Engineered bone marrow could make transplants safer

May 8, 2017
Engineered bone with functional marrow. Credit: Varghese lab, UC San Diego

Engineers at the University of California San Diego have developed biomimetic bone tissues that could one day provide new bone marrow for patients needing transplants.

Bone marrow transplants are used to treat patients with . Before a transplant, a patient is first given doses of radiation, sometimes in combination with drugs, to kill off any existing stem cells in the patient's marrow. This pre-treatment is meant to improve success of the transplant by clearing up space in the marrow, allowing donor cells to survive and grow without competition from the patient's own cells. But this treatment often comes with harmful side effects, such as nausea, fatigue, loss of fertility and others.

To address these issues, a team led by bioengineering professor Shyni Varghese at the UC San Diego Jacobs School of Engineering has developed a bone-like implant that gives donor cells their own space to live and grow without competition, eliminating the need to wipe out the host's pre-existing cells.

"We've made an accessory bone that can separately accommodate donor cells. This way, we can keep the host cells and bypass irradiation," Varghese said.

Researchers developed bone tissues with functional bone marrow that can be filled with donor cells and implanted under the skin of mice. The donor cells survived for at least six months and supplied the mice with new blood cells. Varghese and her team published their work on May 8 in PNAS.

"In the future, our work could contribute to improved therapies for bone marrow disease," said Yu-Ru (Vernon) Shih, a research scientist in Varghese's lab and the study's first author.

Left: Cartoon illustration of long bone structure. Center: Image of engineered bone with marrow. Right: High magnification images of bone tissue (top) and marrow cells (bottom). Credit: Varghese lab, UC San Diego

Varghese cautions that these implants would be limited to patients with non-malignant bone marrow diseases, where there aren't any cancerous cells that need to be eliminated. Examples include aplastic anemia, in which the body can't make enough platelets and blood cells, as well as low blood counts and immune attack of the bone marrow caused by defective or abnormal bone marrow stem cells.

The implants mimic the structure of long bones in the body, consisting of an outer bone compartment and an inner marrow compartment. The implants are made of a porous hydrogel matrix. The outer matrix contains calcium phosphate minerals. Stem cells grown in this mineralized matrix differentiate into bone-building cells. The inner matrix houses donor stem cells that produce blood cells.

When implanted beneath the skin of mice, the structures matured into bone tissues that have a working blood vessel network and a bone marrow inside that supplies new blood cells. After four weeks, researchers found that the implanted marrow contained a mix of host and donor . They also found this mix circulating in the bloodstream of these mice even after 24 weeks.

According to researchers, these findings are significant because they indicate that: the implanted marrow is functional; cells can grow and survive for long time periods in the presence of host cells; and that host and can travel between the implanted marrow and the host's circulating blood—via the vessel network formed in the implanted bone tissue.

In another set of experiments, researchers took stem cells from the implanted marrow and transplanted them into a second group of mice that had their marrow stem cells destroyed by radiation and drugs. They found that the transplanted cells had diffused into the bloodstream of these mice. "We did these experiments to show that the from the engineered bone tissues function similar to native bone," Shih said.

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

Explore further: Changing the environment within bone marrow alters blood cell development

More information: Yu-Ru Shih el al., "In vivo engineering of bone tissues with hematopoietic functions and mixed chimerism," PNAS (2017). www.pnas.org/cgi/doi/10.1073/pnas.1702576114

Related Stories

Changing the environment within bone marrow alters blood cell development

February 22, 2017
Researchers at the University of Illinois report they can alter blood cell development through the use of biomaterials designed to mimic characteristics of the bone marrow.

New findings may help overcome hurdle to successful bone marrow transplantation

May 28, 2013
Blood diseases such as leukemia, multiple myeloma, and myelodysplasia can develop from abnormal bone marrow cells and a dysfunctional bone marrow microenvironment that surrounds these cells. Until now, researchers have been ...

New finding on the formation of fat tissue in man

July 16, 2015
While all red and white blood cells derive from stem cells in the bone marrow, the scientific community has been divided over whether bone marrow cells are also able to produce other cell types. In the present study, the ...

Researchers develop new strategy to limit side effects of stem cell transplants

August 15, 2016
Scientists in Germany have developed a new approach that may prevent leukemia and lymphoma patients from developing graft-versus-host disease (GvHD) after therapeutic bone marrow transplants. The researchers describe the ...

Blood stem cells study could pave the way for new cancer therapy

March 10, 2016
People with leukaemia could be helped by new research that sheds light on how the body produces its blood supply.

Dose of transplanted blood-forming stem cells affects their behavior

May 25, 2016
Unlike aspirin, bone marrow doesn't come with a neatly printed label with dosage instructions. However, a new study published in Cell Reports provides clues about how the dose of transplanted bone marrow might affect patients ...

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.