… you may be carrying a little personal stem cell bank around in your mouth.
September 10, 2010
September 3, 2010
News from the world of stem cell research. This item comes from the United Kingdom, and if the current political climate on the right towards ground-breaking science and medical research holds fast most stem cell news will be coming from anywhere but the United States.
This development does look very promising.
From the link:
In a paper published in the September edition of Nature Materials, a team of Nottingham scientists led by Professor Morgan Alexander in the University’s School of Pharmacy, reveal they have discovered some man-made acrylate polymers which allow stem cells to reproduce while maintaining their pluripotency.
Professor Alexander said: “This is an important breakthrough which could have significant implications for a wide range of stem cell therapies, including cancer, heart failure, muscle damage and a number of neurological disorders such as Parkinson’s and Huntington’s.
“One of these new manmade materials may translate into an automated method of growing pluripotent stem cells which will be able to keep up with demand from emerging therapies that will require cells on an industrial scale, while being both cost-effective and safer for patients.”
September 11, 2009
Snort stem cells instead! Seriously now, this would be quite a therapeutic discovery if it turns into something medically useful.
Snort stem cells to get them to brain
NewScientist Health, Sept. 10, 2009
Snorting stem cells might be a way of getting large numbers of stem cells or therapeutic proteins such as neural growth factor into the brain without surgery, University Hospital of Tübingen researchers have found in an experiment with mice.
August 5, 2009
Via Kurzweil.AI.net— One more benefit of ending the outrageously ridiculous ban on using federal money to research stem cells, DARPA is putting its weight and influence on the subject. This can only be a very good thing for stem cell research.
Military Aims for Instant Repair of Wartime Wounds Wired Danger Room, Aug. 3, 2009
DARPA is asking for a device that can use adult stem cells to regenerate and repair injured body parts, including nerves, bone and skin, using the same (or better) structural and mechanical properties of human tissue.
March 6, 2009
Hallelujah, let the light of basic science shine on.
From the link:
President Obama will announce Monday that he is reversing Bush administration limits on federal financing for embryonic stem cell research as part of a pledge to separate science and politics, White House officials said Friday.
As a presidential candidate, Mr. Obama spoke out in favor of stem cell research, so his intention to undo the curbs put in place by President George W. Bush is not surprising. But the decision is nonetheless of great interest, involving a long-controversial intersection of science and personal moral beliefs.
The officials said that advocates of unfettered stem cell research, as well as about 30 Democratic and Republican lawmakers who support it, had been invited to a White House ceremony scheduled for 11:45 a.m. Eastern time, when Mr. Obama is expected to make an announcement.
One person familiar with planning for the event said the president would also speak about a general return to “sound science” in his administration, as a fulfillment of his campaign promise to draw a demarcation line between politics and science. The Bush administration was often accused of trying to shade, or even suppress, the findings of government scientists on climate change, sex education, contraceptives and other issues, as well as stem cells.
December 15, 2008
Single virus used to convert adult cells to embryonic stem cell-like cells
CAMBRIDGE, Mass. (Dec. 15, 2008) — Whitehead Institute researchers have greatly simplified the creation of so-called induced pluripotent stem (iPS) cells, cutting the number of viruses used in the reprogramming process from four to one. Scientists hope that these embryonic stem-cell-like cells could eventually be used to treat such ailments as Parkinson’s disease and diabetes.
The earliest reprogramming efforts relied on four separate viruses to transfer genes into the cells’ DNA–one virus for each reprogramming gene (Oct4, Sox2, c-Myc and Klf4). Once activated, these genes convert the cells from their adult, differentiated status to an embryonic-like state.
However, this method poses significant risks for potential use in humans. The viruses used in reprogramming are associated with cancer because they may insert DNA anywhere in a cell’s genome, thereby potentially triggering the expression of cancer-causing genes, or oncogenes. For iPS cells to be employed to treat human diseases, researchers must find safe alternatives to reprogramming with such viruses. This latest technique represents a significant advance in the quest to eliminate the potentially harmful viruses.
Bryce Carey, an MIT graduate student working in the lab of Whitehead Member Rudolf Jaenisch, spearheaded the effort by joining in tandem the four reprogramming genes through the use of bits of DNA that code for polymers known as 2A peptides. Working with others in the lab, he then manufactured a so-called polycistronic virus capable of expressing all four reprogramming genes once it is inserted into the genomes of mature mouse and human cells.
When the cells’ protein-creating machinery reads the tandem genes’ DNA, it begins making a protein. However, when it tries to read the 2A peptide DNA that resides between the genes, the machinery momentarily stops, allowing the first gene’s protein to be released. The machinery then moves on to the second gene, creates that gene’s protein, stalls when reaching another piece of 2A peptide DNA, and releases the second gene’s protein. The process continues until the machinery has made the proteins for all four genes.
Using the tandem genes, Carey created iPS cells containing just a single copy of the polycistronic vector instead of multiple integrations of the viruses. This significant advancement indicates that the approach can become even safer if combined with technologies such as gene targeting, which allows a single transgene to be inserted at defined locations.
Interestingly, while Carey’s single-virus method integrates all four genes into the same location, it has proven to be roughly 100 times less efficient than older approaches to reprogramming. This phenomenon remains under investigation.
“We were surprised by the lower efficiency,” Carey says. “We’re not sure why, but we need to look what’s going on with expression levels of the polycistronic virus’s proteins compared to separate viruses’ proteins.”
Although the one virus method is less efficient, Jaenisch maintains it represents an important advance in the field.
“This is an extremely useful tool for studying the mechanisms of reprogramming,” says Jaenisch, who is also a professor of biology at MIT. “Using this one virus creates a single integration in the cells’ DNA, which makes things much easier to handle.”
Written by Nicole Giese
Rudolf Jaenisch’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.
PNAS, online between December 15 and December 19
“Reprogramming of murine and human somatic cells using a single polycistronic vector”
Bryce W. Carey (1,2), Styliani Markoulaki (1), Jacob Hanna (1), Kris Saha (1), Qing Gao (1), Maisam Mitalipova (1), and Rudolf Jaenisch (1,2)
1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
2. Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.
December 7, 2008
The release from today:
Research Explores the Effects of Stem Cell Source and Patient Age on Stem Cell Transplantation Outcomes
SAN FRANCISCO, Dec. 7 /PRNewswire-USNewswire/ — Two studies examining the effects of stem cell source and patient age on stem cell transplantation outcomes will be explored at a press conference taking place on Sunday, December 7, at 8:00 a.m., during the 50th Annual Meeting of the American Society of Hematology in San Francisco, CA. Preliminary results from a study examining a specialized technique for increasing the presence of stem cells in cord blood for transplantation will also be shared during the press conference.
“For years, stem cell transplants have been a standard treatment option for many blood cancers and other hematologic conditions,” said Armand Keating, MD, moderator of the press conference and Director, Division of Hematology, and Professor of Medicine at the University of Toronto, Ontario, Canada. “The results of these studies add to the growing body of knowledge about the best regimens available to help produce durable responses and prolonged survival in many groups of patients.”
Blood cancers – leukemia, lymphoma, and myeloma – are typically treated with a combination of treatments including chemotherapy, biological therapy, radiation therapy, and stem cell transplantation. Stem cell transplantation is the process by which blood stem cells are collected from a donor, or from the patient prior to chemotherapy, and then infused into the patient after treatment. The transplanted stem cells travel to the bone marrow and begin to produce new blood cells, replacing those that are destroyed as a side effect of chemotherapy. Stem cell transplants are categorized by the source of the stem cells (bone marrow, peripheral blood, or cord blood) and by their origin – autologous (from the patient) or allogeneic (from a donor).
Effect of Stem Cell Source on Transplant Outcomes in Adults With Acute Leukemia: A Comparison of Unrelated Bone Marrow, Peripheral Blood, and Cord Blood [Abstract #151]
Mary Eapen, MBBS, the Center for International Blood and Marrow Transplantation along with the European Group for Blood and Marrow Transplantation and the New York Blood Center
In the absence of a matched sibling donor, the first choice for stem cell transplantation for patients with acute leukemia is an unrelated adult donor whose tissue type matches that of the patient. However, when such a donor is not available, the researchers of this study found that mismatched unrelated cord blood transplants were a suitable alternative to mismatched bone marrow or peripheral blood transplants because cord blood is readily available, making it an ideal option when transplantation is needed urgently.
For successful transplantation, bone marrow and peripheral blood donors are examined for genetic compatibility with the patient by comparing their human leukocyte antigens (HLAs). Current estimates from the National Marrow Donor Program donor registry suggest that the probability of finding a matched unrelated adult donor is relatively low (51 percent for Caucasians, 30 percent for Hispanics, 20 percent for Asians, and 17 percent for African Americans).
Cord blood donated to public cord blood banks can be an alternative source of stem cells for patients who need a transplant but cannot find a matched adult donor. The matching requirements for cord blood are not as strict as for bone marrow or peripheral blood because cord blood cells are immunologically immature and therefore more tolerant to mismatching.
The purpose of this study was to determine the efficacy of three types of stem cell sources: bone marrow, peripheral blood, and cord blood. Study results were based on an analysis of the outcomes of 1,240 adults with acute leukemia (707 patients with acute myeloid leukemia and 533 patients with acute lymphocytic leukemia) from 2002 to 2006. Of those patients who received a bone marrow stem cell transplant, 243 were matched at eight out of eight possible HLA loci and 111 were matched at seven HLA loci. In those receiving a peripheral blood stem cell transplant, 518 were matched at eight HLA loci and 210 at seven HLA loci. In those receiving cord blood transplants, 28 were matched at five or six HLA loci and 110 matched at four HLA loci.
The study found that there were fewer transplant-related deaths for matched peripheral blood and bone marrow transplants (27 percent and 26 percent, respectively) than as for mismatched peripheral blood, bone marrow, and cord blood transplants (42 percent, 37 percent, and 41 percent, respectively). Leukemia-free survival (LFS) and overall survival (OS) were highest after transplantation of matched peripheral blood (LFS: 43 percent; OS: 45 percent) and bone marrow (LFS: 46 percent; OS: 48 percent). These rates were lower after transplantation of mismatched peripheral blood (LFS: 33 percent; OS: 36 percent), bone marrow (LFS: 34 percent; OS: 38 percent), and cord blood (LFS: 33 percent; OS: 35 percent). Importantly, rates of transplant-related deaths, leukemia-free survival, and overall survival for the three types of mismatched transplants were similar even though cord blood transplants were mismatched at more HLA loci.
Notch-Mediated Expansion of Human Cord Blood Progenitor Cells Results in Rapid Myeloid Reconstitution in Vivo Following Myeloablative Cord Blood Transplantation
Colleen Delaney, MD, Fred Hutchinson Cancer Research Center, Seattle, WA
This phase I study found that cord blood that is cultured to increase the number of CD34+ stem cells prior to transplantation helped to decrease the time to engraftment in patients with acute myeloid leukemia.
Cord blood is a valuable source of hematopoietic stem cells as it has a higher concentration of these cells than is normally found in adult blood. However, as only a small quantity of blood can typically be obtained from an umbilical cord, resulting in fewer available stem cells for transplantation, researchers have been investigating novel methods to expand the number of stem cells available from cord blood to help increase the success rates of cord blood stem cell transplants.
The objective of this study is to evaluate the safety and potential efficacy of giving increased numbers of cord blood progenitor cells that have been generated through a novel methodology whereby CD34+ cord blood progenitor cells are cultured prior to infusion to rapidly multiply in order to decrease the time required for the transplanted cells to engraft and begin production of healthy blood cells.
A total of six patients with acute myeloid leukemia were treated with a transplantation- preparation regimen of cytoxan (120 mg/kg), fludarabine (75 mg/m^2), and TBI (1320 cGy), followed one day later by an infusion of one unit of non-cultured cord blood and one unit of cord blood that had been CD34+ enriched and cultured for 16 days. The non-cultured unit was given to provide long-term repopulating stem cells that had not been previously manipulated, while the goal of the expanded unit was to provide cells capable of rapid myeloid recovery.
To achieve best results, cord blood units that most closely genetically matched the patient were selected for transfusion. All non-cultured cord blood stem cells were matched for four out of six alleles for each patient. For the cultured cord blood cells, two patients received a five-out-of-six allele match and four patients received a four-out-of-six allele match. There was an average CD34+ increase of 160 (range 41 to 382), meaning that for every one CD34+ cell, there were 160 CD34+ cells after the culture, with an average total nucleated cell fold increase of 660 (range 146 to 1496). A control group of 17 patients underwent an identical transplant regimen, but received two non-cultured cord blood units.
A relatively rapid engraftment time, averaging 14 days, was observed in the six patients in the experimental group compared with 25 days for the patients in the control group. The contribution of the expanded and non-cultured cord blood cells was determined by a DNA-based assay beginning seven days following the transplant. In the five patients with early engraftment, the engrafted cells present at day seven were derived almost entirely from the cultured unit. Persistent contribution to engraftment from the cultured cells was noted in two patients. One patient had persistent contribution from the cultured cells through 280 days post-transplant that was no longer noticeable at one year, and the second patient continued to demonstrate contribution from the cultured cells at 180 days post-transplant. One patient died on day 462 from a rare complication of myelitis (inflammation of the spinal cord) caused by the varicella-zoster virus, while all other patients were still in remission.
Non-Myeloablative Hematopoietic Stem Cell Transplantation in Older Patients With AML and MDS: Results From the Center for International Blood and Marrow Transplant Research (CIBMTR) [Abstract #346]
Sergio Giralt, MD, The University of Texas M. D. Anderson Cancer Center, Houston, TX
This study found that the outcomes of adults over the age of 65 undergoing allogeneic stem cell transplantation for the treatment of acute myeloid leukemia and myelodysplastic syndromes were similar to younger adults even after adjusting for multiple risk factors. The researchers concluded that age alone should not be a limiting factor for proceeding to allogeneic stem cell transplantation in these patients.
While stem cell transplantation remains one of the best treatment options for increasing overall survival and a possible cure for patients with acute myeloid leukemia and myelodysplastic syndromes, transplants generally are not given to patients over the age of 65 because of concerns about extreme toxicity and poor outcomes. Over the past few years, non-myeloablative transplants that require smaller and safer doses of chemotherapy and radiation have allowed stem cell transplants to be conducted in older individuals or other patients considered too weak to withstand conventional stem cell treatment regimens.
To better study age as a predictor of outcome in patients receiving stem cell transplants, data from the Center for International Blood and Marrow Transplant Research (CIBMTR) on 565 patients with acute myeloid leukemia and 551 patients with myelodysplastic syndromes were retrospectively analyzed for transplant-related mortality, engraftment, incidence of acute and chronic graft-versus-host disease, leukemia-free survival, and overall survival. Outcome data gathered from 1995 to 2005 were stratified into four groups by patient age for comparison: ages 40 to 54, 54 to 59, 60 to 64, and 65 and older.
The analysis found that there was no statistically significant difference in transplant-related mortality across age groups, and no overall difference in the occurrence of acute graft-versus-host disease (31-35 percent at 100 days) or chronic graft-versus-host disease (36-53 percent at two years). Rates of relapse were similar across all age groups (29-30 percent at three years). Additionally, no statistically significant impact of age was found for transplant-related mortality, leukemia-free survival, or overall survival. Type of disease and disease status at transplant were significant risk factors for leukemia-free survival and overall survival at one year and for transplant-related mortality and relapse at two years. Patients’ general health and degree of tissue-type match between recipient and donor were also significant at two years for nearly all outcomes.
American Society of Hematology 50th Annual Meeting
The study authors and press program moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on combating blood clots, therapeutic strategies for platelet disorders, treatment advances in leukemia and lymphoma, and advances in screening and treatment for sickle cell disease.
The American Society of Hematology (www.hematology.org) is the world’s largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology. In September, ASH launched Blood: The Vital Connection (www.bloodthevitalconnection.org), a credible online resource addressing bleeding and clotting disorders, anemia, and cancer. It provides hematologist-approved information about these common blood conditions including risk factors, preventive measures, and treatment options. A cornerstone of this public awareness campaign is a new documentary by award-winning filmmaker Joseph Lovett called “Blood Detectives,” which will air on the Discovery Health cable network on December 19, 2008, at 7:00 p.m. ET/PT and again at 12:00 midnight. The show focuses on hematologists as they work to unravel medical mysteries and save lives.
Source: American Society of Hematology
Web Site: http://www.bloodthevitalconnection.org/
December 5, 2008
Dormant stem cells for emergencies
Many specialized cells, such as in the skin, intestinal mucosa or blood, have a lifespan of only a few days. For these tissues to function, a steady replenishment of specialized cells is indispensable. This is the task of so-called “adult” stem cells also known as tissue stem cells.
Stem cells have two main characteristics: First, they are able to differentiate into all the different cell types that make up their respective tissue – a property called pluripotency. Second, they need to renew themselves in order to be able to supply new specialized tissue cells throughout life. These processes have best been studied in mouse bone marrow.
Up to now, scientists have assumed that adult stem cells have a low division rate. According to theory, they thus protect their DNA from mutations, which happen particularly during cell division and can lead to transformation into tumor stem cells. However, the actual number of divisions of a blood stem cell throughout an organism’s lifespan has remained unknown.
Professor Dr. Andreas Trumpp and Dr. Anne Wilson have now discovered a group of stem cells in mouse bone marrow that remain in a kind of dormancy almost throughout life. Trumpp, who has been head of the Cell Biology Division at DKFZ since summer 2008, had carried out these studies at the Ecole Polytechnique Fédérale in Lausanne, Switzerland, jointly with colleagues at the Ludwig Institute for Cancer Research located in the same city.
The scientists labeled the genetic material of all mouse blood cells and subsequently investigated how long this label is retained. With each division, the genetic material is apportioned to the daughter cells and, thus, the labeling dilutes. During these studies, the investigators discovered the dormant stem cells which divide only about five times throughout the life of a mouse. Translated to humans, this would correspond to only one cell division in 18 years. Most of the time, these cells, which constitute no more than about 15 percent of the whole stem cell population, remain in a kind of dormancy with very low metabolism. In contrast, stem cells of the larger group, the “active” stem cells, divide continuously about once a month.
However, in an emergency such as an injury of the bone marrow or if the messenger substance G-CSF is released, the dormant cell population awakes. Once awakened, it shows the highest potential for self-renewal ever to be observed in stem cells. If transplanted into irradiated mice, these cells replace the destroyed bone marrow and restore the whole hematopoietic system. It is possible to isolate new dormant stem cells from the transplanted animals and these cells are able to replace bone marrow again – this can be done several times in a row. The situation is different with “active” stem cells, where bone marrow replacement can successfully be carried out only once.
“We believe that the sleeping stem cells play almost no role in a healthy organism,” Trumpp explains. “The body keeps its most potent stem cells as a secret reserve for emergencies and hides them in caves in the bone marrow, also called niches. If the bone marrow is damaged, they immediately start dividing daily, because new blood cells are needed quickly.” Once the original cell count is restored and the bone marrow is repaired, these stem cells go back to deep sleep. The larger population of “active” stem cells, however, keeps up the physiological balance of blood cells in the normal healthy state.
Andreas Trumpp expects that these results may give valuable impetus to our understanding of cancer stem cells: “Cancer stem cells, too, probably remain in a dormant state most of the time – we think that this is one of the reasons why they are resistant to many kinds of chemotherapy that target rapidly growing cells. If we were able to wake up these sleepers before a patient receives treatment, it might be possible to also eliminate cancer stem cells for the first time and, thus, to treat the disease much more effectively by destroying the supply basis.”
In a second article*, Dr. Elisa Laurenti from Trumpp’s team shows that the two cancer genes c-Myc and N-Myc play a vital role in the functioning of stem cells. The two genes provide the blueprints for what are called transcription factors, which in turn regulate the activity of other genes and are overactive particularly in cancer cells. If both c-Myc and N-Myc are switched off at the same time in mice, the animals quickly start suffering from a general lack of blood cells and quickly die.
The two genes are not only responsible for survival of nearly all blood cells, but they also jointly control the two prime characteristics of stem cells – the capability of self-renewal and the potential to produce differentiated blood cells. This result is not only relevant for our understanding of stem cells, but it also explains the damage that can be caused by overactive Myc genes. Trumpp explains: “In tumors, too, c-Myc and N-Myc are presumably responsible for the self-renewal of cancer stem cells and, thus, for uncontrolled growth.”
Anne Wilson; Gabriela Oser; Richard van der Wath; William Blanco; Elisa Laurenti; Maike Jaworski; Cyrille Durant; Leonid Eshkind; Ernesto Bockamp; Pietro Lio; Robson MacDonald, and Andreas Trumpp: Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. CELL 2008, DOI 10.1016/j.cell.2008.10.048
*Elisa Laurenti, Barbara Varnum-Finney, Anne Wilson, Isabel Ferrero, William E. Blanco-Bose, Armin Ehninger, Paul S. Knoepfler, Pei-Feng Cheng, H. Robson MacDonald, Robert N. Eisenman, Irwin D. Bernstein, and Andreas Trumpp: Hematopoietic Stem Cell Function and Survival Depend on c-Myc and N-Myc Activity. CELL Stem Cell 2008, DOI 10.1016/j.stem.2008.09.005
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is the largest biomedical research institute in Germany and is a member of the Helmholtz Association of National Research Centers. More than 2,000 staff members, including 850 scientists, are investigating the mechanisms of cancer and are working to identify cancer risk factors. They provide the foundations for developing novel approaches in the prevention, diagnosis , and treatment of cancer. In addition, the staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. The Center is funded by the German Federal Ministry of Education and Research (90%) and the State of Baden-Württemberg (10%).
November 6, 2008
From the release:
New advancements in the use of adult, embryonic stem cells for tissue regeneration
Indianapolis, Ind. – November 06, 2008 – A major issue in the development of regenerative medicine is the cell sources used to rebuild damaged tissues. In a review of the issue published in Developmental Dynamics, researchers state that inducing regeneration in humans from the body’s own tissues by chemical means is feasible, though many questions must be answered before the process can reach clinical status.
Regeneration is a regulative developmental process ubiquitous across all species. It functions throughout the life cycle to maintain or restore the normal form and function of cells, tissues and, in some cases organs, appendages and whole organisms. The roots, stems and leaves of plants, for example, have extensive regenerative capacity, and entire plants can grow from single cells or small cuttings.
The regenerative capability of most vertebrate animals, however, is restricted to certain tissues. In the absence of injury, many cell types such as epithelia and blood cells turn over rapidly, while others such as hepatocytes, myofibers, osteocytes, and most neurons, have low turnover rates or do not turn over at all. In organisms that grow throughout life, such as fish, the total number of cells in various tissues increases continuously, indicating that the number of new cells produced is higher than the number of cells lost.
By contrast, the loss of normal tissue mass and/or architecture to acute injury or disease in humans requires a more intense and qualitatively different regenerative response that restores the tissue to its original state. This response is called injury-induced regeneration.
A major issue for cell transplant therapies is the source of the cells to be used. Three sources of cells can be tapped for transplant: differentiated tissues, adult stem cells (ASCs) and derivatives of embryonic stem cells (ESCs). Adult stem cells regenerate epithelia, brain tissue, muscle, blood and bone. They have also been found in other tissues that normally scar after injury, such as myocardium, spinal cord and retina tissues.
“Adult stem cell therapy has real potential to regenerate at least muscle and bone damaged by injury or genetic disease, and cardiac stem cells may be a way to regenerate new cardiomyocytes after myocardial infarction,” says David L. Stocum, co-author of the paper.
Progress is also being made toward the use of ESCs to derive functional cells for treatment of diabetes and muscular dystrophy.
A procedure has been developed to direct the differentiation of human ESCs to pancreatic islet cells, including insulin producing cells. When implanted into mice, the cells produce human insulin in response to glucose stimulation and protect against hyperglycemia.
“ESCs show great promise as a cell source for the regeneration of new tissue, due to their high growth and self-renewal capacity, and their ability to differentiate into a myriad of precursor or differentiated cell types when directed by the appropriate set of environmental factors,” says co-author Günther K.H. Zupanc.
The recently acquired ability to reprogram adult somatic cells to ESCs in culture (“induced pluripotent stem cells”) has solved bioethical concerns surrounding the destruction of somatic cell nuclear transfer embryos to make personal embryonic stem cells that will not be immunorejected. The authors state, however, that induced pluripotent stem cells raise their own biological and bioethical issues. Biological issues include the differentiation and survival time of reprogrammed somatic cells, and the need to develop methods to reprogram cells without introducing exogenous DNA. Ethical issues, including cost, the ease of reprogramming for the purpose of conducting unethical experiments, like the derivation of human offspring, have yet to be resolved.
The ability to reprogram adult somatic cells to ESCs in culture has led the authors to the concept that it may be possible to use natural or synthetic molecules to reprogram adult somatic cells in vivo to adult stem cells that will recapitulate the development of a tissue, organ or appendage, or to stimulate resident adult stem cells to do so. They argue that strong regenerators, such as fish and amphibians know how to do this naturally, and should be studied to learn what molecules are required for such stimulation or reprogramming. The counterparts of these molecules, or synthetic small molecules that mimic their action, could then be applied to regeneration-deficient mammalian tissues.
July 24, 2008
This press release from the University of California at Irvine covers a new potential brain injury cure using adult stem cells in the brain.
Adult stem cells activated in mammalian brain
Locating cell origin provides foundation for brain injury cure
Irvine, Calif., July 24, 2008
Adult stem cells originate in a different part of the brain than is commonly believed, and with proper stimulation they can produce new brain cells to replace those lost to disease or injury, a study by UC Irvine scientists has shown.
Evidence strongly shows that the true stem cells in the mammalian brain are the ependymal cells that line the ventricles in the brain and spinal cord, rather than cells in the subventricular zone as biologists previously believed. Brain ventricles are hollow chambers filled with fluid that supports brain tissue, and a layer of ependymal cells lines these ventricles.
Knowing the cell source is crucial when developing stem cell-based therapies. Additionally, knowing that these normally dormant cells can be coaxed into dividing lays the groundwork for future therapies in which a patient’s own stem cells produce new brain cells to treat neurological disorders and injuries such as Parkinson’s disease, stroke or traumatic brain injury.
“With such a therapy, we would know which cells in the body to target for activation, and their offspring would have all the properties necessary to replace damaged or missing cells,” said Darius Gleason, lead author of the study and a graduate student in the Department of Developmental and Cell Biology. “It is a very promising approach to stem cell therapy.”
Study results appear this month online in the journal Neuroscience.
Stem cells are the “master cells” that produce each of the specialized cells within the human body. If researchers could control the production and differentiation of stem cells, they may be able to use them to replace damaged tissues.
One focus of stem cell research is transplantation, which entails injecting into the body healthy cells that may or may not genetically match the patient. Transplantation of nonmatching stem cells requires the use of drugs to prevent the body from rejecting the treatment.
But, working with a patient’s own cells would eliminate the need for transplantation and immunosuppressant drugs and may be a better alternative, scientists say. Ependymal cells line the fluid-filled ventricles, so a drug to activate the cells could theoretically travel through this fluid directly to the stem cells.
“The cells already match your brain completely since they have the same genetic make-up. That is a huge advantage over any other approach that uses cells from a donor,” Gleason said. “If they are your cells, then all we are doing is helping your body fix itself. We’re not reinventing the repair process.”
In this study, Gleason and Peter Bryant, developmental and cell biology professor, used rats treated to develop the animal equivalent of Parkinson’s disease. They chose this type of rat because in a previous study by UCI collaborator James Fallon, a small protein given to the brain-damaged rats sparked a rapid and massive production and migration of new cells, and significantly improved motor behavior.
First, the UCI researchers sought to determine the true location of stem cells in the rats by looking for polarized cells, which have different sets of proteins on opposite sides so that when one divides it can produce two different products. Polarization gives rise to asymmetric cell division, which produces one copy of the parent and a second cell that is programmed to turn into another cell type. Asymmetric cell division is the defining characteristic of a stem cell.
On rat brain samples, the researchers applied antibodies to identify proteins that may be involved in asymmetric cell division, and they found that polarization exists on the ependymal cells. “It couldn’t have been a stronger signal or clearer message. We could see that the only cells undergoing asymmetric cell division were the ependymal cells,” Gleason said.
Next, they gave a drug to induce cell division in the rats and examined their brains at intervals ranging from one to 28 days after the treatment. At each interval, they counted cells that were dividing in the ependymal layer. They found the most division at 28 days, when about one-quarter of the ependymal cells were dividing. Previous studies by researchers at other institutions were successful in getting only a few cells to divide in that layer.
“One interpretation of previous studies is there are scattered stem cells in the ependymal layer, and it is hard to locate them,” Bryant said. “But we believe that all of the ependymal cells are stem cells, and that they all have the ability to be activated.”
Researchers don’t know yet what sparks cell division at the molecular level, but learning that process and how to control it could lead to a safe, effective stem cell therapy.
Fallon, psychiatry and human behavior professor, and researchers Magda Guerra and Jian-Chang Liu contributed to this study. All of the scientists are affiliated with the UCI Sue and Bill Gross Stem Cell Research Center.
Gleason’s work is supported by a stem cell training grant from the California Institute for Regenerative Medicine. The UCI Office of Research, the Optical Biology Core in the Developmental Biology Center, a gift from the Joseph’s Foundation, and the UC MEXUS-CONACYT Postdoctoral Research Program also supported this study.
About the University of California, Irvine: The University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 27,000 undergraduate and graduate students and nearly 2,000 faculty members. The third-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3.6 billion. For more UCI news, visit www.today.uci.edu.
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July 11, 2008
Here’s a more traditional (for this blog) posting from KurzweilAI.net — a stem cell breakthrough, solar energy harvesting breakthrough, and another breakthrough (see a theme here) in hard drive capacity.
New Technique Harvests Stem Cells at Earlier Stage HealthDay News, July 9, 2008
Researchers at Vrije Universiteit Brussel have derived human embryonic stem cells (hESC) earlier in the development stage of a blastomere (when it only has four cells), so the whole embryo is not destroyed.
Previously, scientists were able to derive hESC lines at the 8-cell stage, but that methodhad variable success rates and required the cells to be cultured with established hESCs. The new method doesn’t require a co-culture.
The development could make stem cell researcheasier to conduct by not raising as many ethical concerns. It could also change pre-implantation genetic diagnosis (PGD), by enabling the biopsy of one cell from a 4-cell stage embryo. This would let the remaining three cells grow into a blastocyst (five-day embryo) that could be implanted into the uterus and develop into a healthy baby. Currently GPD is performed at the 8-cell stage.
Organic dye lets window panes harvest the Sun New Scientist news service, July 10, 2008
Exotic organic dyes are coated onto an ordinary sheet of glass, trapping light inside the glass and allowing it to be channelled to photovoltaic cells placed along the edges of the sheet. The dyes can absorb light across the visible spectrum and emit it at the longer frequencies needed for optimal conversion.
Seagate’s Latest Desktop HDD Has 1.5TB Capacity Hot Hardware, July 10, 2008
Seagate announced Thursday three new consumer-level hard drives today, which it claims are the “industry’s first 1.5-terabyte desktop and half-terabyte notebook hard drives.”
May 19, 2008
Methuselah Foundation Announces Aging 2008 at UCLA KurzweilAI.net, May 19, 2008
On Friday June 27th, leading scientists and thinkers in stem cell research and regenerative medicine will gather in Los Angeles at UCLA for Aging 2008 to explain how their work can combat human aging, and the sociological implications of developing rejuvenation therapies.
Aging 2008 is free, with advance registration required.
Dr. Aubrey de Grey, chairman and chief science officer of the Methuselah Foundation, said “Our organization has raised over $10 million to crack open the logjams in longevity science. With the two-armed strategy of direct investments into key research projects, and a competitive prize to spur on scientists racing to break rejuvenation and longevity records in lab mice, the Foundation is actively accelerating the drive toward a future free of age-related degeneration.”
The speakers at Aging 2008 will argue that the near-term consequences of intense research into regenerative medicine could be the development of therapies that extend healthy human life by decades, even if the therapies are applied in middle age. Peter Thiel, president of Clarium Capital, initial investor in Facebook, and lead sponsor of Aging 2008, said, “The time has come to challenge the inevitability of aging. This forum will provide an excellent opportunity to look at the scientific barriers that must be overcome to substantially extend healthy human life, as well as the ethical implications of doing so.”
Aging 2008 also serves as the free opening session for the technically focused Understanding Aging Conference, which will run at UCLA on June 28th and 29th.
What: Aging: The Disease, The Cure, The Implications, hosted by Methuselah Foundation
When: Friday, June 27, 2008, Drinks 4pm, Presentations 5pm, Dinner 8pm
Where: Royce Hall, 405 Hilgard Ave, Los Angeles, CA 90024
* Dr. Bruce Ames, Professor of Biochemistry and Molecular Biology at UC Berkeley
* G. Steven Burrill, Chairman of Pharmasset and Chairman of Campaign for Medical Research
* Dr. Aubrey de Grey, Chairman and CSO of Methuselah Foundation and author of Ending Aging
* Dr. William Haseltine, Chairman of Haseltine Global Health
* Daniel Perry, Executive Director of Alliance for Aging Research
* Bernard Siegel, Executive Director of Genetics Policy Institute
* Dr. Gregory Stock, Director of Program on Medicine, Technology & Society at UCLA School of Medicine
* Dr. Michael West, CEO of BioTime and Adjunct Professor of Bioengineering at UC Berkeley
About Methuselah Foundation
The Methuselah Foundation is a 501(c)(3) nonprofit organization dedicated to extending the healthy human lifespan. Founded in 2002 by entrepreneur David Gobel and gerontologist Dr. Aubrey de Grey, the Methuselah Foundation funds two major projects: The Mprize, a multimillion dollar research prize, and SENS, a detailed engineering plan to repair aging-related damage. Learn more at http://mfoundation.org.
April 16, 2008
Nice roundup from KurzweilAI.net today.
First up is nngews on a more accurate method for creating movies of molecular and biological processes.
Keeping with the biology theme is a breakthrough for treating heart damage with stem cells.
Finishing the group is a bit about progress toward a quantum computer.
Movies of biological and chemical molecules made for first time KurzweilAI.net, April 16, 2008Argonne National Laboratory scientists have developed accurate techniques for making movies of actual biological and chemical molecules for the first time.
Using the high-intensity X-rays at the Advanced Photon Source, the scientists have measured images that are blurred by these motions and used computer processing algorithms to create more accurate movies of the molecular motions.
Molecule prompts blood stem cells to help repair heart damage in animal model PhysOrg.com, April 15, 2008University of Texas Southwestern Medical Center researchers used drug-treated blood stem cells to repair heart damage in an animal model.
They screened about 147,000 molecules to find one that could transform human blood stem cells into a form resembling immature heart cells. When they implanted blood stem cells activated by this compound into injured rodent hearts, the human cells took root and improved the animals’ heart function.
Toward a Quantum Internet Technology Review, April 15, 2008Northwestern University researchers have build a quantum logic gate–a fundamental component of a quantum computer–within an optical fiber, using entangled photon pairs.
The gate could be part of a circuit that relays information securely, over hundreds of kilometers of fiber, from one quantum computer to another. It could also be used on its own to find solutions to complicated mathematical problems.
April 14, 2008
Can micro-scaffolding help stem cells rebuild the brain after stroke? KurzweilAI.net, April 13, 2008Neural stem cell-scaffold combinations could be injected into the brain to provide a framework inside the cavities caused by stroke so that the cells are held there until they can work their way to connect with surrounding healthy tissue, University of Nottingham neurobiologists propose.