For the first time in medical history, a team of researchers has grown and sustained blood stem cells in a bioreactor. The resulting cells could replace painful bone marrow transplants used to produce hematopoietic cells in patients suffering from leukemia and other blood cancers.
For the first time in medical history, researchers have grown and sustained blood stem cells (also called hematopoietic stem cells) in a bioreactor. The resulting cells could replace painful bone marrow transplants used to produce hematopoietic cells in patients suffering from leukemia and other blood cancers.
Blood cancers are caused by blood cell malfunctions that originate in the bone marrow, the spongy core of the bone that generates hematopoietic stem cells, which give rise to red, white, platelet, and all other blood cells in the body. Many of these cells are short-lived, and humans must produce about 500 billion daily to meet demand.
Blood cancers interfere with the body’s ability to replenish its blood cells. Clinicians usually treat these diseases with a combination of chemotherapy to kill the cancer cells and bone marrow transplants capable of producing new blood stem cells. Transplants are physically painful and costly, and require finding suitable donors with similar ancestry.
Yet even with treatment, 160 people die of blood cancers each day in the United States. The Leukemia and Lymphoma Society projects that in 2018, physicians will diagnose 60,000 people with leukemia and more than 24,000 will die from the disease.
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The developers of the new bioreactor, Ivan Martin of University of Basel’s department of biomedicine, and Timm Schroeder of ETH Zurich’s department of biosystems science and engineering, hope their system will lead to the generation of bone marrow cells on demand.
The ability to harvest, sustain, and grow hematopoietic stem cells on demand—especially from a patient’s own cells—would be a paradigm shift for blood cancer treatment. So far, the bioreactor has kept hematopoietic cells alive and regenerating for up to two weeks. The researchers believe the system has the potential to grow cells for longer periods.
The hematopoietic cells are picky customers. They can only regenerate within the bone marrow, a type of tissue found inside bone cavities. In the human body, a small number of healthy hematopoietic cells expand to a very large number of daughter cells. Once they move out of the bone marrow, they evolve into regular blood cells and stop regenerating themselves.
Recreating that synthetic biological and mechanical environment is far from simple. Researchers have been trying to mimic the natural bone marrow environment, or niche, in the lab for years, but it proved too complex to master, until now.
Martin and Schroeder created their artificial bone marrow by starting with a ceramic scaffold containing small cavities to mimic the bone matrix. They then populated the matrix with human mesenchymal stromal cells, which can differentiate into a variety of different cells like stem cells, and are normally part of the bone marrow niche.
“The mesenchymal cells are a special spongy network that structurally fill the bone marrow space and gives it the ability to generate that specialized environment we call niches,” Martin says. “The niche maintains hematopoietic stem cells and regulates when they should start dividing and generating their progeny.”
Inside the bioreactor, the team pumped the nutrient-rich medium through the scaffold. This enabled the mesenchymal cells attach to the ceramics, grow, and form a bone marrow-like environment.
Once the mesenchymal cells “settled in,” researchers added the hematopoietic stem cells to the medium and pumped them through the scaffold. By then, the synthesized environment’s molecular structure resembled parts of natural bone marrow niches enough to prompt the hematopoietic stem cells to regenerate.
The researchers kept the bioreactor going for two weeks and then stopped to analyze their findings, but they say that they have “data indicating that the timeframe of the stem cells can be further prolonged.”
The team did not replicate the bone marrow environment in its full biological complexity, Schroeder says. Instead, it built the structures needed to get the hematopoietic cells to replicate. There was no single eureka moment, he says, but rather a series of incremental improvements that took several years.
The technology holds promise for cancer treatment and research. Instead of bone marrow transplants or blood transfusions, physicians would be able to supply patients with synthetically grown hematopoietic stem cells, which would then produce all the other blood cells in their bodies, eliminating the need for donors, surgeries, and wait times.
The technology also provides scientists with a valuable test site for studying the physiology of hematopoietic cells in healthy conditions and during disease.
“At some point we may use malignant hematopoietic stem cells to generate the model of a leukemia,” Schroeder says.
This new platform may also let physicians test drugs before they administer them. For example, physicians can load malignant hematopoietic cells into the scaffold and apply drugs to gauge the cells’ response.
Theoretically, the platform can also be used to generate various cell types to fight specific forms of cancer, but it would take further experiments, researchers say.
Lina Zeldovich is an independent technical writer.
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