Personalizing production of blood would reduce likelihood of rejection
Canadian scientists have transformed pinches of human skin into petri dishes of human blood -a major medical breakthrough that could yield new sources of blood for transfusions after cancer treatments or surgery.
The discovery, by researchers at McMaster University in Hamilton, Ont., could one day potentially allow anyone needing blood after multiple rounds of surgery or chemotherapy, or for blood disorders such as anemia, to have a backup supply of blood created from a tiny patch of their own skin -eliminating the risk of their body's immune system rejecting blood from a donor. Researchers predict the lab-grown blood could be ready for testing in humans within two years.
The achievement, published yesterday in the journal Nature, raises the possibility of personalizing blood production for patients for the first time.
"This is a very important discovery. I think it represents a seminal contribution" to the rapidly evolving field of stem-cell research, said Michael Rudnicki, scientific director of the Canadian Stem Cell Network and director of the Regenerative Medicine Program at the Ottawa Hospital Research Institute.
"That one can play with the fate of a cell and force it sideways into something that it doesn't at all resemble, and then being able to use it, is tremendously exciting."
The procedure is also relatively simple. It involves taking a small piece of skin, extracting fibroblasts - abundant cells in the skin that make up the connective tissue and give skin its flexibility -and bathing them in growth factors in a petri dish. Next, by adding a single protein that binds to DNA and acts as an on/off switch, the researchers turned on or off 2,000 genes and reprogrammed the skin cells to differentiate or morph into millions of blood progenitors -the cells the produce blood.
They generated multiple different blood-cell types - oxygen-ferrying red blood cells, infection-fighting white blood cells, cells that make platelets needed for healing, and macrophages, the garbage trucks of the blood system that swallow and break down foreign material.
The work was repeated several times over two years using skin from adults, as well as neonatal foreskin, demonstrating, according to background material, that it could work "for any age of person."
And while other researchers have reprogrammed fibroblasts into neurons, cardiac cells and even macrophage-like cells in mice, the McMaster team converted skin directly to blood using human skin.
The first to benefit could be patients with leukemia, whose blood undergoes genetic changes that turn it cancerous and who often need-bone marrow transplants, or those with lymphomas, such as Hodgkin's disease.
Bone marrow contains stem cells that produce blood cells. If the bone marrow is coming from a donor, "first of all, you have to find a match, which can often be a problem, especially for smaller ethnic groups," says Christine Williams, director of research at the Canadian Cancer Society Research Institute. There's also a risk of rejection, where the body sees the matched cells as foreign.
Using a patient's own bone marrow gets around the rejection risk. "But if you take the patient's own blood stem cells and put them back in after radiation, you're often re-transplanting cells that have the same mutation as the tumour," Williams says.
The skin cells of leukemia patients "don't have any genetic abnormalities," says Mick Bhatia, leader of the McMaster team. "So, if we could take the skin cells and generate blood, we could use that to transplant leukemic patients themselves."
The finding also has the potential of "making bone marrow transplant HLA (tissue) matching and paucity of donors a thing of the past," said Alain Beaudet, president of the Canadian Institutes of Health Research, which helped fund the study.
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