent of its donor. Cell's phase 2 study shows promising results PharmaBiz Fri, 01 Feb 2008 2:46 AM PST The results of a phase II clinical study by Cell Therapeutics, Inc. (CTI) showed that the addition of radioimmunotherapy (RIT) to high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) produced a high rate of progression-free survival at two years without a significant increase in the toxicity of the HDC regimen underscoring the potential role for RIT in ASCT. The ... Controversial stem cell treatment draws Australians to Indian clinic The Age Fri, 01 Feb 2008 7:13 AM PST Critics are sceptical, but two women say doctors in Delhi have changed their lives. Pope says some science 'shatters' human dignity Gulf Times Fri, 01 Feb 2008 9:59 PM PST VATICAN CITY: Pope Benedict XVI said on Thursday that embryonic stem cell research, artificial insemination and the prospect of human cloning had "shattered" human dignity.

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HSCI Research Newsletter

Harvard Stem Cell Institute Research Newsletter   RESEARCH COMMENTARY SPOTLIGHT ARTICLE REVIEW and COMMENTARY ARTICLES SCIENTIFIC PAPERS cancer cardiovascular system developmental biology diabetes imaging immunology nervous system renal system technology This HSCI Research Update synthesizes the scientific work published by HSCI Principal Faculty each month. To continue receiving this newsletter, please register as an HSCI Affiliate or Friend by clicking here. If you are having problems viewing this newletter, click here to view it in your web browser. Research Commentary: Stem cell imaging; a vital player in the drive toward therapeutics Spotlight Article: Reprogramming of human somatic cells to pluripotency with defined factors   Research Commentary Stem cell imaging; a vital player in the drive toward therapeutics by Lisa Girard, PhD HSCI Science Editor Progress in stem cell tracking and imaging is critical to the advancement of stem cell-based therapeutics. Reliable in vivo imaging techniques contribute to the potential for stem cell-based gene therapy treatments by identifying and isolating stem cell pools and following stem cell engraftment. Demonstrating the safety of stem cell-based therapeutics is an important hurdle in the path to FDA approval. Tracking transplanted cells and determining where they go and how long they remain in their intended location are critical parameters for understanding the safety of a procedure. Innovative stem cell–based gene therapy and imaging techniques have recently been successfully coupled to deliver anti-tumor therapeutics. Glioblastomas are the most common form of malignant brain tumor and they carry an unfortunate prognosis, with most patients surviving for about two years after diagnosis. New opportunities for stem-cell based treatments for glioblastomas emerged when it was found that transplanted neural precursor cells (NPCs) could migrate and integrate themselves within the central nervous system. Researchers working with Xandra Breakefield of Harvard's Massachusetts General Hospital, including HSCI's Ralph Weissleder (1), engineered NPCs with a type of tumor necrosis factor-related apoptosis-inducing ligand known as S-TRAIL, which can specifically induce cell death in tumor cells when the engineered NPCs are implanted into the head of mice. Researchers were able to visualize this process by including luminescent and bioluminescence transgenes in the NPCs for use in dual bioluminescence imaging. Using this imaging technique, researchers could observe the NPCs migrating to the site and exerting their cell death-inducing properties. 2006 HSCI Seed Grant recipient Rona Carroll and her group at Harvard's Brigham and Women's Hospital also describe tracking methods integral to the success of their research. Carroll and colleagues investigated whether the NPCs could serve as effective anti-tumor drug delivery modules for medulloblastoma, an often-incurable pediatric brain tumor (2). For studies in mice, NPCs were labeled with chloromethylbenzamido-DiI (CM-DiI). CM-DiI is a non-diffusible probe that has been found to be useful for tracking cells for at least two and a half months. The group tested the therapeutic potential of their system using the CD enzyme/5-FC system. CD is a bacterial enzyme that converts the nontoxic 5-FC to the cytotoxic drug 5-FU (5-fluorocytosine to 5-fluorouracil), which disrupts DNA synthesis in proliferating cells by acting as a nucleotide analog. Tumor cells transfected with the E. coli CD gene become susceptible to 5-FU toxicity. This system also has a "bystander effect" that causes the death of tumor cells adjacent to those modified with CD. The CD gene is an example of a "suicide gene" that can not only destroy tumor cells, but can also destroy itself if it starts dividing - a useful feature since tumor formation from transplanted stem cells can be a significant issue. The imaging approaches used in these instances enabled the researchers to gauge whether their anti-tumor methods were working as intended, facilitating progress in the cell-based drug delivery arena. These types of approaches that specifically target tumor cells contribute to the growing trend in therapeutics from systemic to localized delivery, reducing side effects caused by widespread cellular toxicity. Neri et al. (3) from the Stem Cell Research Institute in Italy describe another approach to imaging NPCs. They tracked human NPCs using magnetic resonance (MR) tracking of superparamagnetic iron oxide (SPIRO)-labeled cells. In this method, cells are magnetically labeled using the SPIRO particles, making them traceable by MRI. Studies in mice found that cells could be tracked for up to a month using these methods. This technique has also been used in human mesenchymal and hematopoietic stem cells and is an example of the type of sensitive, non-invasive approach that could be useful for monitoring cell therapy approaches allowing researchers to track transplanted cells in longitudinal studies. Another approach that is being explored with growing interest for non-invasive in vivo imaging is the use of quantum dots. Quantum dots are fluorescent probes that are excited by one wavelength and emit light at different wavelengths, making them ideal for complex imaging. They are also very bright and resistant to photobleaching, important features for probes used in the longitudinal tracking of small numbers of cells. Fluorescent probes that have been used previously are limited in the number of colors they can emit and may emit an overly broad spectrum, making them difficult to use for complex imaging. The brightness of quantum dots is a positive feature for stem cell imaging because its signal is bright enough that it may be less likely to diffuse within tissue. A recent study by Lin et al. (4) at Stanford used quantum dots to label mouse embryonic stem cells. The authors show that the probes do not affect the stem cell's viability, proliferation, or differentiation, making them potentially useful probes. Issues including improving cell retention of the probes must be resolved, however, before quantum dots are optimal probes for longitudinal tracking of stem cell transplants. As we move toward more viable stem cell-based therapeutics, we will see a tight coupling between advances in stem cell biology and advances in imaging that biology. Developments in the areas of long lasting, MR-traceable, and non-diffusible imaging probes are enabling researchers to extend longitudinal studies. This will facilitate the development of new stem cell based therapeutics as cell tracking becomes easier, as well as speed their path from bench to bedside as safety and efficacy can be demonstrated more quickly and directly. References Cowan, C.A., Atienza, J., Melton, D.A., Eggan, K. (2005). Science 309, 1369-73. Okita, K., Ichisaka, T., Yamanaka, S. (2007) Nature 448, 313-7. Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R Science. 2007 Dec 6 [Epub ahead of print] Hyun, I., Hochedlinger, K., Jaenisch, R., Yamanaka, S. (2007) Cell Stem Cell 1, 367-368. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R., Plath, K., Hochedlinger, K. (2007) Cell Stem Cell 1, 55-70. Okita, K., Ichisaka, T., Yamanaka, S. (2007) Nature 448, 313-7. Takahashi, K., and Yamanaka, S. (2006). Cell 126, 663-676. Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. (2007) Nature 448, 318-24.   Spotlight Article Reprogramming of human somatic cells to pluripotency with defined factors Researchers at the Harvard Stem Cell Institute and Childrens Hospital Boston have converted skin cells from an adult into cells that look and act like embryonic stem cells. The resulting cell lines, called induced pluripotent stem cells (iPS), can potentially form any cell type in the body. iPS cells allow a new way for scientists to model human diseases and may one day provide raw material for cell therapies to reverse leukemia, diabetes, Parkinson's disease, and paralysis, among other devastating conditions. The study, led by first-author In Hyun Park, PhD, is similar to reports from laboratories in Japan and the University of Wisconsin that gained worldwide attention in November. However, this study is the first to use tissue from a volunteer research subject rather than cells purchased commercially. "Ours is the only group to go from skin biopsy to cell line," says George Q. Daley, MD, PhD, HSCI Principal Faculty and Executive Committee Member, and the study's senior author. "We developed a strategy that integrates tissue procurement, culturing, and reprogramming the cells. We're now ready to apply this method to cells from patients with a variety of diseases." Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2007 Dec 23. Read Abstract.    Review and Commentary Articles Ptaszek LM, Cowan CA. New Tools for Genome Modification in Human Embryonic Stem Cells. Cell Stem Cell. 2007 Dec 13:1(6):600-602. Read Abstract. Scadden DT. The weight of cell identity. J Clin Invest. 2007 Dec;117(12):3653-5. Read Abstract.  Cancer Gee MS, Upadhyay R, Bergquist H, Weissleder R, Josephson L, Mahmood U. Multiparameter noninvasive assessment of treatment susceptibility, drug target inhibition and tumor response guides cancer treatment. Int J Cancer. 2007 Dec 1;121(11):2492-500. Read Abstract. Li Z, Tognon CE, Godinho FJ, Yasaitis L, Hock H, Herschkowitz JI, Lannon CL, Cho E, Kim SJ, Bronson RT, Perou CM, Sorensen PH, Orkin SH. ETV6-NTRK3 Fusion Oncogene Initiates Breast Cancer from Committed Mammary Progenitors via Activation of AP1 Complex. Cancer Cell. 2007 Dec;12(6):542-58. Read Abstract. Fröhling S, Scholl C, Levine RL, Loriaux M, Boggon TJ, Bernard OA, Berger R, Döhner H, Döhner K, Ebert BL, Teckie S, Golub TR, Jiang J, Schittenhelm MM, Lee BH, Griffin JD, Stone RM, Heinrich MC, Deininger MW, Druker BJ, Gilliland DG. Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles. Cancer Cell. 2007 Dec;12(6):501-13. Read Abstract. Swanson KD, Winter JM, Reis M, Bentires-Alj M, Greulich H, Grewal R, Hruban RH, Yeo CJ, Yassin Y, Iartchouk O, Montgomery K, Whitman SP, Caligiuri MA, Loh ML, Gilliland DG, Look AT, Kucherlapati R, Kern SE, Meyerson M, Neel BG. SOS1 mutations are rare in human malignancies: Implications for Noonan syndrome patients. Genes Chromosomes Cancer. 2007 Dec 6;47(3):253-259. Read Abstract. Gounaris E, Erdman SE, Restaino C, Gurish MF, Friend DS, Gounari F, Lee DM, Zhang G, Glickman JN, Shin K, Rao VP, Poutahidis T, Weissleder R, McNagny KM, Khazaie K. Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci USA. 2007 Dec 11;104(50):19977-82. Read Abstract. Del Gaizo Moore V, Schlis KD, Sallan SE, Armstrong SA, Letai A. BCL-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood. 2007 Dec 4. Read Abstract.  Cardiovascular System Yamamoto R, Akazawa H, Ito K, Toko H, Sano M, Yasuda N, Qin Y, Kudo Y, Sugaya T, Chien KR, Komuro I. Angiotensin II type 1a receptor signals are involved in the progression of heart failure in MLP-deficient mice. Circ J. 2007 Dec;71(12):1958-64. Read Abstract.  Developmental Biology Rompani SB, Cepko CL. Retinal progenitor cells can produce restricted subsets of horizontal cells. Proc Natl Acad Sci USA. 2007 Dec 27. Read Abstract. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2007 Dec 23. Read Abstract.  Diabetes Marselli L, Thorne J, Ahn YB, Omer A, Sgroi DC, Libermann T, Otu HH, Sharma A, Bonner-Weir S, Weir GC. Gene expression of purified beta cell tissue obtained from human pancreas with laser capture microdissection. J Clin Endocrinol Metab. 2007 Dec 11. Read Abstract. Papas KK, Pisania A, Wu H, Weir GC, Colton CK. A stirred microchamber for oxygen consumption rate measurements with pancreatic islets. Biotechnol Bioeng. 2007 Dec 1;98(5):1071-82. Read Abstract.  Imaging Korngold EC, Jaffer FA, Weissleder R, Sosnovik DE. Noninvasive imaging of apoptosis in cardiovascular disease. Heart Fail Rev. 2007 Dec 12. Read Abstract. Harisinghani M, Ross RW, Guimaraes AR, Weissleder R. Utility of a new bolus-injectable nanoparticle for clinical cancer staging. Neoplasia. 2007 Dec;9(12):1160-5. Read Abstract. Nahrendorf M, Zhang H, Hembrador S, Panizzi P, Sosnovik DE, Aikawa E, Libby P, Swirski FK, Weissleder R. Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis. Circulation. 2007 Dec 24. Read Abstract. Bouffard J, Kim Y, Swager TM, Weissleder R, Hilderbrand SA. A highly selective fluorescent probe for thiol bioimaging. Org Lett. 2008 Jan 3;10(1):37-40. Epub 2007 Dec 7. Read Abstract.  Immunology Noor S, Goldfine H, Tucker DE, Suram S, Lenz LL, Akira S, Uematsu S, Girotti M, Bonventre JV, Breuel K, Williams DL, Leslie CC. Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2. J Biol Chem. 2007 Dec 14. Read Abstract.  Nervous System Gao X, Arlotta P, Macklis JD, Chen J. Conditional knock-out of beta-catenin in postnatal-born dentate gyrus granule neurons results in dendritic malformation. J Neurosci. 2007 Dec 26;27(52):14317-25. Read Abstract. Chang BS, Katzir T, Liu T, Corriveau K, Barzillai M, Apse KA, Bodell A, Hackney D, Alsop D, Wong S, Walsh CA. A structural basis for reading fluency: white matter defects in a genetic brain malformation. Neurology. 2007 Dec 4;69(23):2146-54. Read Abstract. Rajab A, Manzini MC, Mochida GH, Walsh CA, Ross ME. A novel form of lethal microcephaly with simplified gyral pattern and brain stem hypoplasia. Am J Med Genet A. 2007 Dec 1;143(23):2761-7. Read Abstract.  Renal System van Timmeren MM, Vaidya VS, van Ree RM, Oterdoom LH, de Vries AP, Gans RO, van Goor H, Stegeman CA, Bonventre JV, Bakker SJ. High Urinary Excretion of Kidney Injury Molecule-1 Is an Independent Predictor of Graft Loss in Renal Transplant Recipients. Transplantation. 2007 Dec 27;84(12):1625-1630. Read Abstract. Zhang PL, Rothblum LI, Han WK, Blasick TM, Potdar S, Bonventre JV. Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury. Kidney Int. 2007 Dec 26. Read Abstract. Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P, Bonventre JV. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2007 Dec 5. Read Abstract.  Technology Wang J, Theunissen TW, Orkin SH. Site-directed, virus-free, and inducible RNAi in embryonic stem cells. Proc Natl Acad Sci USA. 2007 Dec 26;104(52):20850-5. Read Abstract. The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions. Visit our website at www.hsci.harvard.edu. If there is anything that you would like to see added to this email alert, please email maureen_lyons@harvard.edu.

Photo courtesy of B.D.Colen. Copyright © 2007 President and Fellows of Harvard College. All rights reserved.

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Nature Cell Biology contents: February 2008 Volume 10 Number 2, pp 111 - 245

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February 2008 Volume 10 Number 2, pp 111 - 245

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EDITORIAL
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Registries and banks p111
The European Registry for Human Embryonic Stem Cells (hESCreg)
adds an important global resource to the fragmented landscape
of stem cell research.
doi:10.1038/ncb0208-111
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjo0Ex

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NEWS AND VIEWS
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Telomeric RNA enters the game pp113 - 115
Two studies report expression of telomeric-repeat-containing
RNAs in vertebrates. This discovery challenges the long-standing
notion that telomeres are transcriptionally inert.
Beatrice Horard and Eric Gilson
doi:10.1038/ncb0208-113
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjp0Ey

Outsourcing CREB translation to axons to survive pp115 - 118
Nerve growth factor induces sensory neuron survival via
retrograde signalling from the axon to the cell body.
Local translation of the transcription factor CREB in the
axon, followed by its transport to the nucleus,
is involved in this process.
Andrew C. Lin and Christine E. Holt
doi:10.1038/ncb0208-115
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjq0Ez

Facing up to Mena: Tes(ting) times for EVH1 domains pp118 - 120
Ena/VASP family members have a common binding interface
on their EVH1 domains for FPPPP motifs in partner proteins.
The finding that Tes, a protein lacking FPPPP motifs, competes
specifically for the FPPPP ligand site on Mena, provides new
insights into the differential regulation of Ena/VASP proteins.
J. Victor Small
doi:10.1038/ncb0208-118
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjr0E1

Green light for chloroplast outer-membrane proteins pp120 - 122
Most chloroplast proteins are encoded in the cell nucleus,
translated in the cytosol, and targeted to the organelle in a
post-translational manner. Our understanding of how proteins
are targeted to the outer envelope membrane of chloroplasts
has been improved with the identification of a specific
soluble sorting factor.
Jocelyn Bedard and Paul Jarvis
doi:10.1038/ncb0208-120
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjs0E2

Heads or tails: can Wnt tell which one is up? pp122 - 124
Planarian flatworms regenerate their heads and tails after
amputation. It turns out that they use Wnt-beta-catenin
signalling to determine where the head and the tail should form.
Elly M. Tanaka and Gilbert Weidinger
doi:10.1038/ncb0208-122
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjt0E3

ERK and MDM2 prey on FOXO3a pp125 - 126
Constitutively active ERK signalling stimulates cell
proliferation, thereby contributing to tumorigenesis. We
now learn that ERK activity induces phosphorylation and
MDM2-mediated degradation of the tumour-suppressing transcription
factor FOXO3a, thus gaining new information on valuable targets
for human cancer therapeutic intervention.
Wensheng Yang, Nathan G. Dolloff and Wafik S. El-Deiry
doi:10.1038/ncb0208-125
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmju0E4

----------------------
ARTICLES
----------------------
PDK1 regulates cancer cell motility by antagonising
inhibition of ROCK1 by RhoE pp127 - 137
Sophie Pinner and Erik Sahai
doi:10.1038/ncb1675
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjv0E5
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjw0E6

ERK promotes tumorigenesis by inhibiting FOXO3a
via MDM2-mediated degradation pp138 - 148
Jer-Yen Yang et al.
doi:10.1038/ncb1676
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjx0E7
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjy0E8

Intra-axonal translation and retrograde trafficking of
CREB promotes neuronal survival pp149 - 159
Llewellyn J. Cox et al.
doi:10.1038/ncb1677
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmjz0EA
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj10Ev

TBL1-TBLR1 and beta-catenin recruit each other to
Wnt target-gene promoter for transcription activation
and oncogenesis pp160 - 169
Jiong Li and Cun-Yu Wang
doi:10.1038/ncb1684
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj20Ew
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj30Ex

----------------------
LETTERS
----------------------
Wingless secretion requires endosome-to-Golgi retrieval
of Wntless/Evi/Sprinter by the retromer complex pp170 - 177
Xavier Franch-Marro et al.
doi:10.1038/ncb1678
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj40Ey
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj50Ez

Wingless secretion promotes and requires
retromer-dependent cycling of Wntless pp178 - 185
Fillip Port et al.
doi:10.1038/ncb1687
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj60E1
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj70E2

A beta-catenin gradient links the clock and
wavefront systems in mouse embryo segmentation pp186 - 193
Alexander Aulehla et al.
doi:10.1038/ncb1679
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0Bmj80E3
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkA0EE

Nanog maintains pluripotency of mouse embryonic stem
cells by inhibiting NFkappaB and cooperating with Stat3 pp194 - 201
Josema Torres and Fiona M. Watt
doi:10.1038/ncb1680
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkB0EF
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkC0EG

The microRNAs miR-373 and miR-520c promote tumour
invasion and metastasis pp202 - 210
Qihong Huang et al.
doi:10.1038/ncb1681
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkD0EH
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkE0EI

Membrane nanotubes physically connect T cells over
long distances presenting a novel route for
HIV-1 transmission pp211 - 219
Stefanie Sowinski et al.
doi:10.1038/ncb1682
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkF0EJ
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkG0EK

AKR2A-mediated import of chloroplast outer membrane
proteins is essential for chloroplast biogenesis pp220 - 227
Wonsil Bae et al.
doi:10.1038/ncb1683
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkH0EL
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkI0EM

Developmentally regulated transcription of mammalian
telomeres by DNA-dependent RNA polymerase II pp228 - 236
Stefan Schoeftner and Maria A. Blasco
doi:10.1038/ncb1685
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkJ0EN
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkK0EO

Sterol-dependent endocytosis mediates post-cytokinetic
acquisition of PIN2 auxin efflux carrier polarity pp237 - 244
Shuzhen Men et al.
doi:10.1038/ncb1686
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkL0EP
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkM0EQ

----------------------
ERRATUM
----------------------
Erratum p245
doi:10.1038/ncb0208-245
http://ealerts.nature.com/cgi-bin24/DM/y/eiwv0Xztnp0HjD0BmkN0ER

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[StemCells] Stem cell treatment in China - CP children - anyone with first-hand experience

I was considering taking my 3-year old daughter with CP to China for
stem-cell treatment. I was considering going with Beike-biotech.
Anyone with first hand experience of using this treament for children
with CP, please let me know.

If writing a long mail is too tedious I can call.

Looking forward to hearing from someone.

regards
Devina Mehra

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http://groups.yahoo.com/group/CNS_Healing
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