Now pregnant mothers can cure blood diseases of their unborn babies
By IANS
Wednesday, 19 January 2011, 01:05 Hrs
London: Scientists have developed a stem cell cure for deadly blood related diseases in unborn babies.
Researchers extracted bone marrow cells from a pregnant mother and injected these into the developing foetus.
The donor cells were accepted by the foetus's growing immune system without the need for any drugs, the Journal of Clinical Investigation reports.
The experiment carried out on animals is the first time that scientists have been able to successfully transplant a mother's stem cells into her offspring before birth, according to the Daily Mail.
The technique could be used to treat a range of genetic diseases, including sickle cell anaemia or bubble boy disease, the immune system disorder that leaves babies vulnerable to normally harmless infections.
Tippi MacKenzie, who led the study at the University of California - San Francisco, said: "This research is really exciting because it offers us a straightforward, elegant solution that makes foetal stem cell transplantation a reachable goal."
"We now, for the first time, have a viable strategy for treating congenital stem cell disorders before birth."
Doctors say developing babies are ideal candidates for transplants because the risk of rejection is low and because they are less likely to need long-term drugs to suppress their immune systems.
However, most past attempts to transplant blood stem cells into a child in the womb have failed.
The new study found that a mother's immune response prevents foetuses from accepting donor blood stem cells. When the researchers transplanted stem cells from the mother, the foetus accepted them.
Stem cell breakthrough for birth defects
2011-01-18 21:38
Washington - US researchers have discovered why foetal stem cell transplants, once considered a promising field for treating congenital defects before birth, were failing: it was all the mother's fault.
But mom's cells could also be the solution, according to a study on mice released on Tuesday in the Journal of Clinical Investigation.
The mistake may have been that doctors were trying to match transplantable bone marrow stem cells to the foetus. The mother's immune system would recognise the new cells as dangerous and reject them.
But if stem cells that match the mother were implanted, scientists saw a near 100% success rate, said the study.
"This research is really exciting because it offers us a straightforward, elegant solution that makes foetal stem cell transplantation a reachable goal," said senior author Tippi MacKenzie at the University of California, San Francisco.
"We now, for the first time, have a viable strategy for treating congenital stem cell disorders before birth."
If the process works in humans, doctors could use it to treat a variety of inherited immune disorders which can be detected through prenatal testing, such as sickle cell disease, thalassemia, chronic granulomatous disease and others.
Conundrum
The advance could erase what researchers describe as a "decade-long scientific conundrum" that has caused many to lose interest in the field.
"The fact that foetal stem cell transplantation has not been very successful has been puzzling, especially given the widely accepted dogma that the immature foetal immune system can adapt to tolerate foreign substances," said co-author Qizhi Tang at the UCSF Transplantation Research Lab.
"The surprising finding in our study is that the mother's immune system is to blame."
Using a variety of mouse models for study, researchers looked at the content of the foetus's blood and found that 10% of it matched maternal blood cells, a higher proportion than anywhere else in the developing mouse's body.
Tolerance
Then they transplanted mice with blood stem cells that matched neither the foetus nor the mother to see what would happen.
A rush of T-cells, which protect the body from infection, surged from the mother into the foetus, forcing the rejection of the transplanted cells.
But when researchers transplanted blood stem cells that matched the mother, the process was usually successful because the mother's immune system did not recognise them as dangerous.
"As long as the transplanted stem cells are matched to the mother, it does not seem to matter if they are matched to the foetus," said co-author Amar Nijagal, a postdoctoral research fellow and surgery resident at UCSF.
"Transplanting stem cells harvested from the mother makes sense because the mother and her developing foetus are pre-wired to tolerate each other."
Researchers hope to look next at whether the process will work in humans.
- SAPA
Gene Therapy Helps Treat Beta Thalassemia
Drug Discovery & Development - January 11, 2011
Researchers at Nationwide Children's Hospital report a gene therapy strategy that improves the condition of a mouse model of an inherited blood disorder, Beta Thalassemia. The gene correction involves using unfertilized eggs from afflicted mice to produce a batch of embryonic stem cell lines. Some of these stem cell lines do not inherit the disease gene and can thus be used for transplantation-based treatments of the same mice. Findings could hold promise for a new treatment strategy for autosomal dominant diseases like certain forms of Beta Thalassemia, tuberous sclerosis or Huntington's disease.
Embryonic stem cells have the potential to produce unlimited quantities of any cell type and are therefore being explored as a new therapeutic option for many diseases. Unfertilized eggs can be cultured to form embryonic stem cells, so-called parthenogenetic embryonic stem cells.
"Parthenogenetic embryonic stem cells can differentiate into multiple tissue types as do stem cells from fertilized embryos," said K. John McLaughlin, PhD, principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children's Hospital. Previously, the group demonstrated that blood cells derived from parthenogenetic cells could provide healthy, long-term blood replacement in mice.
"Advantages of parthenogenetic stem cells are not only that fertilization is not needed, but also that the recipient's immune system may potentially not view them as foreign, minimizing rejection problems. Furthermore, since parthenogenetic embryonic stem cells are derived from reproductive cells which contain only a single set of the genetic information instead of the double set present in body cells, they may not contain certain abnormal genes present in the other copy," said Dr. McLaughlin also one of the study authors.
A single copy of an abnormal gene inherited from one parent can cause so-called autosomal dominant diseases such as tuberous sclerosis or Huntington's disease. The affected person has one defective and one normal copy of the gene, but the abnormal gene overrides the normal gene, causing disease. In normal sexual reproduction, each parent provides one gene copy to offspring via their reproductive cells. Therefore, the reproductive cells of a patient with an autosomal dominant disease could either pass along a defective copy or a normal copy.
"As the donor patient has one defective gene copy and one normal, and only one copy is used for normal reproduction, we can select egg-cell-derived embryonic stem cells with two normal copies," said Dr. McLaughlin. "These single-parent/patient-derived embryonic stem cells can theoretically be used for correction of a diverse number of diseases that occur when one copy of the gene is abnormal," said Dr. McLaughlin.
To test this theory, Dr. McLaughlin and colleagues from the University of Pennsylvania, University of North Carolina and University of Minnesota, examined whether parthenogenetic embryonic stem cells could be used for tissue repair in a mouse model of thalassemia intermedia. Thalassemia intermedia is an inherited blood disorder in which the body lacks sufficient normal hemoglobin, leading to excessive destruction of red blood cells and anemia. They used a mouse model in which one defective gene copy causes anemia.
Using approaches developed from a previous study done by this group, Nationwide Children's Research Fellow Sigrid Eckardt, PhD, derived embryonic stem cells from the unfertilized eggs of female mice with the disease, and identified those stem cell lines that contained only the "healthy" hemoglobin genes. These "genetically clean" embryonic stem cell lines were converted into cells that were transplanted into afflicted mice that were carriers of the disease causing gene. Blood samples drawn five weeks after transplantation revealed that the delivered cells were present in the recipients' blood. Their red blood cells were also corrected to a size similar to normal mice and red blood cell count, hematocrit and hemoglobin levels became normal.
"Overall, we observed long-term improvement of thalassemia in this model," said Dr. Eckardt. "Our findings suggest that using reproductive cells to generate embryonic stem cells that are 'disease-free' may be a solution for genetic diseases involving large, complex or poorly identified deletions in the genome or that are not treatable by current gene therapy approaches." Dr. McLaughlin says that this approach also contrasts with typical gene therapy approaches in that it requires no engineering of the genome, which is currently difficult to achieve in human embryonic and embryonic-like (IPS) stem cells.
Date: January 10, 2011
Source: Nationwide Children's Hospital