Monday, 9 December 2013
New York Stem Cell Foundation and Personalgenomes.org working together to accelerate research
Monday, 09 December 2013
Today, the New York Stem Cell Foundation (NYSCF) Research Institute and PersonalGenomes.org announced a partnership to identify genetic and environmental contributions to trait and disease development. Cell lines generated by NYSCF will complement genomic data and medical histories contributed by participants in the Harvard Personal Genome Project (PGP), creating a unique and powerful resource to help researchers identify causes of disease.
"Mapping human genetics has laid the groundwork for personalized medicine to tailor treatments to patients on a level not previously achievable. And, now with stem cells, we can take this a step further: we can test and refine drugs on a patient's actual diseased cells," said Susan L. Solomon, CEO of NYSCF.
"Our challenge, going forward, is to leverage the tremendous amount of information from the PGP as the world's only open access source of human genome, microbiome and disease data into a resource for testing causes and cures. We are using PGP stem cells for studying human mutations, gene editing therapies, and novel transplantation methods. That is why we see such value in the integration of these new stem cell technologies through this partnership with NYSCF," said George Church, PhD, Professor of Genetics Harvard Medical School and Founder of the PGP.
To achieve this goal, NYSCF scientists will generate stem cell lines from skin samples of participants in the Harvard PGP. These cell lines can then be studied and compared to data gathered by the PGP including whole genomes, medical histories, body microbiomes and hundreds of other traits from over 3,000 participants. This tool will help achieve the joint goal of "functionalizing" personal genetics for all individuals, meaning using personal genetic information to make informed medical and health decisions.
In 2001, the Human Genome Project (HGP) finished the first draft of the human genome, sequencing most of the 3 billion base pairs that compose human DNA. This took over ten years and cost nearly $3 billion. Today, human genome sequencing is higher quality and can be completed in a day for a little over $1000 enabling researchers an unprecedented look at the building blocks of both normal development and disease.
To additionally speed up the pace of discovery, the PGP developed the open consent framework which enables research studies to make genetic and medical data freely available online to the public and for researchers to analyse and begin to tie underlying genetic patterns or sequences to the development of traits and diseases. Similarly, NYSCF makes cell lines available to researchers in its efforts to find treatments and cures for disease.
Initially, 50 PGP participants will donate skin samples for generation of induced pluripotent stem (iPS) cell lines, which are genetically matched, self-renewing cells that can become any of the body's cell types. Clinicians at dermatology clinics will perform a punch biopsy, a minor procedure to obtain a skin sample, on consenting participants.
These skin samples are then sent to the NYSCF Research Institute, where scientists will derive iPS cells using the NYSCF Global Stem Cell Array™, a novel robotic technology that automates the generation of iPS cell lines. Unlike traditional, by-hand methods to procure stem cells, the Array create standardized, quality controlled cells, enabling scientists to compare stem cells from different participants.
NYSCF scientists will take these iPS cells and derive different adult cell types of interest for research investigations. These cells, which reflect the participants' genetics, provide a powerful tool to study how genetic differences between people can affect disease development and trait expression. Additionally, NYSCF will make these cells available to the broader scientific community through the NYSCF repository.
"Overlaid with medical data, these stem cell models provide a more complete picture of each participant, effectively functionalizing stem cell technology," said Scott Noggle, PhD, Director of the NYSCF Laboratory and NYSCF – Charles Evans Senior Research Fellow for Alzheimer's Disease.
Source: New York Stem Cell Foundation
Contact: David McKeon
For more on stem cells and cloning, go to CellNEWS at
Saturday, 7 December 2013
Researchers from the University of Bonn use reprogrammed patient neurons for drug testing
Saturday, 07 December 2013
Why do certain Alzheimer medications work in animal models but not in clinical trials in humans? A research team from the University of Bonn and the biomedical enterprise LIFE & BRAIN GmbH has been able to show that results of established test methods with animal models and cell lines used up until now can hardly be translated to the processes in the human brain. Drug testing should therefore be conducted with human nerve cells, conclude the scientists. The results are published by Cell Press in the journal Stem Cell Reports.
In the brains of Alzheimer patients, deposits forms that consists essentially of beta-amyloid and are harmful to nerve cells. Scientists are therefore searching for pharmaceutical compounds that prevent the formation of these dangerous aggregates. In animal models, certain non-steroidal anti-inflammatory drugs (NSAIDs) were found to a reduced formation of harmful beta-amyloid variants. Yet, in subsequent clinical studies, these NSAIDs failed to elicit any beneficial effects.
"The reasons for these negative results have remained unclear for a long time", says Prof. Dr. Oliver Brüstle, Director of the Institute for Reconstructive Neurobiology of the University of Bonn and CEO of LIFE & BRAIN GmbH.
"Remarkably, these compounds were never tested directly on the actual target cells – the human neuron", adds lead author Dr. Jerome Mertens of Prof. Brüstle's team, who now works at the Laboratory of Genetics in La Jolla (USA).
This is because, so far, living human neurons have been extremely difficult to obtain. However, with the recent advances in stem cell research it has become possible to derive limitless numbers of brain cells from a small skin biopsy or other adult cell types.
Scientists transform skin cells into nerve cells
Now a research team from the Institute for Reconstructive Neurobiology and the Department of Neurology of the Bonn University Medical Center together with colleagues from the LIFE & BRAIN GmbH and the University of Leuven (Belgium) has obtained such nerve cells from humans. The researchers used skin cells from two patients with a familial form of Alzheimer's Disease to produce so-called induced pluripotent stem cells (iPS cells), by reprogramming the body's cells into a quasi-embryonic stage. They then transformed the resulting so-called "jack-of-all-trades cells" into nerve cells.
Using these human neurons, the scientists tested several compounds in the group of non-steroidal anti-inflammatory drugs. As control, the researchers used nerve cells they had obtained from iPS cells of donors who did not have the disease. Both in the nerve cells obtained from the Alzheimer patients and in the control cells, the NSAIDs that had previously tested positive in the animal models and cell lines typically used for drug screening had practically no effect. The values for the harmful beta-amyloid variants that form the feared aggregates in the brain remained unaffected when the cells were treated with clinically relevant dosages of these compounds.
Metabolic processes in animal models differ from humans
"In order to predict the efficacy of Alzheimer drugs, such tests have to be performed directly on the affected human nerve cells", concludes Prof. Brüstle's colleague Dr. Philipp Koch, who led the study.
Why do NSAIDs decrease the risk of aggregate formation in animal experiments and cell lines but not in human neurons? The scientists explain this with differences in metabolic processes between these different cell types.
"The results are simply not transferable", says Dr. Koch.
The scientists now hope that in the future, testing of potential drugs for the treatment of Alzheimer's disease will be increasingly conducted using neurons obtained from iPS cells of patients.
"The development of a single drug takes an average of ten years", says Prof. Brüstle.
"By using patient-specific nerve cells as a test system, investments by pharmaceutical companies and the tedious search for urgently needed Alzheimer medications could be greatly streamlined".
Source: University of Bonn
Contact: Dr. Oliver Brüstle
APP Processing in Human Pluripotent Stem Cell-Derived Neurons is Resistant to NSAID-Based Gamma-Secretase Modulation
Jerome Mertens, Kathrin Stüber, Patrick Wunderlich, Julia Ladewig, Jaideep C. Kesavan, Rik Vandenberghe, Mathieu Vandenbulcke, Philip van Damme, Jochen Walter, Oliver Brüstle, Philipp Koch
Stem Cell Reports, 05 December 2013, DOI: 10.1016/j.stemcr.2013.10.011
For more on stem cells and cloning, go to CellNEWS at
Thursday, 5 December 2013
Mitochondrial genome of a 400,000-year-old representative of the genus Homo sequenced
Thursday, 05 December 2013
This is a skeleton of a Homo heidelbergensis
from Sima de los Huesos, a unique cave site in
Northern Spain. Credit: Javier Trueba, Madrid
Sima de los Huesos (SH), the "bone pit", is a cave site in Northern Spain that has yielded the world's largest assembly of Middle Pleistocene hominine fossils, consisting of at least 28 skeletons, which have been excavated and pieced together over the course of more than two decades by a Spanish team of palaeontologists led by Juan-Luis Arsuaga. The fossils are classified as Homo heidelbergensis but also carry traits typical of Neanderthals. Until now it had not been possible to study the DNA of these unique hominines.
Matthias Meyer at work in the clean lab.
Credit: Max Planck Institute for
The Sima de los Huesos hominines lived
approximately 400,000 years ago during the
Middle Pleistocene. Credit: Javier Trueba,
Madrid Scientific Films.
"The fact that the mtDNA of the Sima de los Huesos hominine shares a common ancestor with Denisovan rather than Neanderthal mtDNAs is unexpected since its skeletal remains carry Neanderthal-derived features", says Matthias Meyer.
Considering their age and Neanderthal-like features, the Sima hominines were likely related to the population ancestral to both Neanderthals and Denisovans. Another possibility is that gene flow from yet another group of hominines brought the Denisova-like mtDNA into the Sima hominines or their ancestors.
"Our results show that we can now study DNA from human ancestors that are hundreds of thousands of years old. This opens prospects to study the genes of the ancestors of Neanderthals and Denisovans. It is tremendously exciting" says Svante Pääbo, director at the Max Planck Institute for Evolutionary Anthropology.
Prof. Juan Luis Arsuaga, Director of the Centro
Mixto de Evolución and Compòrtamiento
Humanos in Madrid, Spain. Credit: Javier
Trueba, Madrid Scientific Films.
Contact: Dr. Matthias Meyer
A mitochondrial genome sequence of a hominine from Sima de los Huesos
Matthias Meyer, Qiaomei Fu, Ayinuer Aximu-Petri, Isabelle Glocke, Birgit Nickel, Juan-Luis Arsuaga, Ignacio Martínez, Ana Gracia, José María Bermúdez de Castro, Eudald Carbonell and Svante Pääbo
Nature, 4 December 2013, DOI: 10.1038/nature12788
For more on stem cells and cloning, go to CellNEWS athttp://cellnews-blog.blogspot.com/