The Government has agreed to back down on strict laws planned for embryonic stem-cell experiments after a “compelling case” was made by leading scientists in a letter to The Times.
The letter, published last week, expressed alarm that the Human Fertilisation and Embryology Bill would delay potentially life-saving research by requiring all tissue used to create cloned embryonic stem cells to have the explicit consent of its donor.
The Bill, which is passing through Parliament, was set to outlaw access to most of the tissue banks that act as vast libraries of the genes that contribute to serious disorders.
More than 50 biomedical researchers and administrators, including four Nobel prizewinners, have told ministers that such strict measures would deny stem-cell scientists the use of tissue banks for studying diseases such as muscular dystrophy, Parkinson’s and diabetes.
Picture From:http://www.telegraph.co.uk
The tissue banks enable scientists to create cloned embryos that can be implanted with the genetic material of patients, assisting research into how the illnesses develop.
The Government’s justification for requiring “express consent” had been that some patients who agreed to donate cells may not have realised that their tissue could later be used for cloning. The letter in The Times said that the requirement jeopardised years of expensive research and the cultivation of unique tissue samples as raw material for cloning.
As tissue was collected before it became possible to clone embryos in this way, the scientists argued that it would have been impossible for anonymous donors to give permission for their DNA to be used in embryonic stem-cell models of diseases. Signatories included the Nobel medicine laureates Sir Martin Evans, Sir Paul Nurse, Sir John Sulston and Sir Tim Hunt, as well as leading stem-cell experts such as Sir Ian Wilmut, Dame Julia Polak and Professor Stephen Minger.
The Government is also considering changing a second measure in the Bill, which will further limit stem-cell research by blocking the use of any tissue from children even if their parents gave consent.
Ministers were reluctant to consider any changes to the Bill, but after a debate in the House of Lords last Tuesday the Department of Health conceded the need to allow exceptions.
In a letter sent this week to peers who took part in the debate in the Lords, the department concedes: “A compelling case has been made that the requirement for express consent could, in certain circumstances, impose a significant burden in this field.”
Evan Harris, the Liberal Democrat MP who organised the letter to The Times, said yesterday: “Plaudits to the scientists for speaking out and the Government for listening.”
The Bill is due to enter the Commons in the spring.
Article From:http://www.timesonline.co.uk/tol/news/uk/science/article3292055.ece
Embryonic stem cells treated with growth factor reverse hemophilia in mice
Mouse embryonic stem cells treated in culture with a growth factor and then injected into the liver reverse a form of hemophilia in mice analogous to hemophilia B in humans, the new study shows. A report of the study appears in the journal Proceedings of the National Academy of Sciences today (Feb. 15).
The genetically altered mice lack the clotting substance factor IX, which in humans results in the hereditary bleeding disorder known as hemophilia B. This disease, much less common than hemophilia A, affects roughly one of every 35,000 people, primarily males.
Although embryonic stem, or ES, cells can differentiate into most cell types in the body, numerous problems have arisen in translating their potential into therapeutic strategies, the UNC School of Medicine study authors reported.
These problems include poor engraftment, limited function, rejection of engrafted cells by the immune system and teratomas, tumors involving a mixture of tissue not normally found at that site.
The new study used a line of mouse ES cells developed in the laboratory of senior co-author Dr. Oliver Smithies, Excellence professor of pathology and laboratory medicine at UNC.
A member of the National Academy of Sciences, Smithies has won many honors for gene targeting, a technique he pioneered. This technique allows for the development of mice with specific genetic mutations that mimic human illnesses such as hemophilia. In 2001, Smithies received the Albert Lasker Award for Basic Medical Research, often called "America's Nobel."
In the study, ES cells were treated with fibroblast growth factor for seven days prior to injection. As expected, this resulted in ES cells differentiating into early endoderm like precursors, which the researchers named "putative endoderm precursors," or PEPs. Endoderm refers to the inner layer of early embryonic cells that develops into the digestive and respiratory systems.
"Not only do ES cells differentiate into PEPs, they also engraft, persist, differentiate further and then function following injection, resulting in the persistent production of factor IX protein that can only come from a hepatocyte (liver cell) and hemophilia reversal," said study lead author Dr. Jeffrey H. Fair, associate professor of surgery and division chief of abdominal transplant surgery.
Moreover, he said, the PEP cells robustly engraft within the liver and were not recognized by the immune system as foreign.
"Within a few weeks, PEPs became hepatocytes," Fair added. "They went from something that is a very early grandparent of the hepatocyte to becoming hepatocytes. After 115 days, nearly four months after injection, mice still produced factor IX without immune suppression. This occurred even in mice that were a complete immunologic tissue mismatch to the PEPs. In addition, the incidence of teratomas was low."
The researchers believe this study demonstrates the power of multidisciplinary collaboration, said co-lead author Dr. Bruce A. Cairns, assistant professor of surgery and director of research in the N.C. Jaycee Burn Center. "This approach may not only be beneficial, but required in order to solve complex problems such as these in medicine."
Although a number of questions need to be answered, this work has great potential for future applications, not only as a novel therapeutic possibility for hemophilia but also for other genetic or acquired diseases of the liver, said senior co-author Dr. Jeffery A. Frelinger, Kenan professor and chairman of microbiology and immunology.
"The data published in this study shows that embryonic stem cells partially differentiated, are able to remain in the liver and be functional without apparent immunological rejection. This transforms them into possible candidates for cellular transplantation into the liver."
Along with Fair, Cairns, Smithies and Frelinger, co-authors from the department of surgery are Dr. Michael A. LaPaglia, Dr. Montserrat Caballero, Dr. Anthony A. Meyer (chairman) and W. Andrew Pleasant. From the department of pathology and laboratory medicine are Drs. Seigo Hatada and Hyung-suk Kim. From the College of Arts and Sciences' department of biology are Drs. Tong Gui and Darrel W. Stafford; and from the department of genetics, Dr. Larysa Pevny.
The research was supported by grants from the National Institutes of Health and the N.C. Jaycee Burn Center.
Study adds to evidence of adult stem cells' promising therapeutic role
BURLINGTON, VT (USA) - For the first time, researchers have demonstrated that adult human stem cell transplantation results in spontaneous cell regeneration in damaged lung tissue.
Published in the August 1 issue of the American Journal of Respiratory and Critical Care Medicine, the study further supports an existing body of research that suggests blood- and marrow-derived stem cells have the capacity to become many different human tissues.
'Many of the body's tissues once thought to be only locally regenerative may, in fact, be actively replaced by circulating stem cells after hematopoietic or blood-forming stem cell transplantation,' says lead author Benjamin Suratt, M.D., assistant professor of medicine and Vermont Lung Center researcher at the University of Vermont College of Medicine.
'This finding is of note not only for its novelty as a regenerative mechanism of the lung, but also for its vast therapeutic implications for any number of lung diseases.'
According to Suratt, the study's findings indicate that circulating stem cells are going into organ tissue and repairing damage, which could have a huge impact on the treatment of such devastating lung diseases as emphysema or cystic fibrosis.
Supported by funding from the National Institutes of Health and a National Center for Research Resources Centers for Biomedical Research Excellence grant, Suratt and his colleagues are currently looking further into what types of cells have the capacity to differentiate and generate a different type of cell, and whether these cells might be used to treat cystic fibrosis.
For more information on research taking place at the Vermont Lung Center at the University of Vermont, go to www.vermontlung.org
To link to the article abstract, go to:
ajrccm.atsjournals.org/cgi/content/abstract/168/3/318
Embryonic stem cells.
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos [6]. A blastocyst is an early stage embryo - approximately 4 to 5 days old in humans and consisting of 50-150 cells. ES cells are pluripotent, and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta. Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[7]
Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEF's) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[8] Without optimal culture conditions or genetic manipulation[9] embryonic stem cells will rapidly differentiate. A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network which ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[10] The cell surface proteins most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81.
The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[11] After 20 years of research, there are no approved treatments or human trials using embryonic stem cells. Their tendency to produce tumors and malignant carcinomas, cause transplant rejection, and form the wrong kinds of cells are just a few of the hurdles that embryonic stem cell researchers still face.[12] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placentaStem cell properties Defining properties
The rigorous definition of a stem cell requires that it possesses two properties:
* Self-renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
* Unlimited potency - the capacity to differentiate into any mature cell type. In a strict sense, this requires stem cells to be either totipotent or pluripotent, although some multipotent and/or unipotent progenitor cells are sometimes referred to as stem cells.
These properties can be illustrated in vitro, using methods such as clonogenic assays, where the progeny of single cell is characterized.[4][5] However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. Considerable debate exists whether some proposed adult cell populations are truly stem cells.
Potency definitions
Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
Pluripotent, embryonic stem cells originate as inner mass cells with in a blastocyst. The stem cells can become any tissue in the body, excluding a placenta. Only the morula's cells are totipotent, able to become all tissues and a placenta.
Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.
* Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can differentiate into embryonic and extraembryonic cell types.
* Pluripotent stem cells are the descendants of totipotent cells and can differentiate into cells derived from any of the three germ layers.
* Multipotent stem cells can produce only cells of a closely related family of cells (e.g. hematopoietic stem cells differentiate into red blood cells, white blood cells, platelets, etc.).
* Unipotent cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells.
Embryonic stem cells
Main article: Embryonic stem cell
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos [6]. A blastocyst is an early stage embryo - approximately 4 to 5 days old in humans and consisting of 50-150 cells. ES cells are pluripotent, and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia Inhibitory Factor (LIF).[7] Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEF's) and require the presence of basic Fibroblast Growth Factor (bFGF or FGF-2).[8] Without optimal culture conditions or genetic manipulation[9] embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network which ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[10] The cell surface proteins most commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[11]
After 20 years of research, there are no approved treatments or human trials using embryonic stem cells. Their tendency to produce tumors and malignant carcinomas, cause transplant rejection, and form the wrong kinds of cells are just a few of the hurdles that embryonic stem cell researchers still face.[12] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.
