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Archive for the ‘embryonic’ Category

Problem: embryonic stem cell lines vary & iPS lines too

Posted by attilacsordas on June 1, 2008

Finally I started to digest all the articles (usually on the streetcar on my way to work and home) from the recent Nature Insight: Regenerative Medicine and I try to pick up some stories for you (& interesting enough for me) from that, in case you are not lucky enough to have an available copy.

For clinicians, the lack of gold standard embryonic stem cell lines with the measurably same regeneration potential will be a huge technological problem later while this variability is an interesting basic science problem today.

Kenneth R. Chien: Regenerative medicine and human models of human disease

A central challenge to the development of human stem-cell-based models of disease lies in the need to isolate and expand rare cell populations reproducibly and then to fully differentiate enough of the cells of interest. In this regard, one of the main obstacles to establishing human ES-cell-based models is that ES cell lines vary. All lines do not have the same potential to differentiate into cells of a particular lineage, most probably as a result of inherent epigenetic, genetic and developmental differences at the time of their isolation. For example, a study of 17 independent human ES cell lines showed that 7 of these lines had little or no capacity to enter the cardiovascular lineage, and the level of cardiovascular markers expressed by 2 of the 17 cell lines was an order of magnitude or more higher than that of these 7 lines. Similar variability between human ES cell lines was observed for entry to the pancreatic lineage, and cell lines that were optimal for generating cells of endodermal lineages were extremely poor for generating mesodermal lineage cells in many cases. Thus, new human ES cell lines that are optimal for generating specific lineages of interest need to be produced. In addition, iPS cell lines might be similarly variable. Read the rest of this entry »

Posted in biology, embryonic, Nature, regenerative medicine, science, stem cells | 1 Comment »

Out of 8 embryo cells: if 1 turned to an ES cell, 7 could still become a child

Posted by attilacsordas on January 10, 2008

chungetalblastomereAt least I know how to start my stem cell comprehensive exam tomorrow (The trick is to use blastocyst medium supplemented with laminin and fibronectin):

Human Embryonic Stem Cell Lines Generated without Embryo Destruction

Young Chung, Irina Klimanskaya, Sandy Becker, Tong Li, Marc Maserati, Shi-Jiang Lu, Tamara Zdravkovic, Dusko Ilic, Olga Genbacev, Susan Fisher, Ana Krtolica, and Robert Lanza

“To date, the derivation of all human embryonic stem cell (hESC) lines has involved destruction of embryos. We previously demonstrated that hESCs can be generated from single blastomeres (Klimanskaya et al., 2006). In that ‘‘proof-of-principle’’ study, multiple cells were removed from each embryo and none of the embryos were allowed to continue development. Here we report the derivation of five hESC lines without embryo destruction, including one without hESC coculture. Single blastomeres were removed from the embryos by using a technique similar to preimplantation genetic diagnosis (PGD). The biopsied embryos were grown to the blastocyst stage and frozen. The blastomeres were cultured by using a modified approach aimed at recreating the ICM niche, which substantially improved the efficiency of the hESC derivation to rates comparable to whole embryo derivations. All five lines maintained normal karyotype and markers of pluripotency for up to more than 50 passages and differentiated into all three germ layers.”

Legend: “(A) Stages of derivation of hES cells from single blastomere. (a) Blastomere biopsy, (b) biopsied blastomere (arrow) and parent embryo are developing next to each other, (c) initial outgrowth of single blastomere on MEFs, 6 days, and (d) colony of single blastomere-derived hES cells.”

Context link: Wired: Embryonic Stem Cells Created Without Harming Embryo, for Real This Time

Posted in biology, biotechnology, embryonic, science, stem cells, USA | 1 Comment »

California embryonic stem cell dollars: beyond the embryonic phase

Posted by attilacsordas on December 5, 2007

According to the newest Request For Applications (RFA) of the California Institute for Regenerative Medicine (CIRM), the New Cell Line Awards will support two categories of research:

Category 1: Derivation of new hESC lines using excess or rejected early stage human
embryos generated by in vitro fertilization.

Category 2: Derivation of pluripotent human stem cell lines from other sources using
alternative methods such as (but not limited to) SCNT or reprogramming of neonatal or
adult cells (iPS cells).

The real news is encoded in category 2: from now on even adult stem cell research can be backed by California Embryonic Stem Cell Dollars. The same idea in another form in the text:

• disease-specific or otherwise genetically diverse, pluripotent stem cell lines to support
studying the effects of genetic variation on disease mechanism and response to
treatment, and the discovery and evaluation of new drug candidates
• the discovery and implementation of alternative methods for generating pluripotent
human stem cells, including technology leading to the generation of patient-matched or
disease-specific cell lines

What research trend is behind? The generation of induced pluripotent stem (iPS) cells. The successful reprogramming of differentiated human somatic cells into a pluripotent, embryonic stem (ES) cell-like state that would allow creation of patient- and disease-specific stem cells instead of using controversial embryonic stem cells was recently reported by 2 groups of researchers: the Yamanaka and the Thomson lab.

Under this RFA, CIRM intends to commit up to $25 million to support up to 16 awards,
eight (8) in each of the two categories of research. CIRM proposes to fund each award
for up to three (3) years for direct project costs of up to $300,000 per year.

Other side of the story in California Stem Cell Report: California’s Widening Stem Cell Net

Read the rest of this entry »

Posted in california, embryonic, regenerative medicine, science, stem cells, USA | Comments Off

Unofficial and hypercritical peer review of a paper on p53′s role in hESC regulation

Posted by attilacsordas on November 25, 2007

Once I wrote shortly about the following peer review paper which was popped out of my PubMed feeds to draw some attention to it: Han Qin, Tianxin Yu, Tingting Qing, Yanxia Liu, Yang Zhao, Jun Cai, Jian Li, Zhihua Song, Xiuxia Qu, Peng Zhou, Jiong Wu, Mingxiao Ding, Hongkui Deng
Regulation of apoptosis and differentiation by p53 in human embryonic stem cells.
J Biol Chem. 2007 Feb 23;282(8):5842-52
doi:10.1074/jbc.M610464200

abstractQin

Now I got a very thorough comment on this paper by an author nicknamed “wolf” which systematically goes through the paper and gives a highly critical peer review of it. So I just publish the comments and next ask the authors (the first or the last) of the criticized paper and give them the possibility to defend their experiments and statements. My role here is the role of the blog”publisher”.

Comments re Qin paper p53 and hESC apoptosis by “wolf”:

This paper starts with making a fundamental mistake in not determining the kinetics of UV induced apoptosis and therefore missing the modulation of p53 target genes.
Subsequently they attempt to explain the absence of this by using transient transfections and analysing the cells at timepoints when half of the cells (mainly the undiff cells) are already dead and then interpret the data of the differentiated transfected (more resistant) hESC as if they were undiff hESC. The paper then desperately tries to come up with explanations for their own contradictory results). The data set further lacks controls (lentiviral mock transduced cells, no isotype controls etc), uses the wrong assays (such as PI staining to assess apoptosis, morphological assessment of differentiation by surface area) and lacks insight into the mechanisms controlling apoptosis (no cyt c release, no idea how p53 by itself might trigger mitochondrial apoptosis, etc).

Specifically;

Materials and Methods

Page 2: The authors use mainly one line of late passage hESC (p42-p68) grown in KSOR, which are highly CD30 positive leading to alterations in apoptosis regulation. We use three hESC lines at passages before p12 only.

Page 3: endoderm differentiation occurs in 4 days after Activin addition ? This is very quick with >80 % of hESC expressing sox17 after 100 ng/ml activin ?

Page 3: In immunostaining no antibody controls were used instead of isotype control with identical concentrations. We use isotype controls for all our immunos. Read the rest of this entry »

Posted in biology, embryonic, peer-review, science, science publishing, stem cells | Comments Off

The first stem cell related Nobel prize: Martin Evans, 2007

Posted by attilacsordas on October 8, 2007

martinevansThe Nobel Assembly at Karolinska Institute has today decided to award The Nobel Prize in Physiology or Medicine for 2007 jointly to Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries of “principles for introducing specific gene modifications in mice by the use of embryonic stem cells” Link

It’s rather a 2/3 gene technology, 1/3 stem cell methodology Prize, but shows how those technologies are interrelated.

Evans is still an active scientist but here are 2 famous papers he authored or coauthored:

1. First teratocarcinoma paper (always those cancer cells), how to isolate and maintain them, Evans is the single author: The isolation and properties of a clonal tissue culture strain of pluripotent mouse teratoma cells. J Embryol Exp Morphol. 1972 Aug;28(1):163-76.

2. And then the switch to embryonic stem cells a decade later, a protocol lead to the 1998 Science paper by Thomson et al. on human ES cells: Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-6. (1981).

Posted in biology, Cambridge, cancer, embryonic, Nobel Prize, science, stem cells | Comments Off

Vincent van Gogh and human embryonic stem cells

Posted by attilacsordas on September 27, 2007

Let’s continue our Hit art illustrations for scientific slides project this time with van Gogh’s “Starry night“. The slide is from Chang-Kyu Lee’s presentation on the SENS3 conference, entitled Interspecies somatic cell nuclear transfer for establishing embryonic stem cells with desired genotype.

vanGoghandhEScells

Posted in art, embryonic, presentation, SENS3, stem cells | 1 Comment »

George Daley explains the source of Hwang’s “cloned” ES cells on Youtube

Posted by attilacsordas on August 18, 2007

George Daley, the new president of the International Society for Stem Cell Research explains shortly the notorious case on a not embeddable (??????) YouTube video. If you are too busy to read the story, than watch it, it is 2 minutes and 13 seconds. Thanks for the video tip, Alexey Bersenev.

If you have a bit more time to read on:

Hwang’s “clone” was really a parthenote, Daley reports

Posted in biology, celebrity, cell biology, embryonic, history of science, science, science videos, stem cells | 1 Comment »

Donating Frozen Embryos for Stem Cell Research: a survey in Science

Posted by attilacsordas on July 17, 2007

SciencedonatedembryosEMBRYONIC STEM CELLS: Willingness to Donate Frozen Embryos for Stem Cell Research by Anne Drapkin Lyerly and Ruth R. Faden, Science 6 July 2007: Vol. 317. no. 5834, pp. 46 – 47 DOI: 10.1126/science.1145067

We conducted a survey of 2210 infertility patients receiving treatment at one of nine major, geographically diverse infertility centers and asked these patients about their intentions for the embryos they currently stored. Participating centers were located in California, Colorado, the District of Columbia, Maryland, Missouri, New Jersey, North Carolina, Oregon, Pennsylvania, and Virginia. The respondents were asked to answer a set of questions with one of the following: very likely, somewhat likely, somewhat unlikely, very unlikely, or unsure/don’t know.

/Figure legend. Disposition option for some or all of cryopreserved embryos currently stored. SCNT, somatic cell nuclear transfer. Key: Somewhat likely (lavender), very likely (gray).
CREDIT: MIODRAG STOJKOVIC/SCIENCE PHOTO LIBRARY / Read the rest of this entry »

Posted in embryonic, ethics, grant, medicine, regenerative medicine, science, stem cells, USA | 2 Comments »

Prepare for the ISSCR 2007 stem cell party! June, 17-20

Posted by attilacsordas on June 14, 2007

ISSCRniche 5th International Society for Stem Cell Research (ISCCR) Annual Meeting will be held this weekend June 17-20, at the Cairns Convention Centre Queensland, Australia and the schedule is exciting. Unfortunately it is improbable that there will be a pioneer web coverage on this mainstream congress as it happened in the case of the Edmonton Aging Symposium which According to the organizers “was a WORLD FIRST! in being streamed live onto the internet and indeed there was a full video, audio and presentation access. Anyhow, here are 2 more interesting shots from the ISSCR schedule:

ISSCRtumorniche

Read the rest of this entry »

Posted in biology, conference, embryonic, regenerative medicine, science, stem cells | Comments Off

Nature Reports Stem Cells is live from now on…for stem cell enthusiasts

Posted by attilacsordas on June 7, 2007

No more waiting: Nature Reports Stem Cells (NRSC) launched today, and so finally there is a fully web native, scientifically high-end (naturally), freely accessible, all-in-one stem cell research hub site for everyone (especially for the researchers) to read, share, contribute and turn the acquired insights back into new experiments, policies, ethics, businesses and clinical trials.

NRSClaunches

Edited by the devoted small team Natalie DeWitt (Editor at Large), Monya Baker (News Editor) and Jessica Kolman (Editorial Assistant), based in Nature’s San Francisco office, California (where else?) NRSC has a bunch of usual and unusual ways: news, featured editor, journal club with user recommended articles and voting system, interviews, events and the really exciting and experimental Insider the paper section. From the first editorial of NRSC: Inside the Paper posts edited discussions between authors and reviewers during peer review. Such transparency should not only deepen readers’ understandings of individual research publications, it will expose the workings of peer review itself. In the coming months, we plan to launch a Toolbox section will aggregate information on stem-cell protocols, reagents, and cell lines that would otherwise require trawling through literature or having serendipitous conversations at conferences.”

insidethepaperembryonic

Read the rest of this entry »

Posted in Bay Area, biology, embryonic, Nature, Nature Publishing Group, Nature Report Stem Cells, open-access, peer-review, regenerative medicine, science, science journals, science publishing, stem cells, The Niche | 1 Comment »

On CIRM’s Medical and Ethical Standards in Plos Medicine

Posted by attilacsordas on May 29, 2007

Geoffrey P. Lomax, Zach W. Hall, Bernard Lo: Responsible Oversight of Human Stem Cell Research: The California Institute for Regenerative Medicine’s Medical and Ethical Standards

CIRMethical

Source: Plos blog, In the May issue of PLoS Medicine

Posted in Bay Area, biology, biotechnology, california, culture, embryonic, ethics, medicine, open-access, Plos, science, science journals, stem cells, therapy, USA | Comments Off

Anthony Atala on regenerative medicine at New Yorker’s 2012 conference

Posted by attilacsordas on May 27, 2007

Dr. Anthony Atala of pluripotent amniotic fluid-derived stem cell and tissue engineered bladder fame gave a presentation on Regenerative Medicine at the 2007 New Yorker Conference “2012: Stories from the Near Future”.

Atala, the director of the Biopolis-like huge Wake Forest Institute for Regenerative Medicine with circa 150 people, talks amongst others on the differences amongst embryonic, placental and adult stem cells, the differences between the tissue engineering of solid organs (kidney) and hollow organs (bladder) and on the five-year follow-up careful strategy behind the successful tissue engineered products. Here are some slides of the presentation in the order of appearance:

atalanewyorker1

Posted in biology, conference, embryonic, New York, placenta, presentation, regenerative medicine, science, science videos, stem cells, tissue engineering, USA, video | 3 Comments »

Stem Cell Cup: California Embryonics vs Massachusetts Oldies: $3 vs $1.25 Billion

Posted by attilacsordas on May 10, 2007

gameplan While people in California can think they are in the centre of the (embryonic) stem cell universe due to Proposition 71′s $3 Billion and the invasion of good scientists into the West Coast, Massachusetts academic and biotech people also are thinking along those lines, so state officials quickly set up a $1.25 Billion package for funding stem cell research in the very state and “establishing the first stem cell bank, a repository of all the stem cell lines created in Massachusetts laboratories, which would serve as a kind of stem cell lending library to scientists around the world. “

Links:

Massachusetts floats $1 bln stem cell research plan (Reuters)

Massachusetts Proposes Stem Cell Research Grants (New York Times)

Posted in Bay Area, biology, biotechnology, california, embryonic, grant, regenerative medicine, science, stem cells, USA | Comments Off

2 models of embryonic and adult blood formation: Figure by Ueno and Weissman

Posted by attilacsordas on May 10, 2007

If you have previously thought (in your spare time) that the conventional wisdom concerning blood formation is that the yolk sac’s embryonic blood-forming cells serve only the embryo, while the source of adult blood-forming stem cells is the region called aorta-gonad-mesonephros (AGM), it’s time to think it again due the elegant experiments of Samokhalov et al.: Cell tracing shows the contribution of the yolk sac to adult haematopoiesis Nature 446, 1056-1061 (26 April 2007)

bloodformationuenoweissman

Legend: a, The ‘separate’ model. Read the rest of this entry »

Posted in biology, blood, development, embryonic, hematopoiesis, Nature, peer-review, science, stem cells | Comments Off

Stem Cell Research Budget Cutting in Florida

Posted by attilacsordas on May 3, 2007

It is just $20 million but look at the policy behind: Stem cell research faces budget shortfall

Posted in embryonic, grant, politics, stem cells, USA | Comments Off

First differentiated cell types in mammals are…

Posted by attilacsordas on April 27, 2007

blood cells, “generated in early-stage embryos, for instance in mice in the yolk sac at embryonic day (E) 7.0.-7.5, just 2 or 3 days after the undifferentiated conceptus implants in the uterus.” Source: Ueno-Weissman: Blood lines from embryo to adult Nature 446, 996-997 (26 April 2007)

Posted in biology, blood, development, differentiation, embryonic, onesentence, science | Comments Off

Stories from my PubMed feeds: hESCs, p53, apoptosis and differentiation

Posted by attilacsordas on April 23, 2007

Short peer-review storytelling : One big technical problem of human embryonic stem cells (hESCs) (in contrast to mouse embryonic stem cells) that hESCs normally undergo high rates of spontaneous apoptosis and differentiation, making them difficult to maintain in culture. Now we are getting to know a bit more on the molecular background of these processes. In an article in the prestigious Journal of Biological Chemistry Qin et al.’s studies reveal the important roles of p53 as a critical mediator of human embryonic stem cells survival and differentiation.

Regulation of apoptosis and differentiation by p53 in human embryonic stem cells.

J Biol Chem. 2007 Feb 23;282(8):5842-52

“Here we demonstrate that p53 protein accumulates in apoptotic hESCs induced by agents that damage DNA. However, despite the accumulation of p53, it nevertheless fails to activate the transcription of its target genes. This inability of p53 to activate its target genes has not been observed in other cell types, including mESCs. We further demonstrate that p53 induces apoptosis of hESCs through a mitochondrial pathway. Reducing p53 expression in hESCs in turn reduces both DNA damage-induced apoptosis as well as spontaneous apoptosis. Reducing p53 expression also reduces spontaneous differentiation and slows the differentiation rate of hESCs.”

Figure 2 for the pros:

Read the rest of this entry »

Posted in biology, embryonic, mitochondria, peer-review, science, science journals, stem cells | 1 Comment »

What is the birth date of present day stem cell biology?

Posted by attilacsordas on April 3, 2007

thomsonetalpicIf there is any? Stem cell biology and regenerative medicine as an institutionally specified discipline is quite young, about a decade old. Bone marrow transplantation traces its roots back to the 1970-s, but many people don’t realize that it is the most useful although restricted form of stem cell therapy till this day. In my opinion the birth date of present day stem cell biology is Thomson et al.’s 1998 November paper in Science on Embryonic Stem Cell Lines Derived from Human Blastocysts.
Not because it was so original. It is known that much of the embryonic stem cell isolation protocol and the in vivo teratoma forming as pluripotency test came from two papers by Cambridge biologists, appeared in 1981 that reported the derivation of pluripotent stem cell lines from cultured mouse embryos. But the Thomson results were based on human cells and this is a crucial difference concerning potential regenerative therapies as it was discussed in the paper: “The standardized production of large, purified populations of euploid human cells such as cardiomyocytes and neurons will provide a potentially limitless source of cells for drug discovery and transplantation therapies. Many diseases, such as Parkinson’s disease and juvenile-onset diabetes mellitus, result from the death or dysfunction of just one or a few cell types. The replacement of those cells could offer lifelong treatment.” Also the timing of the paper was good. The 2 Cambridge papers, which were also mentioned as references in the Thomson et al. paper.:
Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-6. (1981).
Martin, G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA 78, 7634-7638 (1981).

In your opinion: What is the birth date of present day stem cell biology? Is there any discrete point? How would you locate the beginnings of stem cell science in time and space?

Posted in biology, embryonic, history, history of science, regenerative medicine, science, stem cells | 1 Comment »

Competitive strength of California Institutions measured by stem cell grants

Posted by attilacsordas on March 18, 2007

Press Release of California Institute of Regenerative Medicine: LOS ANGELES, March 16, 2007 – “Just a month after approving nearly $45 million for embryonic stem cell research, California’s stem cell agency authorized another $75.7 million in additional funds for established scientists at 12 non-profit and academic institutions.”

With this latest round of CIRM donation more than $158 million has been approved for research grants at 23 California institutions. From this table below (from the press release) we can guess the competitive strengths of the universities and research institutes:

Californian Stem Cell Institution Hierarchy

Read the rest of this entry »

Posted in Bay Area, biology, biotechnology, california, embryonic, grant, regenerative medicine, science, Stanford, USA | Comments Off

Functional blood vessels from hESCs durable for at least 151 days

Posted by attilacsordas on February 28, 2007

A really pushing-the-limits paper published by the Scadden lab as a Brief Communication in Nature Biotechnology Advance Online, just like the De Coppi, Atala et al. paper on human amniotic stem cells in January. This time human embryonic stem (hES) cells were differentiated into endothelial cells using a scalable step-by-step two-dimensional method, avoiding the formation of three-dimensional (3D) embryoid bodies from the cells and the inefficient spontaneous differentiation. The selected culture cells were labeled with enhanced green fluorescent protein (EGFP) to track their in vivo life after transplantation into immunodeficient (SCID) mice (see the green visualization on the picture). The differentiated cells were able to form functional blood vessels in vivo and contributed to arborized blood vessels that integrated into the host circulatory system and served as blood conduits for 150 d”. Zack Z Wang, Patrick Au, Tong Chen, Ying Shao, Laurence M Daheron, Hao Bai, Melanie Arzigian, Dai Fukumura, Rakesh K Jain & David T Scadden: Endothelial cells derived from human embryonic stem cells form durable blood vessels in vivo

hESCvesselWang

Significance: Scalability in tissue engineering, Read the rest of this entry »

Posted in biology, biotechnology, blood, embryonic | Comments Off

Public list of researchers behind the first approved embryonic stem cell grants in California

Posted by attilacsordas on February 19, 2007

sacramentoLittle history: SAN FRANCISCO, February 16, 2007 – The governing board of the California Institute for Regenerative Medicine (CIRM) approved 72 grants totaling approximately $45 million over two years, to researchers at 20 academic and non-profit research centers throughout the state focused solely on human embryonic stem cell research.
So here is what the future of embryonic stem cells looks like: Stanford scholars were preferred the most by CIRM, in the first run 12 grants worth a combined $8 million were distributed to them. Well, I wouldn’t be surprised too much if the founders of the coming Google Incorporation of Regenerative Medicine in the biotechnology industry were from Stanford University also.
38 projects have been already listed and linked that were recommended for funding. But now from the press release pdf at the CIRM website we are finally informed about the names of the researchers who will carry on the projects. It is also an excellent career guide for young stem cell researchers, undergraduates, graduates, postdocs who are eager to work in California. Surprisingly there are scholars, who are completely new in stem cell research, but would like to put it in a multidisciplinary context. A good example is Gregory T. A. Kovacs electrical engineering professor from Stanford, who will develop cell-monitoring technologies that would provide a better understanding of cardiomyocyte differentiation from human embryonic stem cells (hESC), identify optimal stages of differentiation for cell-transplantation therapy, and perhaps facilitate directed in vitro differentiation strategies.
The list is public:

pplication#   Principal Investigator   Institution   Title   Amount
RS1-00161-1   Blelloch, Dr. Robert Hector   University of California, San Francisco   MicroRNA Regulation of Human Embryonic Stem Cell Self-Renewal and Differentiation   $631,831
RS1-00163-1   Bredesen, Dr. Dale Eric   Buck Institute for Age Research   Programmed Cell Death Pathways Activated in Embryonic Stem Cells   $734,202
RS1-00169-1   Cashman, Dr. John R.   Human BioMolecular Research Institute   Discovering Potent Molecules with Human ESCs to Treat Heart Disease   $714,654
RS1-00170-1   Chen, Dr. Bin   University of California, Santa Cruz   In vitro differentiation of hESCs into corticospinal motor neurons   $500,000
RS1-00171-1   Chen, Dr. Huei-Sheng Vincent   Burnham Institute for Medical Research   Development of Neuro-Coupled Human Embryonic Stem Cell-Derived Cardiac Pacemaker Cells.   $744,639
RS1-00172-1   Chen, Dr. Irvin S.Y.   University of California, Los Angeles   Genetic modification of the human genome to resist HIV-1 infection and/or disease progression   $642,652
RS1-00173-1   Chien, Professor Shu   University of California, San Diego   Combinatorial Platform for Optimizing Microenvironments to Control hESC Fate   $638,140 Read the rest of this entry »

Posted in Bay Area, biology, biotechnology, california, embryonic, regenerative medicine, science, stem cells | Comments Off

Early progenitor cell number as organ size determinant: pancreas

Posted by attilacsordas on February 14, 2007

Developmental biology is the gold mine of stem cell biology. A pioneer, but elegant quantitative cell biology paper was published in Nature advance online publication on 28, January 2007 by U.S. researchers Stanger, Tanaka, Melton along developmental lines.
Based on the strict regulation of vertebrate development it was thought that extrinsic or systemic signals, growth factors and apoptotic factors have a decisive role in determining and restoring the final size and shape of an organ even after big cellular loss during embryogenesis and regeneration. Extrinsic signals regulate size in many vertebrate tissues, including blood, liver, muscle and the central nervous system by controlling cell proliferation or by modulating cell death. Not in mice’s pancreas! Two different methods—cell ablation and tissue complementation—were used to perturb precursor cell number during the earliest stages of pancreatic and liver development. Liver was chosen because of its close developmental relationship to the pancreas. Transgenic mice strains were used, in which pancreatic and hepatic progenitor cell number can be regulated, ablated, restored. To assess the capacity for compensatory growth, embryos were generated in which many, but not all, progenitor cells were ablated.

Setting aside the complicated (really) technological details it was showed, that “compensatory growth during pancreas development is either quite limited or does not occur at all. Thus, embryonic progenitor cells represent a critical and limiting determinant of pancreas size. Read the rest of this entry »

Posted in biology, embryonic, peer-review, quantitative, science, stem cells, USA | Comments Off

Studies recommended for funding by California Stem Cell Rush dollars

Posted by attilacsordas on February 7, 2007

The working future of embryonic stem cell biology and regenerative medicine is in the 38 projects listed and linked below. Or at least in some of them. These are the research projects that were recommended for funding available by the California Institute for Regenerative Medicine after a thorough evaluation and all applications can be found in the Public List of CIRM. 47 more were recommended for funding if money is available. If you choose to scan through the public abstracts of the proposal (linked with the numbers) I also strongly recommend to read the WEAKNESSES part of the review. The order of the projects is descending from the highest scientific score (out of 100) to the lowest.

96 Generation of forebrain neurons from human embryonic stem cells RS1-00205-1

95 The APOBEC3 Gene Family as Guardians of Genome Stability in Human Embryonic Stem Cells RS1-00210-1

95 Generation of hESC lines, under defined conditions, modeling normal & diseased states from material stored at the Burnham shared embryo bank. RS1-00305-1

94 Gene regulatory mechanisms that control spinal neuron differentiation from hES cells. RS1-00288-1

93 Mitochondrial Dysfunction in Embryonic Stem Cells RS1-00432-1 Read the rest of this entry »

Posted in Bay Area, biology, california, embryonic, foundation, grant, regenerative medicine, science, stem cells, USA | 5 Comments »

How to isolate amniotic stem cells from the placenta, at home!

Posted by attilacsordas on January 23, 2007

/Thanks for spreading the idea of biotech diy: Make, Pharyngula, kottke.org, Scientific American Blog, BoingBoing, Digital Bio, Clock among others…/

The placenta is a very valuable and scarce human tissue, although the proper recycling of it is not placentophagy, but the isolation of stem cells from its amnion layer, and storing them for later regenerative purposes for the whole family. Human amniotic epithelial cells (HAECs) from the placenta are alternative replacements of human embryonic stem cells, and have the potential to differentiate to all three germ layers in vitro. These cells are very close to those earlier and broadly multipotent amniotic fluid-derived stem cells, which made the big buzz lately on the web, published by De Coppi, Atala et al. in Nature Biotechnology. Here I would like to show, although I do not provide any warranty and can not give any guarantee, that isolating stem cells from the placenta is not more difficult than making a steak, and with proper preparation, investment and timing you can do it even at home or in a rent lab. The process is ethically non-controversial since the placenta is usually discarded after birth. Today, stem cell therapy is just a promising possibility, but in the not so distant future, self-aware citizens may manage their own stem cells, grow them in the garage, and store them in the fridge. If so, it could be a form of autonomous medical self-insurance. We are at the dawn of the bioDIY movement backed by open source science for anybody. I used Make magazine’s Backyard Biology issue as a reference, because it invented the basic language of bioDIY or home or garage biotech. Here is the algorithm at the cartoon and below are the detailed, although not self-including textual protocol. More details will come later, if asked.

isolatestem

Read the rest of this entry »

Posted in biodiy, biology, biotechnology, diy, embryonic, lifehacks, medicine, open source, placenta, regenerative medicine, science hacks | 80 Comments »

Symbolic and embryonic NIH grant to Advanced Cell and Burnham Institue

Posted by attilacsordas on January 17, 2007

Press release: Advanced Cell Technology, Inc. a leader biotech company in human embryonic stem (ES) cell technology concerning regenerative medicine, has been awarded a research grant from the National Institutes of Health (NIH) in the amount of $204,439 in conjunction with a research project currently underway with one of its academic partners, The Burnham Institute of Medical Research (Burnham Institute).

Grant title: “Directed Differentiation of Embryonic Stem Cells using Phage Displayed Ligands”. From the press release: The project unites Advanced Cell’s expertise in embryonic stem cell biology, phage display, phage targeting technology and gene discovery, with Burnham Institute’s expertise in developmental biology, cardiac biology, and vascular biology, among others. Phage display is a powerful tool that extends the range of modern combinatorial screening techniques, allowing the discovery and characterisation of proteins that interact with a desired target. Briefly: the aim of the project is “to use phage display as a tool to discover novel molecules for directing stem cells to form useful cell types and tissues”.

I have serious doubts on what can achieve with 200 thousand bucks only in this area of research (think about the million dollar annual budget of stem cell labs, the $3 billion in California, and the over $27 billion annual investment budget of NIH) but I am not reluctant to admit the symbolical and political gesture behind this NIH grant.

Posted in california, embryonic, grant, NIH, regenerative medicine, science, stem cells, USA | Comments Off

Best talk at Cambridge today, Austin Smith: self-renewal is default

Posted by attilacsordas on December 20, 2006

Is is easy to realize on a conference when you are hearing a good talk. The audience starts to take notes and gets focused. That happened today during Austin Smith‘s talk (look at Day 1 picture). Straightforward, not overcomplicated line of thought presented by easily conceivable, step by step slides, and hardcore science (facts). These are the elements of a compelling scientific argument. Starting with a dogma, which is that the default in vitro state of embryonic stem cells without any additional factor is neural differentiation, attacking this dogma through carefully executed independent experiments, and proposing a replacement claim: in the case of culture grown hESCs self-renewal is the default state. The “neural commitment by default” is a constructive dogma anyway, it can give rise to nice hypotheses because it captures the imagination with its counterintuitive offer: undifferentiated, pluripotent, self-renewing cells become neural type of cells in normal simple medium by themselves, although neurons are one of the most specialized cell type of the human body, and the nerve system is a young organ system measured on the scale of philogenesis.

Another fruit of the talk for me was meeting with the term “stiff upper lip“. Thanks, Hannah.

Posted in biology, Cambridge, conference, embryonic, presentation, regenerative medicine, science, stem cells | Comments Off

Cambridge Embryonic Stem Cell Symposium, Day 1

Posted by attilacsordas on December 19, 2006

Wow, the promo materials are extremely good (background: my favourite logical towel)

naturepromo

And when people are watching….speakers (like here Austin Smith, the leader of the Wellcome Trust Center for Stem Cell Research) try to say interesting things…

confsmith

Best talk point goes to Allan Bradley, Martin Evans‘ disciple – in science these genealogical tales really matter – who summarized Evans’ tuition in a short form: ambition, independence, invention.

At the poster session I got many valuable and useful comments from my fellow colleagues, thanks for that.

More dry details here in press release style.

 

Posted in biology, Cambridge, conference, embryonic, Nature, regenerative medicine, science, stem cells | Comments Off

Cambridge Embryonic Stem Cell Symposium promoted by Nature

Posted by attilacsordas on December 15, 2006

18-19, December, Babbage Lecture Theatre, Cambridge: Opening Symposium including “A celebration of 25 years of embryonic stem cell research in Cambridge” From the intro: In 1981 two papers appeared that reported the derivation of pluripotent stem cell lines from cultured mouse embryos (1, 2). Now called embryonic stem (ES) cells, they have since transformed research in mammalian development, genetics, stem cell biology and regenerative medicine. Program here. I’ll have a poster there. :) The 2 papers:

  1. Evans, M. J. & Kaufman, M. H. Establishment in culture of pluripotential cells from mouse embryos. Nature 292, 154-6. (1981).
  2. Martin, G. R. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc. Natl. Acad. Sci. USA 78, 7634-7638 (1981).

Posted in biology, Cambridge, conference, embryonic, regenerative medicine, science, stem cells, UK | Comments Off

Adult stem cells and astronauts in the ISS with one screwdriver

Posted by attilacsordas on December 13, 2006

califmapAllowing research into the medical uses of adult stem cells, but not embryonic stem cells, is the equivalent of sending astronauts to work on the international space station with a single tool” according to Dr. Geoffrey Lomax, senior officer for medical and ethical standards of the California Institute for Regenerative Medicine, running California’s $3 billion stem cell research program. Link

Well, if we ever would like to use stem cell therapy to extend healthy lifespan through continuous regeneration of every organ and tissue we have to use probably all available forms and sources of stem cells.

2 unintended consequences of stem cell research via Lomax’s MIIS talk yesterday:

i., Improved therapeutic techniques can drive medical costs up, because all patients will want the new, expensive cures.

ii., Intellectual property questions have arisen over who or what agency “owns” the fruits of stem cell research financed by the taxpayers.

Posted in Bay Area, biology, california, embryonic, foundation, grant, medicine, politics, regenerative medicine, science, stem cells, USA | Comments Off

Real arguments not just echo chambering in embryonic stem cell funding debate

Posted by attilacsordas on December 11, 2006

brandonFinally a journalist at Wired, Brandon Keim thought it’s time to check out some facts and formulate real arguments in the embryonic stem cell funding debate instead of boondoggling. He has collected good historical examples of long-term funding in drug research, which then saved many lives, like Taxol, and has enumerated fields of promising science, like proteomics, gene therapy and nanotechnology which are heavily donated with hundreds of millions of dollars by federal government, although as unproven yet as regenerative medicine based on embryonic stells. Thank you Brandon it is really wired. Link

“A favorite argument as to why the federal government should not fund embryonic stem cell research is that the science is unproven. It has not led to any cures or FDA-approved treatments. That happens to be true. But that doesn’t make it a good argument. In fact, most of the science funded by the federal government is not successful yet, since proven science doesn’t usually need funding.”

Posted in Bay Area, biology, embryonic, FDA, foundation, grant, history of science, medicine, regenerative medicine, society, stem cells, therapy, USA, Wired | Comments Off

Whatbox, Upper Lost Side, Stem Cell Connect-icut (weekend back links)

Posted by attilacsordas on December 10, 2006

starbucks feeling at borders, CambridgeLinks I enjoyed recently all from mainstream media:

San Fransisco Chronicle: THE LOST TAPES Conversations tape-recorded in the early years with Google’s founders illuminate how their actions forged the growth of a Silicon Valley giant via Philipp Lenssen’s blog.

New York Magazine: The Death of (the Idea of) the Upper East Side by Jay McInerney via random choice at Borders‘ Starbucks in Cambridge (see Photo Booth picture), while drinking a Venti Gingerbread Latte.

The New York Times: Connecticut Takes a Lead in Stem-Cell Research Aid via gmail from Anna.

Quotes from the articles:

San Fransisco Chronicle: Question: What other names were considered? Sergey Brin: I think the previous contender to that was called the “Whatbox,” which would have been OK. But then we decided that “Whatbox” sounded like “Wetbox,” which sounded like some kind of a porn site or something, and we decided to stay away from that. Actually the old version of the system was called Backrub. That was because our technology had to do with looking at the link structure of the Web and looking at the backlinks — which pages link to what pages. So Backrub was sort of an immature technology and we turned the idea of looking at backlinks into a search engine. Read the rest of this entry »

Posted in blog, embryonic, general links, journalism, media, stem cells, US, USA | 4 Comments »

London Regenerative Medicine Network Meeting, 13th Dec., King’s College

Posted by attilacsordas on December 7, 2006

spacetime coordinates: 6.00 pm Wednesday 13th December 2006, King’s College London, Guy’s Hospital Campus at London Bridge, London SE1. REGISTRATION IS FREE. Link (funny, Apple-type site)

AGENDA:
18.00 – Registration + networking over tea and coffee
18.30 – Welcome – Dr. Stephen Minger (KCL) – Co-organiser – LRMN
18.35 – “Retinal repair by transplantation of photoreceptor precursors: implications for stem cell therapy” – Prof. Robin Ali – Institute of Ophthalmology/Moorfields Eye Hospital
19.05 – “Tissue Engineering: Great Expectations” – Prof. Michael Lysaght – Brown University, RI, USA and President-Elect of the American Society of Artificial Internal Organs
19.35 – “Development of human embryonic stem cell technology for human therapeutic application” – Dr. Anthony Davies, Geron Corporation, CA, USA
20.05 – Closing remarks – Chris Mason (UCL) – Co-organiser – LRMN

To reserve a place, please just email the LRMN Network Secretary, Dr. Louise Mason: louise.mason@regenmednetwork.com

Posted in biology, biotechnology, conference, embryonic, London, regenerative medicine, science, stem cells, tissue engineering, UK | Comments Off

hESCs derived from single blastomere by Lanza et al.: second trial in Nature with success

Posted by attilacsordas on November 29, 2006

In science you can always correct yourself. In stem cell research it is of utmost importance to correct what you’re claiming, if you’ve claimed it not accurately enough before. Now in November 23 Nature magazine the Lanza group has a corrected manuscript on Human embryonic stem cell lines derived from single blastomeres on the possibility to generate human embryonic stem cells from a single cell that is isolated from an in vitro eight-celled embryo during routine preimplantatation genetic diagnosis (PGD). So it is an ethically non-controversial way to collect human embryonic stem cells, although it is working only in the case of in vitro fertilized embryos. Safety concerns of the protocol are perturbations of genomic imprinting due to the longer time the embryo remains in vitro during the process. As Joe Leigh Simpson says in the News and Views commentary: “This work with human blastomeres follows a demonstration by the same group that ES cells can be derived from single mouse blastomere. In these earlier mouse experiments, an intact viable embryo developed that consisted of the seven remaining blastomeres; by contrast, in the work with human cells, multiple blastomeres were taken from the 8-cell stage and no embryos were allowed to remain in culture. This was a source of confusion in the earlier online publication.”

See also: Editor’s Summary, Bodyhack, New York Times

Posted in biology, embryonic, Nature, peer-review, regenerative medicine, science, stem cells, US, USA | Comments Off

Election perspectives in tech support: New York City as California’s rival in stem cell billions?

Posted by attilacsordas on November 9, 2006

Check this fresh Wired review about US Midterm elections’ effects on high-tech possibilities for the United States: In New York, Attorney General Eliot Spitzer‘s gubernatorial victory was no surprise, but it’s a big win for stem-cell research in that state. Spitzer wants to commit several billion dollars of the state’s money to the science. Link I’ve heard about only 1 billion.

Posted in Bay Area, california, embryonic, foundation, grant, politics, regenerative medicine, science, stem cells, technology, US, USA | 1 Comment »

Blogterview with Fight Aging!’s Reason: answers to life extension questions

Posted by attilacsordas on October 31, 2006

Our first answerer to the 6 questions is Reason, who is the main driving force of the biggest and most established life extension site, Fight Aging! (Technorati Rank) and The Longevity Meme, continuously from 2001.

1. What is the story of your life extension commitment?

I don’t like the idea of decaying, suffering and dying. I reached the point in life at which you realize you can make a difference. The rest is just logic.

2. Is it a commitment for moderate or maximum life extension?

communityAs much as possible. I endorse the concept presently known as actuarial escape velocity (de Grey), a bridge to a bridge (Kurzweil), the step by step approach, etc. The essence of the idea has been around for longer, but it’s getting more press these days; if the next advance increases your healthy life span enough, then you will be able to benefit from the life extension granted by the advance that follows. At some point, the ability to repair the damage of aging increases more rapidly than the damage accrues – and then we are ageless.

It is an open question as to whether this process will get underway soon enough for those young today. But it certainly won’t if we fail to organize and accomplish meaningful goals. None of the science, advocacy or fundraising is particularly hard or strange; it’s “just” going to require a great deal of work, money and infrastructure to get the job done. That fact didn’t stop the cancer research advocates, and it shouldn’t stop us.

3. What is your favourite argument supporting human life extension?

That it is possible, that it harms no-one, and that some people want to do it. No action needs any further argument or justification. Read the rest of this entry »

Posted in anti-aging, blog, community, concept, embryonic, FDA, life extension, longevity, movement, partial immortalization, pimm, regenerative medicine, society, stem cells, technology | 3 Comments »

What would happen if Bill Gates invested 3 billion dollars to embryonic stem cell research?

Posted by attilacsordas on October 27, 2006

beggarThere is a dense comment debate on Bodyhack for more than a week concerning the electoral Missouri Stem Cell Hunter issue, celebs with ESC pro- or contra ads.
Here is an effective comment from today’s related post by the commenter named Orrin:

“I wonder what would happen if Bill Gates invested 2 billion dollars to embryonic stem cell research and just got people to shut up. I’m sure there would be those who accused him of murdering babies while others would say that is still isn’t enough money.

Well, Bill Gates is now a full-time charity man, which makes him more attractive in the eyes of many people, comparing to the times when he was a chief technology officer or software architect at a company. It was in a William Gates III building, as I know from the the Google story, where the PageRank algorithm was born, for example. In the case of embryonic stem cell research, we do not really know the opinion of Mr. Gates, but I think this would be really a useful celeb opinion to know.

Interestingly the Gates Foundation has already put a little money, with 3 zero minus than 3 billion in embryonic research, but in China, not in the U.S.: Still, some billionaires have shied away from this science scrap. Bill Gates’ foundation, the largest in the world with $29 billion on hand, has put less than $2 million into research on human embryonic cells–at a lab at Peking University in China. Researchers there are implanting human cells in mice to look for better ways of making vaccines against aids and hepatitis C. A spokesperson for the Gates Foundation says the Peking researchers hit on the right idea; that the foundation hasn’t funded a single stem-cell test in the U.S., she adds, isn’t related to the anti-abortion fight.
So if Mr. Gates does agree with the purposes of embryonic stem cell research, than it is time to invest big bucks in it. Who knows, maybe this contribution could decide the debate in the U.S….

Posted in biotechnology, business, celebrity, charity, economics, embryonic, grant, IT&BT, medicine, politics, society, stem cells, US, USA | 1 Comment »

New England All-Stars Award goes to Advanced Cell’s Lanza

Posted by attilacsordas on October 25, 2006

Dr. Robert Lanza, vice president of Research and Scientific Development for Worcester-based Advanced Cell Technology (ACT), will be honored at the 11th annual Mass High Tech All-Stars Awards Networking Reception on lanzaWednesday at the category biotechnology. Link
Lanza is a key person in American human embryonic stem cell technology. Some public rearguard actions of the ACT’s controversial Nature Publication on the derivation of hESCs from a single cell without destroying an embryo, can be found here and here. Main point is the possibility to generate human embryonic stem cells from a single cell that is isolated from an embryo during routine preimplantatation genetic diagnosis (PGD).
The award could be interpreted as an East Coast support for Lanza and co. arm-in-arm with embryonic stem cell research. Meanwhile parts of the ACT labs are now in California: “To accelerate its development programs, the article noted that ACT recently moved to California. If you’re going to survive you must be close to the capital,” said William Caldwell IV, CEO of ACT.

Image source

Posted in biotechnology, embryonic, industry, stem cells, US, USA | Comments Off

Stem cell-related videos: the sides of (how many) coins?

Posted by attilacsordas on October 24, 2006

As time goes by stem cells not just become more and more political, but a part of pop culture beyond the scientific experiments.

Posted in community, culture, embryonic, ethics, society, stem cells, US, USA, video | 2 Comments »

FDA Stem Cell Therapy Regulation: the Framework

Posted by attilacsordas on October 19, 2006

Dina Gould Halme and David A. Kessler wrote an article, called FDA Regulation of Stem-Cell–Based Therapies in The New England Journal of Medicine. The key concerns are:

fdai., Stem-cell–based products as therapeutic agents are or could be: biologic products, drugs, devices, xenotransplantation products, human cells, tissues, and cellular and tissue-based products. Human cells, tissues, and cellular and tissue-based products is defined as “articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient.”

ii., Donor’s risk of transmitting infectious or genetic diseases

iii., Contamination or damage risk of the cell or tissue processing: expansion or differentiation of the cells are minimal manipulations, nonhuman fetal calf serum as possible prion source, anymal feeder cells, karyotypic =genetic stability through passages,

iv., Cell types: purity, potency, characterization, the expression pattern of identifying markers

v. In vivo safety and efficacy: experiments in animal models, tumorigenicity

vi., Stem-cell–based products and gene therapy

Link

Image source

Posted in biotechnology, embryonic, FDA, industry, law, medicine, Mprize, patent, politics, regenerative medicine, regulation, society, stem cells, therapy, treatment, US, USA | Comments Off

Embryo research history to understand the Science effect

Posted by attilacsordas on October 18, 2006

Read the rest of this entry »

Posted in embryonic, entropy, history, history of science, philosophy, religion, science, USA | 12 Comments »

 
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