Engineered bone with functional marrow. [Image courtesy Varghese lab, UC San Diego]
Shyni Varghese, a bioengineering professor at UC San Diego Jacobs School of Engineering, led a team to develop a bone-like implant to eliminate the pre-treatment radiation that kills stem cells in a patient’s bone marrow to make room for new marrow. The newly engineered bone tissues give donor cells space room to live and grow without having to compete with pre-existing host cells, which means the patient doesn’t have to undergo any radiation.
“We’ve made an accessory bone that can separately accommodate donor cells. This way, we can keep the host cells and bypass irradiation,” said Varghese in a press release.
The engineered bone tissues are created using functional bone marrow that can be filled with donor cells. The researchers implanted the bone tissue under the skin of mice and donor cells were able to survive for at least 6 months while giving the mice new blood cells.
“In the future, our work could contribute to improved therapies for bone marrow diseases,” said Yu-Ru (Vernon) Shih, a research scientist in Varghese’s lab and the study’s first author.
So far, the implants can only benefit those with non-malignant bone marrow diseases, like aplastic anemia, because there wouldn’t be any cancerous cells that need to be killed.
Bone marrow diseases occur when there are problems with how stem cells develop in the blood, according to the U.S. National Library of Medicine. For example, bone marrow doesn’t create enough red blood cells when someone has aplastic anemia.
Bone marrow produces blood cells. A bone marrow transplant is done to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. The stem cells are used to give rise to the different blood cells in the body.
The UC San Diego–developed implants replicate the long bone structures in the body and are made of a porous hydrogel matrix. It has an outer bone compartment and inner marrow compartment. The outer matrix has calcium phosphate minerals where stem cells grown here can differentiate into bone-building cells. The inner matrix holds the donor stem cells and creates blood cells.
The implants matured into bone tissues with a working blood vessel network and bone marrow inside that could create new blood cells when the researchers inserted the implants under mice skin. The implanted marrow had a host and donor blood cell mixture after 4 weeks and the same mix was found circulating after 24 weeks.
Researchers also took stem cells from implanted marrow and put them into a second group of mice that had bone marrow destroyed by radiation. The transplanted cells diffused into the bloodstream.
“We did these experiments to show that the bone marrow cells from the engineered bone tissues function similar to native bone,” said Shih.
“We’re working on making this a platform to generate more bone marrow stem cells. That would have useful applications for cell transplantations in the clinic,” said Varghese.
The research was supported by the National Institutes of Health and California Institute for Regenerative Medicine. It was published online in the journal PNAS.
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