"Since many chemotherapies used in cancer treatment are neurotoxic, we wondered whether they might also damage sympathetic nerves in bone marrow itself, impairing the ability of hematopoietic cells to regenerate and to manufacture RBCs," said Dr. Frenette. "This possibility hadn't been examined before."
Dr. Frenette and his colleagues treated mice with seven cycles of cisplatin, a common chemotherapy drug with known neurotoxic effects. The cisplatin caused peripheral neuropathy problems similar to those seen in cancer patients. The mice were then given fresh bone marrow transplants to see how well their marrow would regenerate. Despite receiving fresh stem cells, the cisplatin-treated mice had delayed recovery of blood counts compared to controlssuggesting that the prior cisplatin treatments had affected the bone marrow and prevented hematopoietic stem cells from regenerating. By contrast, mice treated with carboplatina non-neurotoxic chemotherapyrecovered their ability to produce blood after bone marrow transplantation.
To confirm that healthy sympathetic nerves in the bone marrow are needed to regenerate hematopoietic stem cells and produce RBCs, the researchers selectively damaged sympathetic nerves in bone marrow using chemicals or genetic engineering. In both cases, the mice with the damaged sympathetic nerves were less able than control mice to recover after bone marrow transplant.
The researchers found that injury to these nerves could be reduced by giving mice nerve-protecting agents along with chemotherapy. Mice treated with seven cycles of cisplatin along with 4-methylcatechol (an experimental drug that reportedly protects sympathetic nerves) showed improved response to bone marrow transplantation, compared to controls.
Dr. Frenette and his collea
|Contact: Kim Newman|
Albert Einstein College of Medicine