We are all programmed to have strong reactions to the vivid color of the life-giving fluid that runs through our veins. For some, it is a morbid fascination that causes them to watch horror movies, but for others it evokes terror and can often have a deeply profound effect when witnessed; phobia of blood is very common and can cause fainting in those who are particularly sensitive.
Researchers believe that, in fact, this is a deep-rooted reaction that may once have saved our lives in primitive times:
"If you’re a caveman and another caveman comes over and cuts your arm off, the sight of blood or injury may cause you to faint. So when you’re laying there on the ground, you’ll look like you’re dead to the other cavemen and he won’t cut your head off," explains Dr. Fred Jaeger, medical director of the Syncope Center at the Cleveland Clinic in Ohio.
Since the dawn of time, blood has been thought to carry our Life Force, and its use in rituals ancient and modern and across many cultures is well-documented. Its ability to save life is its most valuable asset in this modern age, and supplies of blood for medical use are a vital commodity for surgeries and many other life-saving purposes.
Blood transfusions from survivors are currently being used to help in the treatment of Ebola victims; the transfusions are not a cure as such, but provide a second line of defense for the body by bringing in anti-bodies that “modulate the severity” of the viral load in the victim’s blood, allowing a respite that allows them to produce antibodies on their own.
Whilst Ebola transfusions are a highly specialised and experimental use of blood supplies, even obtaining blood for standard transfusions is not easy. Currently, in highly developed countries, these supplies are obtained via non-remunerated, healthy volunteer repeat donors, but according to the World Health Organization (WHO), in most developing and transitional countries, family, replacement and paid blood donors are still a significant source of blood for transfusion. There are concerns that the risk of transmitting blood-borne pathogens from these blood product sources is much higher, and stocks of safe blood can only be assured by regular donations from unpaid, voluntary blood donors.
Obtaining reliable supplies can therefore pose quite a problem for the medical profession, so considerable research has been conducted into viable alternatives.
Is it actually possible for blood to be made to order?
Scientists now believe that their ability to reliably and safely make in the laboratory all of the different types of cells in human blood is one key step closer to reality.
Writing in the the journal Nature Communications, a group led by University of Wisconsin-Madison stem cell researcher Igor Slukvin reports the discovery of two genetic programs responsible for taking blank-slate stem cells and turning them into both red and the array of white cells that make up human blood.
The research is important because it identifies how nature itself makes blood products at the earliest stages of development. The discovery gives scientists the tools to make the cells themselves, investigate how blood cells develop and produce clinically relevant blood products.
“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” explains Slukvin, referencing the proteins that bind to DNA and control the flow of genetic information, which ultimately determines the developmental fate of undifferentiated stem cells.
During development, blood cells emerge in the aorta, a major blood vessel in the embryo. There, blood cells, including hematopoietic stem cells, are generated by budding from a unique population of what scientists call hemogenic endothelial cells. The new report identifies two distinct groups of transcription factors that can directly convert human stem cells into the hemogenic endothelial cells, which subsequently develop into various types of blood cells.
The factors identified by Slukvin’s group were capable of making the range of human blood cells, including white blood cells, red blood cells and megakaryocytes, commonly used blood products.
“By over-expressing just two transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo” where blood is made, says Slukvin of the Department of Pathology and Laboratory Medicine in the UW School of Medicine and Public Health and the Wisconsin National Primate Research Center.
The method developed by Slukvin’s group was shown to produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.
A critical aspect of the work is the use of modified messenger RNA to direct stem cells toward particular developmental fates. The new approach makes it possible to induce cells without introducing any genetic artifacts. By co-opting nature’s method of making cells and avoiding all potential genetic artifacts, cells for therapy can be made safer.
“You can do it without a virus, and genome integrity is not affected,” Slukvin notes.
Moreover, while the new work shows that blood can be made by manipulating genetic mechanisms, the approach is likely to be true as well for making other types of cells with therapeutic potential, including cells of the pancreas and heart.
An unfulfilled aspiration, says Slukvin, is to make hematopoietic stem cells, multipotent stem cells found in bone marrow. Hematopoietic stem cells are used to treat some cancers, including leukemia and multiple myeloma. Devising a method for producing them in the lab remains a significant challenge.
“We still don’t know how to do that,” Slukvin notes, “but our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”
Good news for the medical profession and – we had to say it – for vampires too!