In what researchers at Newcastle University in the U.K. have dubbed a "eureka moment," a miniature human liver has been grown artificially in a laboratory through the use of stem cells, which may mean that in the future, full-sized organs could be artificially grown for transplants. Tissues such as this one could also be used to test the effects of new drugs, circumventing disasters such as the TGN-1412 trial. In that test, now known in the press as the "elephant man drug trial," the bodies of six volunteers flared up to dangerous levels after being administered an experimental drug, leaving at least one with terminal cancer. Having artificial tissue to test on could also mean fewer animal experiments, the researchers noted.Within five years, grown liver tissue could repair livers damaged by injury, disease, alcohol abuse, and over-the-counter painkiller overdose, and entire livers could be quickly replaced roughly 15 years from now, the researchers said. In 2004, 72 people in the U.K. died while waiting for a suitable transplant donor, and there are currently 336 people on the liver transplant list there.The miniature liver, approximately the size of a penny, was grown from stem cells. These blank cells are found in the blood from the umbilical cord and can be turned into specific types of tissue when removed from the umbilical cord minutes after a baby is born. Scientists then place the cells in a NASA-developed "bioreactor," which simulates weightlessness. Without the effects of gravity, the cells multiply more quickly, after which various hormones and chemicals are added to cause the stems cells to transform into liver tissue.
Stem cell research, especially embryonic stem cell research, has caused a lot of controversy since it usually requires the destruction of a human embryo, but this technique is considered more ethically acceptable as no such destruction is required. The Newcastle researchers postulated a worldwide donor register for liver dialysis and transplant could be formulated if the umbilical blood of millions of babies is preserved each year, using a computer registry to track blood compatibility. More than 11,000 British parents already freeze their children's umbilical blood, which is used to treat leukemia. "One hundred million children are born around the world every year -- that is 100 million different tissue types," said Colin McGuckin, professor of regenerative medicine at Newcastle University. "With that number of children being born every year, we should be able to find a tissue for me and you and every other person who doesn't have stem cells banked." "The stem cell is going to change the way we deliver treatment," he said. "However, it won't happen tomorrow." Mike Adams, a consumer health advocate and author of the free health guides at Truth Publishing, had an even stronger warning. "The growing of artificial organs in a laboratory may seem like an amazing medical breakthrough, but the issue is far more complex than most people realize. We should observe this with extreme caution and skepticism," he said. "While scientists are working feverishly to figure out how to grow a replacement organ in the lab, for example, no one is teaching patients how to take care of the liver they already have. "The emphasis in medicine is on expensive, heroic treatments such as transplants, yet conventional medicine utterly ignores what patients need most: prevention of disease and the support of the vital organs they were born with," Adams said.
Saturday, July 17, 2010
Friday, July 16, 2010
Examining the importance of banking 'Cord Blood Stem Cells'.
The decision to bank cord blood is a hot topic these days. Cord blood contains stem cells that are the building blocks of our blood and immune system. Drawn from the umbilical cord at the time of childbirth it is becoming more practiced as expectant parents are being exposed to information on the subject via the media, their doctors and their government. Cord blood stem cells from one umbilical cord at the time of birth can potentially treat any member of your immediate family.
It is now an accepted fact within the medical establishment that cord blood stem cells from the umbilical cord can treat (and sometimes cure) over 70 life-threatening diseases, including a wide range of cancers, genetic diseases, immune system deficiencies and blood disorders. Studies are currently under way regarding treatment for Type 1 Diabetes and Cerebral palsy. Researchers are also hopeful cord blood stem cells may be able to treat heart disease and stroke in the near future.
Banking cord blood is a simple procedure. Performed by the doctor or midwife just after the birth of the baby and before the placenta is delivered, a 4 to 8 inch section of umbilical cord is cleaned with an antiseptic solution and a blood bag needle is inserted into the umbilical vein until the collection is completed. This in no way interferes with the health and safety of the mother and child, and often takes under 5 minutes. The blood bag is sent to storage at a pre-arranged blood cord bank of your choice.
The importance of stem cells is powerful as they have the ability to not only treat diseases but actually repair and replace damaged cells in the body. Anthony and Tammy Witherspoon of McComb, MS know this all too well.
“My wife and I gave birth to a baby boy in 1994 named Anthony II. Approximately four months later, we were informed that our son had been diagnosed with sickle-cell disease. In 2000, our son suffered a stroke; unfortunate as that may be, the incident qualified him to participate in a research program offered at the Batson Children Cancer Clinic in Jackson, MS. In doing our research, we began to learn about the possibilities of curing sickle-cell disease with stem cells.
On September 20, 2004, we gave birth to another baby boy. We immediately collected the umbilical cord blood and shipped it for storage. The blood test results came back a couple of weeks later. Not only did our newborn not have sickle-cell, he was also a match for a donor.
In October 2005, we checked into the transplant unit at the University Medical Center in Jackson, MS. The transplant was performed, and we are grateful today to be able to say that our son has been cured of sickle-cell disease.
Cord blood can be used from a donor-matched non-family member; however stats show a 50% higher success rate when cord blood is used from a family member.
It is now an accepted fact within the medical establishment that cord blood stem cells from the umbilical cord can treat (and sometimes cure) over 70 life-threatening diseases, including a wide range of cancers, genetic diseases, immune system deficiencies and blood disorders. Studies are currently under way regarding treatment for Type 1 Diabetes and Cerebral palsy. Researchers are also hopeful cord blood stem cells may be able to treat heart disease and stroke in the near future.
Banking cord blood is a simple procedure. Performed by the doctor or midwife just after the birth of the baby and before the placenta is delivered, a 4 to 8 inch section of umbilical cord is cleaned with an antiseptic solution and a blood bag needle is inserted into the umbilical vein until the collection is completed. This in no way interferes with the health and safety of the mother and child, and often takes under 5 minutes. The blood bag is sent to storage at a pre-arranged blood cord bank of your choice.
The importance of stem cells is powerful as they have the ability to not only treat diseases but actually repair and replace damaged cells in the body. Anthony and Tammy Witherspoon of McComb, MS know this all too well.
“My wife and I gave birth to a baby boy in 1994 named Anthony II. Approximately four months later, we were informed that our son had been diagnosed with sickle-cell disease. In 2000, our son suffered a stroke; unfortunate as that may be, the incident qualified him to participate in a research program offered at the Batson Children Cancer Clinic in Jackson, MS. In doing our research, we began to learn about the possibilities of curing sickle-cell disease with stem cells.
On September 20, 2004, we gave birth to another baby boy. We immediately collected the umbilical cord blood and shipped it for storage. The blood test results came back a couple of weeks later. Not only did our newborn not have sickle-cell, he was also a match for a donor.
In October 2005, we checked into the transplant unit at the University Medical Center in Jackson, MS. The transplant was performed, and we are grateful today to be able to say that our son has been cured of sickle-cell disease.
Cord blood can be used from a donor-matched non-family member; however stats show a 50% higher success rate when cord blood is used from a family member.
Molecular similarity: a key technique in molecular informatics
Molecular Informatics utilises many ideas and concepts to find
relationships between molecules. The concept of similarity,
where molecules may be grouped according to their biological
effects or physicochemical properties has found extensive use
in drug discovery. Some areas of particular interest have been
in lead discovery and compound optimisation. For example,
in designing libraries of compounds for lead generation, one
approach is to design sets of compounds ‘similar’ to known
active compounds in the hope that alternative molecular
structures are found that maintain the properties required while
enhancing e.g. patentability, medicinal chemistry opportunities
or even in achieving optimised pharmacokinetic profiles. Thus
the practical importance of the concept of molecular similarity
has grown dramatically in recent years. The predominant users
are pharmaceutical companies, employing similarity methods
in a wide range of applications e.g. virtual screening, estimation
of absorption, distribution, metabolism, excretion and toxicity
(ADME/Tox) and prediction of physicochemical properties
(solubility, partitioning etc.). In this perspective, we discuss the
representation of molecular structure (descriptors), methods
of comparing structures and how these relate to measured
properties. This leads to the concept of molecular similarity,
its various definitions and uses and how these have evolved
in recent years. Here, we wish to evaluate and in some cases challenge accepted views and uses of molecular similarity.Molecular similarity, as a paradigm, contains many implicit and explicit assumptions in particular with respect to the prediction
of the binding and efficacy of molecules at biological receptors.
The fundamental observation is that molecular similarity has
a context which both defines and limits its use. The key issues
of solvation effects, heterogeneity of binding sites and the
fundamental problem of the form of similarity measure to use are addressed.
A DYNAMIC AREA:
Molecular similarity is a dynamic and evolving area of
research and has been regularly reviewed. Johnson and
Maggiora1 and Dean6 wrote comprehensive books in this area.
Recently, books by Leach and Gillet and Gasteiger have included
sections on molecular similarity. Recent general reviews
of molecular similarity are given by Willett et al.,Walters etal., Gillet et al and Bajorath,a good critique, particularly
of the misuse of similarity measures is given by Nikolova
and Jaworska. A justification for the large number of molecular
similarity methods is given by Sheridan and Kearsley.7
Bajorath discusses the role of similarity in the integration of
in silico and in vitro screening,while Johnson et al.attempts
to characterize similarity methods (at least those known at that
time). Some caveats of molecular similarity such as different
mechanisms of action and target-dependent similarity are discussed
by Kubinyi. Finally the reader is referred to Tversky,
who describes early approaches to similarity in psychological
testing which have been adopted by later researchers to describe
similarity in molecules. Of interest here is that similarity assessments
are influenced by ‘context, perspective, choice alternatives
and expertise’. The choice of features, transformations
and structural descriptions to describe entities (molecules in our
case) will govern the predictions made by similarity models as
much as do the model’s mechanisms for comparing and integrating
these representations.
The fundamental observation that we can derive from these
facts is that similarity has a context. Two vials of a yellow compound
may be very similar in colour (absorption spectrum)
but wildly different in biological activity. How far the context
of a particular similarity argument can be taken (the ‘neighbourhood
effect’) also depends on the discontinuities found in
receptor–ligand interactions; clearly, the similarities studied are
seldom linear and often have major discontinuities.In this perspective we have reviewed progress in molecular similarity
methods and applications and highlighted some of the
more challenging problems and assumptions.
Molecular similarity is extensively and successfully used in
the drug discovery context often to compare molecules in the
absence of other mechanistic information (a partial exception
is the docking applications described above). Most importantly,
similarity has a context. One has to be aware that similarity
defined on molecules alone in the absence of the medium in
which they act is an incomplete description so great care has to
be taken to use descriptors that are appropriate.
The discontinuous nature of biological effects such as ligand–
receptor binding means that linear regression techniques are
only appropriate for QSAR and related applications if a linear
relationship between feature space and activity exists. In general
it is often more appropriate to use nonparametric or non-linear
regression techniques. The example of electrostatic effects and
their discontinuous relationship with solvation energies is an
example.
Back-projectable descriptors (compared to descriptors without this property) possess better interpretability and will probably have more widespread use in the future. Binary bit strings in combination with similarity coefficients possess preferences with respect to bit density (and thus size of the molecule) and combinatorial preferences and one should be aware of these preferences when applying similarity methods. Applications of machine learning methods in computer-aided molecular design will certainly gain importance in the future particularly with the incorporation of heuristics that improve performance.As undarstanding of the chemistry and biology of drug action improves and a greater ability to model the underlying mechanisms appears, the need for ‘similarity’ approaches will diminish.
relationships between molecules. The concept of similarity,
where molecules may be grouped according to their biological
effects or physicochemical properties has found extensive use
in drug discovery. Some areas of particular interest have been
in lead discovery and compound optimisation. For example,
in designing libraries of compounds for lead generation, one
approach is to design sets of compounds ‘similar’ to known
active compounds in the hope that alternative molecular
structures are found that maintain the properties required while
enhancing e.g. patentability, medicinal chemistry opportunities
or even in achieving optimised pharmacokinetic profiles. Thus
the practical importance of the concept of molecular similarity
has grown dramatically in recent years. The predominant users
are pharmaceutical companies, employing similarity methods
in a wide range of applications e.g. virtual screening, estimation
of absorption, distribution, metabolism, excretion and toxicity
(ADME/Tox) and prediction of physicochemical properties
(solubility, partitioning etc.). In this perspective, we discuss the
representation of molecular structure (descriptors), methods
of comparing structures and how these relate to measured
properties. This leads to the concept of molecular similarity,
its various definitions and uses and how these have evolved
in recent years. Here, we wish to evaluate and in some cases challenge accepted views and uses of molecular similarity.Molecular similarity, as a paradigm, contains many implicit and explicit assumptions in particular with respect to the prediction
of the binding and efficacy of molecules at biological receptors.
The fundamental observation is that molecular similarity has
a context which both defines and limits its use. The key issues
of solvation effects, heterogeneity of binding sites and the
fundamental problem of the form of similarity measure to use are addressed.
A DYNAMIC AREA:
Molecular similarity is a dynamic and evolving area of
research and has been regularly reviewed. Johnson and
Maggiora1 and Dean6 wrote comprehensive books in this area.
Recently, books by Leach and Gillet and Gasteiger have included
sections on molecular similarity. Recent general reviews
of molecular similarity are given by Willett et al.,Walters etal., Gillet et al and Bajorath,a good critique, particularly
of the misuse of similarity measures is given by Nikolova
and Jaworska. A justification for the large number of molecular
similarity methods is given by Sheridan and Kearsley.7
Bajorath discusses the role of similarity in the integration of
in silico and in vitro screening,while Johnson et al.attempts
to characterize similarity methods (at least those known at that
time). Some caveats of molecular similarity such as different
mechanisms of action and target-dependent similarity are discussed
by Kubinyi. Finally the reader is referred to Tversky,
who describes early approaches to similarity in psychological
testing which have been adopted by later researchers to describe
similarity in molecules. Of interest here is that similarity assessments
are influenced by ‘context, perspective, choice alternatives
and expertise’. The choice of features, transformations
and structural descriptions to describe entities (molecules in our
case) will govern the predictions made by similarity models as
much as do the model’s mechanisms for comparing and integrating
these representations.
The fundamental observation that we can derive from these
facts is that similarity has a context. Two vials of a yellow compound
may be very similar in colour (absorption spectrum)
but wildly different in biological activity. How far the context
of a particular similarity argument can be taken (the ‘neighbourhood
effect’) also depends on the discontinuities found in
receptor–ligand interactions; clearly, the similarities studied are
seldom linear and often have major discontinuities.In this perspective we have reviewed progress in molecular similarity
methods and applications and highlighted some of the
more challenging problems and assumptions.
Molecular similarity is extensively and successfully used in
the drug discovery context often to compare molecules in the
absence of other mechanistic information (a partial exception
is the docking applications described above). Most importantly,
similarity has a context. One has to be aware that similarity
defined on molecules alone in the absence of the medium in
which they act is an incomplete description so great care has to
be taken to use descriptors that are appropriate.
The discontinuous nature of biological effects such as ligand–
receptor binding means that linear regression techniques are
only appropriate for QSAR and related applications if a linear
relationship between feature space and activity exists. In general
it is often more appropriate to use nonparametric or non-linear
regression techniques. The example of electrostatic effects and
their discontinuous relationship with solvation energies is an
example.
Back-projectable descriptors (compared to descriptors without this property) possess better interpretability and will probably have more widespread use in the future. Binary bit strings in combination with similarity coefficients possess preferences with respect to bit density (and thus size of the molecule) and combinatorial preferences and one should be aware of these preferences when applying similarity methods. Applications of machine learning methods in computer-aided molecular design will certainly gain importance in the future particularly with the incorporation of heuristics that improve performance.As undarstanding of the chemistry and biology of drug action improves and a greater ability to model the underlying mechanisms appears, the need for ‘similarity’ approaches will diminish.
Sunday, July 11, 2010
No quick drug fix for high diabetes risk .
Two key treatments do not halt diabetes in people with early signs of the disease, a large study has found.Researchers said the results showed the only way to ensure future health in people at high risk of diabetes is exercise and a healthy diet. Trials in more than 9,000 people also found no reduction in future heart problems in people prescribed two drug treatments compared with dummy pills. Diabetes UK said 7m people in the UK are at risk of developing diabetes. Everyone taking part in the study, published in the New England Journal of Medicine, had been diagnosed with what doctors call "impaired glucose tolerance". It effectively means that people have high blood sugar and their bodies are starting to not respond to insulin as well as they should.Sometimes called pre-diabetes, it is thought that the condition is a stage in the development of full-blown type 2 diabetes, and can be associated with obesity.It is thought that in the UK, around 17% of 35-65 year olds have impaired glucose tolerance.
Medical intervention:
In the trial, researchers in the US and UK looked at whether using a drug that lowers blood pressure or a drug which lowers blood sugar could be used to stop diabetes developing in these high-risk patients. But the results, from patients in 40 countries, found no great difference in how many people went on to get diabetes when prescribed either drug compared with a dummy pill. Neither did the drugs prevent future heart attacks and strokes, which are dangerous complications of the condition. In the blood-sugar lowering drug part of the study around a third of people went on to develop diabetes within five years whether they were taking the real medicine or dummy medicine.Professor Rury Holman, director of the Diabetes Trials Unit at the University of Oxford, said the treatments were proven to be effective once someone had diabetes but there was an "urgent need" for drugs to prevent the disease and its complications developing in the first place in those at high risk. He said: "The most successful treatment for someone at high risk of diabetes is diet and exercise."
'Dramatic difference':
Co-author Professor John McMurray from the University of Glasgow agreed that the results reinforced the importance of lifestyle changes in preventing diabetes. "Losing as little as 5% of body weight has been shown to make a dramatic difference in other studies." Dr Victoria King, research manager at Diabetes UK, said: "Unfortunately there is unlikely to be a quick and easy route to prevent type 2 diabetes and a healthy balanced lifestyle with a good diet and physical activity levels are the best preventative methods." But she added some drugs may be of benefit in these patients and the latest study would help doctors prescribe the most appropriate option.
Medical intervention:
In the trial, researchers in the US and UK looked at whether using a drug that lowers blood pressure or a drug which lowers blood sugar could be used to stop diabetes developing in these high-risk patients. But the results, from patients in 40 countries, found no great difference in how many people went on to get diabetes when prescribed either drug compared with a dummy pill. Neither did the drugs prevent future heart attacks and strokes, which are dangerous complications of the condition. In the blood-sugar lowering drug part of the study around a third of people went on to develop diabetes within five years whether they were taking the real medicine or dummy medicine.Professor Rury Holman, director of the Diabetes Trials Unit at the University of Oxford, said the treatments were proven to be effective once someone had diabetes but there was an "urgent need" for drugs to prevent the disease and its complications developing in the first place in those at high risk. He said: "The most successful treatment for someone at high risk of diabetes is diet and exercise."
'Dramatic difference':
Co-author Professor John McMurray from the University of Glasgow agreed that the results reinforced the importance of lifestyle changes in preventing diabetes. "Losing as little as 5% of body weight has been shown to make a dramatic difference in other studies." Dr Victoria King, research manager at Diabetes UK, said: "Unfortunately there is unlikely to be a quick and easy route to prevent type 2 diabetes and a healthy balanced lifestyle with a good diet and physical activity levels are the best preventative methods." But she added some drugs may be of benefit in these patients and the latest study would help doctors prescribe the most appropriate option.
Discovery Of Stem Cell Illuminates Human Brain Evolution, Points To Potential Stem Cell Therapies
A new stem cell has been discovered in the developing human brain. The cell produces nerve cells that help form the neocortex – the site of higher cognitive function—and likely accounts for the dramatic expansion of the region in the lineages that lead to man.In rodents and humans, the developing cortex contains a layer of neural stem cells called radial glial cells that resides near the fluid-filled ventricles and produces cells that are precursors to neurons. These precursor neurons can further proliferate in a region known as the subventricular zone (SVZ), to increase their numbers, and then differentiate into newborn neurons. The neurons then migrate along radial glial fibers up to the neocortex, where they help form the tissue that is the site of sensory perception, motor commands, spatial reasoning, conscious thought and language.In human and nonhuman primates, however, the SVZ has a massively expanded outer region, known as the outer subventricular zone (OSVZ). About 20 years ago, scientists presumed that the OSVZ also contained stem cells, but until now they have lacked evidence.In the current study, lead authors David V. Hansen, PhD, a postdoctoral fellow, and Jan H. Lui, a graduate student in the Arnold Kriegstein lab at the University of California San Francisco, examined the OSVZ, using new labeling and tracking techniques to follow individual cells and their progeny over time in cultured tissue slices from fetal cortex tissue that had been donated for research.They characterized two kinds of cells within the region—both the novel neural stem cell and its daughter cell, known as the transit amplifying cell. The stem cell closely resembles the radial glial cell in structure and behavior and, like the radial glia, has radial fibers which newborn neurons migrate along up to the neocortex. The region is a busy hub of cell proliferation. The stem cell undergoes asymmetrical cell division, giving rise to two distinct daughter cells—one a copy of the original stem cell, the other a transit amplifying cell. The transit amplifying cell undergoes multiple rounds of symmetrical divisions before all of its daughter cells begin the process of differentiating into neurons. We are very interested in understanding how these modes of division are regulated,” said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. “We suspect that faults in cell-cycle regulation account for a variety of developmental brain diseases.”
More broadly, he said the team wants to understand how the new stem cells compare to radial glial cells and how the two sets of neurons they produce integrate in the neocortex. “Neurons are probably being generated in both the SVZ and OSVZ at once,” he says. “They likely end up in the same layer of the neocortex as they migrate into position and start forming circuits. “This suggests to us that there may be a mosaic of cell types in the human neocortex, in which there are cells that originate in the traditional zone and cells produced in the newer zone that intermix in the cortex. The complexity of primate neocortex may be significantly increased by the interaction of the evolutionarily-speaking ‘younger’ neurons with those originating in the more primitive zone.”
The massive number of cells within the OSVZ of humans “tells us we have to be careful when modeling human brain diseases in mice,” says Kriegstein. “Especially in the neocortex—the most highly developed part of the brain in primates and humans – there are going to be important differences between rodents and humans.”
More broadly, he said the team wants to understand how the new stem cells compare to radial glial cells and how the two sets of neurons they produce integrate in the neocortex. “Neurons are probably being generated in both the SVZ and OSVZ at once,” he says. “They likely end up in the same layer of the neocortex as they migrate into position and start forming circuits. “This suggests to us that there may be a mosaic of cell types in the human neocortex, in which there are cells that originate in the traditional zone and cells produced in the newer zone that intermix in the cortex. The complexity of primate neocortex may be significantly increased by the interaction of the evolutionarily-speaking ‘younger’ neurons with those originating in the more primitive zone.”
The massive number of cells within the OSVZ of humans “tells us we have to be careful when modeling human brain diseases in mice,” says Kriegstein. “Especially in the neocortex—the most highly developed part of the brain in primates and humans – there are going to be important differences between rodents and humans.”
Saturday, July 10, 2010
Hematopoietic stem cell transplantation (HSCT)
The last fifty years have seen major advances in the field of medical research, many of which were translated into clinical applications. In general these applications have brought immense benefits to patients. As many of these new clinical applications are quite radical and often controversial, they inevitably challenge conventional ethical principles. Solid organ transplantation is one such advance which has generated and continues to generate issues involving ethics, law and morality. Organ transplantation has become an effective form of treatment particularly for end stage heart, liver and kidney failure. Except for kidney failure, organ transplantation is the only form of possible treatment for the other organ failure states, like the heart or the liver.The success rate in solid organ transplantation generally has improved since the first heart transplant 40 years ago, and this is as a result of our ability to control the transplant patient’s immune response. This has reduced the incidence of acute graft loss and the side effects of immunosuppressive regimens and given greater confidence among transplant surgeons who now believe that organ transplantation should no more be reserved for life-threatening organ failure but should also be available for structural non-life threatening defects. Thus we have increasingly seen hand transplants, laryngeal transplants along with knees, nerves, and flexor tendon apparatus of the hand. But these are reconstructive transplants and need to be differentiated from the more complex organ transplantation.
From the beginning, issues involving ethics have dominated the field of organ transplantation. This is not surprising as transplantation involves the use of human donors who may be alive or dead. Further the persistent shortage of organs in relation to the number of patients needing transplantation has led to problems of allocation. The success of transplantation, as measured by survival of the transplanted organs, has improved considerably in recent years. But the continued shortage of organs for transplantation has led to an unsavory aspect of transplantation, that of trafficking in organs, with all the attendant social, moral and ethical issues. Ethical issues in organ transplantation can be broadly categorized into issues relating to organ donation and those that relate to organ allocation.Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is, bone marrow transplantation) or blood. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer.Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease.Hematopoeitic stem cell transplantation remains a risky procedure with many possible complications; it has always been reserved for patients with life-threatening diseases.Most recipients of HSCTs are leukemia patients who would benefit from treatment with high doses of chemotherapy or total body irradiation. Other conditions treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's Sarcoma, Desmoplastic small round cell tumor, Hodgkin's disease, and multiple myeloma. More recently non-myeloablative, or so-called "mini transplant," procedures have been developed that require smaller doses of preparative chemo and radiation.
Hematopoietic Stem Cell Transplant- Graft Types/Donors/HSC Sources & Storage:
Graft types: Autolgous Graft Allogeneic Graft
Autologous HSCT involves isolation of HSC from the patient, storage of the harvested cells hematopoeitic stem cells in a freezer, high-dose chemotherapy to eradicate the patient's malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. Autologous transplants have the advantage of a lower risk of graft rejection and infection, since the recovery of immune function is rapid. The incidence of a patient experiencig graft-versus-host diseaseis close to none , the donor and recipient are the same individual.
Allogeneic HSCT involves two people, one is the (normal) donor and one is the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the (HLA) gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely matched HLA sibling) or unrelated(donor who is not related and found to have very close degree of HLA matching ) . Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells.
Sources of HSC Peripheral blood stem cells are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, which mobilizes stem cells from the donor's bone marrow into the peripheral circulation
Umbilical cord blood is obtained when parents elect to harvest and store the blood from a newborn's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood.
Storage of HSC Unlike other organs, bone marrow cells can be frozen for prolonged time periods (cryopreserved) without damaging too many cells. This is necessary for
autologous HSC because the cells must be harvested months in advance of the transplant treatment. In the case of allogeneic transplants fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC a preservative, DMSO, must be added and the cells must be cooled very slowly in a control rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer which typically utilizes liquid nitrogen because it is non-toxic and it is very cold (boiling point -196°C.)
From the beginning, issues involving ethics have dominated the field of organ transplantation. This is not surprising as transplantation involves the use of human donors who may be alive or dead. Further the persistent shortage of organs in relation to the number of patients needing transplantation has led to problems of allocation. The success of transplantation, as measured by survival of the transplanted organs, has improved considerably in recent years. But the continued shortage of organs for transplantation has led to an unsavory aspect of transplantation, that of trafficking in organs, with all the attendant social, moral and ethical issues. Ethical issues in organ transplantation can be broadly categorized into issues relating to organ donation and those that relate to organ allocation.Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is, bone marrow transplantation) or blood. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer.Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease.Hematopoeitic stem cell transplantation remains a risky procedure with many possible complications; it has always been reserved for patients with life-threatening diseases.Most recipients of HSCTs are leukemia patients who would benefit from treatment with high doses of chemotherapy or total body irradiation. Other conditions treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's Sarcoma, Desmoplastic small round cell tumor, Hodgkin's disease, and multiple myeloma. More recently non-myeloablative, or so-called "mini transplant," procedures have been developed that require smaller doses of preparative chemo and radiation.
Hematopoietic Stem Cell Transplant- Graft Types/Donors/HSC Sources & Storage:
Graft types: Autolgous Graft Allogeneic Graft
Autologous HSCT involves isolation of HSC from the patient, storage of the harvested cells hematopoeitic stem cells in a freezer, high-dose chemotherapy to eradicate the patient's malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. Autologous transplants have the advantage of a lower risk of graft rejection and infection, since the recovery of immune function is rapid. The incidence of a patient experiencig graft-versus-host diseaseis close to none , the donor and recipient are the same individual.
Allogeneic HSCT involves two people, one is the (normal) donor and one is the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the (HLA) gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely matched HLA sibling) or unrelated(donor who is not related and found to have very close degree of HLA matching ) . Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells.
Sources of HSC Peripheral blood stem cells are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, which mobilizes stem cells from the donor's bone marrow into the peripheral circulation
Umbilical cord blood is obtained when parents elect to harvest and store the blood from a newborn's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood.
Storage of HSC Unlike other organs, bone marrow cells can be frozen for prolonged time periods (cryopreserved) without damaging too many cells. This is necessary for
autologous HSC because the cells must be harvested months in advance of the transplant treatment. In the case of allogeneic transplants fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC a preservative, DMSO, must be added and the cells must be cooled very slowly in a control rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer which typically utilizes liquid nitrogen because it is non-toxic and it is very cold (boiling point -196°C.)
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