Researchers at the School of Medicine in St. Louis have created a stem cell transplantation approach that does not require radiation or chemotherapy, thanks to their studies on mice.
Instead, the concept uses an immunotherapeutic approach combining targeted removal of blood-forming stem cells from the bone marrow with immune-modulating medications to prevent the immune system from rejecting the new donor stem cells.
A New Approach Could Make Stem Cell Transplants Safer
Stem cells are considered the base of any human body. They keep a lot of secrets that can be explored only by experts. Hence it is necessary for one to store the stem cells which are achieved at the time of birth. They can help one fight many life-threatening diseases also in the future and hence prove highly useful. However, the experts had to face many challenges about moving them and keeping them safe, which issue will be resolved now with the help of technological advancement in this field.
The new technique successfully transplanted stem cells from unrelated mice into mice without causing dangerously low blood cell counts, which are a hallmark of the conventional procedure. The findings also suggested that stem cell transplantation could be useful in the treatment of leukemia.
Because of this study which can be found online in the Journal of Clinical Investigation, more patients with various forms of blood malignancies will be able to benefit from stem cell transplantation. Which may also be considered a treatment for less life-threatening conditions like sickle cell anemia or other genetic abnormalities?
When it comes to blood malignancies that are difficult to cure, stem cell transplantation is the only option. The technique involves replacing the patient’s blood-forming stem cells with those of a donor, thereby eliminating cancer cells from the blood lymph nodes and bone marrow.
“To be able to do a stem cell transplant without having to give radiation or chemotherapy would be transformative,” said senior author and medical oncologist John F. DiPersio. “It could eliminate the dangerously low blood cell counts bleeding complications, organ damage, and infections.
It has particular implications for conducting bone marrow transplantation or gene therapy for patients with noncancerous diseases such as sickle cell anemia where the toxicities of chemotherapy- or radiation-associated conditioning are important to avoid. We have more work to do before we’re ready to translate these findings to people, but we’re encouraged by the results of this study.”
The mice were given immunosuppressive chemicals called Janus kinase inhibitors to prevent the recipient’s immune system from rejecting the donor cells. Baricitinib, a drug licensed by the FDA to treat rheumatoid arthritis, was the primary treatment employed in this trial. They discovered that baricitinib stopped the recipient’s immune cells from targeting the donor stem cells, including T cells and natural killer cells.
They found that the novel procedure struck a balance between donor immune cells targeting leukemia cells called the graft versus leukemia effect and not destroying the recipient’s healthy tissues, a condition known as graft versus host illness.
According to the researchers, the immune dampening medicines prevented the mice in this study from developing graft-versus-host disease, which is another unique and major benefit of this technique.
“By combining the antibody-drug conjugates with JAK inhibitors, we were able to achieve a successful transplant between two completely unrelated strains of mice,” said first author Stephen P. Persaud MD Ph.D. instructor in pathology & immunology. “A successful transplant across such a stringent immunological barrier is promising for eventually being able to harness this technique for patients with leukemia.”
Antibody-drug conjugates and JAK inhibitors can be used together in transplant conditioning, according to DiPersio and Persaud’s patent application.
