Fat cells in bone marrow impair transplant healing
CHICAGO (Reuters) - Fat cells appear to slow the formation of new blood cells in bone marrow, and trimming them may be a new way to help cancer patients recover faster from bone marrow transplants, U.S. researchers said on Wednesday.
Scientists had thought that clumps of fat cells in bone marrow just took up space, but a team led by Dr George Daley at Children's Hospital Boston and Harvard Medical School said they actually get in the way of blood cell production.
Genetically engineered mice that lacked the ability to make these fat cells in bone marrow were far more efficient at making blood cells, Daley's team reported in the journal Nature.
And tests with experimental fat-blocking compounds appeared to improve their blood-making abilities.
"Our data is really the first to show if you can block the fat, the blood grows back better," Daley said in a telephone interview.
"They make it harder to recover from chemotherapy or radiation because they actively suppress blood production. If we could prevent them from invading the bone marrow, patients might be able to recover faster from marrow and cord-blood transplants."
At birth, bone marrow is filled with blood-making cells, but fat cells gradually invade this space with age.
Daley and colleagues did a series of studies in mice to see what effect these fat cells -- called adipocytes -- had on the process of making new blood cells.
In the relatively fat-rich tail bones, they found only 25 percent as many blood-forming stem cells and up to three times fewer specialized blood-making or progenitor cells than in bones from other parts of the body.
Adding fat cells to a lab dish with blood-forming cells made them less efficient.
Mice treated with compounds that block fat cell formation, or mice genetically incapable of forming fat cells, were faster at building up bone marrow that had been wiped out with radiation.
They were also quicker to make blood cell progenitors, which are especially important for healing right after a bone marrow transplant.
Daley said several experimental compounds known as PPAR gamma antagonists that block fat cell formation might help bone-marrow transplant patients recover faster.
A number of drug companies, including GlaxoSmithKline, AstraZeneca and Bristol-Myers Squibb Co, have various PPAR gamma drugs in development.
One is BMS309403, an experimental fat-blocking drug developed by Bristol-Myers that has shown promise at protecting mice from type 2 diabetes and heart disease.
"We are now testing whether these anti-obesity drugs have a beneficial effect on blood formation in mice," Dr Olaia Naveiras of Children's, who worked on the study, said in a statement.