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Extracellular Matrix

Next-Generation Bone Marrow Transplants: Removing The Toxicity

Posted on 15 August 2016

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Bone marrow transplantation is currently used as an effective cure for many conditions, but it is high risk and the procedure is highly toxic. Stanford scientists have now developed a new method that reduces the toxicity, and even has promising implications for autoimmune conditions

In order for a bone marrow, or blood stem cell transplantation, to take place the host’s own stem cells within the bone marrow must be destroyed. This is achieved with radiotherapy and chemotherapy, but frequently causes large collateral damage to other organs, along with many unpleasant side effects. 

“The chemotherapy and radiation used for transplant damage DNA and can cause both immediate problems and long-term damage to many tissues in the body. Among the many known toxic side effects, these treatments can cause damage to the liver, reproductive organs and brain, potentially causing seizures and impairing neurological development and growth in children” 

Developing a better strategy

In an effort to improve and evolve this tricky procedure, Stanford researchers attempted to develop a more targeted approach. They began with an antibody for a marker called c-kit present on blood stem cells,  which proved able to deplete numbers in immune compromised mice, but not healthy ones. 

The conventional transplant strategy 

The conventional transplant strategy 

The team then combined the c-kit antibody with an additional agent that blocks inhibitory CD47 activity. Blocking CD47 essentially acts as an activating switch, allowing macrophage immune cells to eat all of the cells now coated with the c-kit antibody. This combination treatment enabled the immune system to deplete its own blood stem cells on its own, clearing them away for the new transplant cells sourced from a donor.  

Optimising safety

In addition to developing a safer method of clearance, the team also improved upon current ‘seeding’ techniques; the process by which new blood stem cells are planted within the bone marrow. Most transplants include some additional donor immune cells, which can cause graft complications and even fatalities. Using novel techniques, this time the scientists purified the donor material to remove all of these excess cells – leaving only stem cells behind.  

The two therapies together present a massively increase in safety, with very few mice experiencing any significant side effects. While this technique is yet to be tested in humans, considering the current mortality rate for bone marrow transplants is unbearably high, the hope is that applying this combination approach to humans could drastically reduce mortality rate. 

“If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20 percent to effectively zero”

Wider implications

This development has large implications for many diseases and fields. Organ replacement could benefit from such a therapy, as could replacing faulty immune systems in patients with rheumatoid arthritis or type 1 diabetes. Finding new ways to modify immune response may enable organ transplant recipients to one day live drug free. 

“The transplanted cells, the donated organ and the patient’s own tissues all learn to coexist. The donor blood stem cells re-educate the immune system of the patient, and the transplanted organ doesn’t get kicked out”

Read more at Stanford Medicine

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