[ad_1]
<a rel = "lightbox" href = "https://3c1703fe8d.site.internapcdn.net/newman/gfx/news/2018/twostudiesde.jpg" title = "These images from Cincinnati Children scientists show hematopoietic stem cells ( blood The donor stem cell taken from a mouse treated with the preclinical drug CASIN (low) is depolarized with several colored polarity markers – which gives it a better mobilization potential than the untreated stem cell of the upper image. report in the journal Leukemia Preclinical data shows that CASIN treatment can potentially make bone marrow transplant procedures safer and more effective for patients. Credit: Cincinnati Children & # 39; s ">
These images from Cincinnati Children scientists show hematopoietic stem cells (blood stem cells) from donor laboratory mice. The donor stem cell harvested from a mouse treated with the preclinical drug CASIN (bottom) is depolarized with several colored polarity markers – which gives it a better mobilization potential than the untreated stem cell of the upper image. The report of scientists in the journal Leukemia Preclinical data shows that CASIN treatment can potentially make bone marrow transplant procedures safer and more effective for patients. Credit: Cincinnati Children & # 39; s
Two recent studies in the journal Leukemia presenting a new approach to bone marrow donation and transplantation that preclinical laboratory testing suggests could make the rescue procedure safer and more effective for patients.
Researchers at the Cincinnati Children's Cancer and Blood Disease Institute said their studies demonstrate that the use of an experimental drug called CASIN in laboratory mice improves efficiency during harvesting blood stem cells in donors and toxicity in transplant recipients.
Designed to repair the body's blood collection system in the bone marrow, a stem cell transplant can save lives for people with cancers such as leukemia or those battling immunodeficiency diseases. But preparing patients for a transplant involves using toxic chemotherapy to eliminate the existing and defective blood system. This allows it to be replaced by healthy blood stem cells called hematopoietic stem cells (HSCs).
In addition to the toxicity for patients, the procedure does not always work. Harvesting HSCs from effective donors can be a challenge. And, once transplanted, the cells often do not graft in sufficient numbers to make the patient healthy, according to Yi Zheng, Ph.D., principal investigator on both studies and director of the hematology and biology experiment. Cancer.
Get cells to mobilize
In Leukemia study, Zheng's team rationally designed the drug CASIN. The drug mimics the action of an important gene called CDC42 that helps regulate blood stem cells. Tests on mouse models show that CASIN can effectively mobilize hematopoietic stem cells and promote their exit from the bone marrow. The study indicates that blood stem cells taken from CASIN-treated donor mice have better long-term reconstitution potential after transplant than cells taken from currently used clinical regimens.
In the second study, researchers used CASIN to pre-condition mouse grafts in order to make bone marrow compartments more receptive to new and healthy blood stem cells. To do this, the drug prompts existing blood stem cells to leave the bone marrow and migrate to the peripheral blood, which is found in circulating blood that is not sequestered in the bone marrow. This reduces the amount of chemotherapy needed to condition the bone marrow in transplant recipients. It could allow for effective preconditioning of the transplant when a recipient is unable to tolerate a procedure based on chemotherapy.
"Our data demonstrate that the new CASIN application regimen has the potential to improve both sides of the transplantation practice.It mobilizes high quality hematopoietic stem cells during stem cell harvest and will condition patients. transplanted to increase the efficiency of the transplant ". "This would be a big step forward, especially for the most vulnerable patients who can not stand the toxicity of chemotherapy treatments or who do not respond to current patterns of blood stem cell mobilization."
How it works
CASIN works by modulating the function of the target protein of the CDC42 gene, Cdc42 (cell division control protein 42). In blood stem cells, levels of Cdc42 are tightly controlled and any change in its activity may result in a transient change in the function and movement of HSCs. Zheng and his colleagues explain that the careful control of Cdc42 activity during stem cell donation and bone marrow transplantation produces the following benefits: 1) High quality stem cells harvested from donors and 2 )
Although Zheng stated that the laboratory results establish proof of principle for the new treatment regimen, the researchers recommend that the procedure using CASIN remain in pre-clinical testing. The present study was conducted on human cells, mouse cells and mouse models of bone marrow transplantation. The results of such studies do not always translate into human patients.
Explore more:
No survival benefit with peripheral blood stem cells versus bone marrow
Source link
