Bone marrow transplants are one of the more unpleasant medical procedures, with much of the discomfort due to the need to kill off the old marrow cells before introducing new ones. At the University of California San Diego (UCSD) Jacobs School of Engineering, a team of bioengineers led by Shyni Varghese is working on a type of artificial bone that may one day allow doctors to conduct bone marrow transplants with fewer side effects.

We tend to think of the skeleton as just the scaffolding that keeps us from sagging to the ground as an sloppy bag of organs, but it's much more than that. The long bones are hollow and contain bone marrow that produces 500 billion red blood cells each day through a process called hematopoiesis and lymphocytes that are so important to the immune system.

However, if something goes wrong with the marrow, such as through disease, the result is severe anemia and an impaired immune system. Sometimes this impairment is natural, either through cancer, some form of infection, a congenital condition, or an autoimmune problem. Or it may be artificially induced as a side effect of radiation or chemotherapy.

Whatever the cause, the most effective treatment is a bone marrow transplant or, more precisely, a hematopoietic stem cell transplant. The usual of way of effecting this is to either find a suitable donor who matches the patient's tissue type, or to collect healthy marrow from the patient, store it, and then reimplant it later.

The problem is, such a transplant requires killing off all the marrow cells in the patient's body through radiation or chemicals so the new cells won't be competing with the old ones. Unfortunately, this is a major procedure that puts a great strain on the body and causes side effects, including fatigue and fertility loss.

To avoid this, the UC San Diego team is working on a method to introduce new marrow cells into patients using artificial bones without having to destroy the host cells. That may sound counterproductive, but destroying the old cells is only imperative if they are themselves malignant, like in cases of leukemia. If the old cells are simply not working properly, such as in aplastic anemia, or have been impaired by radiation or chemotherapy to counter non-marrow cancers, then the question becomes how to get the new cells in without having to eliminate the old to make room for them.

The team's approach was to create a bioengineered biomimetic "accessory bone" that could be implanted into the body and house the donor cells without having to inject them into the long bones. They did this by manufacturing what looks like the circular bone out of a gammon steak. It is, in fact, a ring of porous hydrogel containing calcium phosphate minerals. When stem cells are introduced into this matrix, they develop into bone cells. Meanwhile, stem cells in the non-mineralized matrix in the center hold donor stem cells that turn into blood-producing cells.

To see how well this worked, the engineers introduced the implants under the skin of mice – some of which had functional bone marrow and others who had their marrow killed by radiation. Within four weeks, the implant developed bone-like structures complete with blood vessels and marrow that produced red blood cells. In addition, the implants and the bloodstream contained a mix of host and donor blood cells after six months.

The experiment not only showed that host and donor cells can exist side by side for long periods thanks to the implants, but also that the transplanted cells circulated through the bloodstream of the mice with the destroyed marrow as the implants functioned like natural bones.

"We're working on making this a platform to generate more bone marrow stem cells, says Varghese. "That would have useful applications for cell transplantations in the clinic.'

The research was published in PNAS.

Source: UC San Diego

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