Monday November 8 2010
Blood donors are still vital
“Future patients needing blood for surgery can have a transfusion made from a patch of their own skin,” reported the Daily Mirror.
This news story is based on research showing that different types of blood cell can be produced in the laboratory from human skin cells. This was achieved without the skin cells having to be converted into stem cells first.
This is important research and may pave the way towards patients eventually being able to generate their own blood for transfusion from their skin cells. However, much more research is needed to make sure that these cells behave like normal blood cells, do not carry any side effects, and to identify how these cells can be used in clinical treatments and in what types of patients. Blood donors are still vital and will remain so for the foreseeable future.
Where did the story come from?
This study was carried out by researchers from McMaster University in Canada. Funding was provided by the Canadian Institute of Health Research, the Canadian Cancer Society Research Institute, the StemCell Network and the Ontario Ministry of Research Innovation. It was published in the peer-reviewed scientific journal Nature.
The Daily Mirror, Daily Express, Daily Mail, and Daily Telegraph reported this research. The reports are generally accurate, focusing on the potential clinical applications of this new technique. It is important to make clear that the new technique is not yet at a stage where it can be used to treat patients. Some newspapers suggested that it may be available by 2012, but this will depend on the results of further research.
What kind of research was this?
This laboratory research looked at whether cells from adult human skin could be ‘transformed’ into blood cells. The researchers say previous lab studies have successfully transformed mouse skin cells into other types of cells, such as nerve cells or heart muscle cells, and they wanted to see if the same techniques could be used on human skin cells.
Generally it is thought that to change an adult cell into a different cell type in the laboratory, it has to first be ‘reprogrammed’ to become a stem cell (a type of cell that has the potential to become any cell type). The researchers found that during this conversion process in past experiments on human skin cells, some cells switch on or ‘express’ the OCT4 gene. The OCT4 gene encodes a protein that switches on other genes involved in making different cell types. The cells that express OCT4 also express a gene called CD45, which is typical of blood cells. The cells also begin to form colonies of cells that resemble blood cells in their shape. However, the cells do not express other genes that are typical of stem cells.
In this study, the researchers wanted to see if switching on the OCT4 gene in human skin cells might make them develop into blood cells, without having to revert to being stem cells first. They thought that if it worked, it might be a better way of making blood cells. This is because red blood cells made by stem cells make the embryonic form of haemoglobin (the pigment that carries oxygen in the blood) rather than the adult form.
Also, during the process of reprogramming adult cells to become stem cells, some cells are formed that can form tumours called teratomas. Therefore, a process that does not require cells to be transformed into stem cells might reduce the risk of these tumours.
What did the research involve?
The researchers used cells from samples of adult human skin and newborn foreskin for their experiments. A virus was created to carry an active form of the OCT4 gene into these cells. The same technique also carried two other genes called NANOG or SOX2 into separate batches of skin cells. These genes are also involved in making cells into different cell types. The researchers used these cells and untreated cells as controls to find out whether only OCT4 made the cells turn into blood cells.
These cells were then treated with compounds that encourage early blood cell development to see what effect this had. The researchers also explored whether the cells expressing OCT4 switched on a panel of genes that are essential for generating and maintaining stem cells.
Which genes were switched on and off in the OCT4-expressing cells was also examined, and whether this pattern resembled that of blood cells. The researchers also treated the cells with compounds that encourage the development of different blood cell types.
The researchers then tested the effect of these cells in mice. First, they injected mice that lack functioning immune systems with the OCT4 and CD45 expressing cells to see if the cells could survive and live in the mice’s bloodstreams.
Immunodeficient mice were also used in another part of the experiment, when they were injected with either the skin cells expressing OCT4 or untreated skin cells (six mice), or cells that had been reprogrammed to be stem cells (eight mice). The mice were monitored to see if they developed teratomas.
What were the basic results?
The researchers found that adult human skin and newborn foreskin cells expressing OCT4 formed colonies of cells. Skin cells expressing SOX2 or NANOG (untreated cells), did not do this.
The colonies of skin cells expressing OCT4 also switched on the blood cell gene CD45. In these cells, the genes that are usually expressed in skin cells also became less active. The cells expressing OCT4 did not switch on other genes essential for generating and maintaining stem cells.
When the cells expressing OCT4 were treated with compounds that encourage early blood cell development, they were better able to form colonies and switch on the CD45 gene. These compounds had no effect on skin cells not expressing OCT4.
The cells expressing OCT4 showed a pattern of switched on and switched off genes that was similar to that seen in certain types of blood cell, including the progenitor cells in umbilical cord blood, which can develop into different blood cell types. Recognising this, the researchers wanted to see if the OCT4-expressing cells could develop into different types of blood cells. They found that these cells could develop into cells with the characteristics of different types of blood cells if they were treated with different compounds to encourage this development. The blood cell types included macrophages, the white blood cells that can engulf and digest bacteria and other threatening microorganisms.
The researchers could also generate cells resembling other types of white blood cell, such as neutrophils, eosinophils and basophils, as well as red blood cells and the cells that produce platelets (megakaryocytes). The red blood cells produced adult haemoglobin rather than embryonic haemoglobin.
In the mouse experiments, OCT4 and CD45 expressing cells that were injected into immunodeficient mice survived, and 20% managed to ‘engraft’ themselves into the mice’s bone marrow, where blood producing cells are normally found.
Injecting mice with the OCT4 expressing cells or untreated skin cells did not cause them to develop teratomas.
How did the researchers interpret the results?
The researchers conclude that their findings show that human skin cells can be reprogrammed to develop into multiple different cell types. They say this suggests an alternative method of producing cell replacements from a person’s own cells, which avoids the problems associated with using stem cells.
This study suggests that it is possible to get human skin cells to convert into cells with characteristics of different types of blood cells, without having to convert them into stem cells first. Potentially this means that one day some patients might receive tailored blood transfusions that have been made using samples of their own skin.
However, much more research is needed to ensure these blood-like cells behave like natural blood cells and do not have any side effects. Researchers would also need to determine whether enough blood can be produced in this way for transfusion, and how long this would take. This technique is unlikely to remove the need for donated blood, as generating blood in this way would be likely to take time.
It is not clear whether this sort of technique could be adapted to be a potential alternative to peripheral blood stem cell transplant (PBSCT). PBSCT is mainly used to treat blood cancers and involves giving drugs to the patient to make them produce stem cells. These cells are then harvested from the blood and later re-transfused into the patient (usually following chemo or radiotherapy) so that they develop into new blood cells.
Overall, this is an important piece of research, but it will be some time before we know whether blood produced in this way could be used in clinical practice, and for which medical indications it would be suitable.