A new chance for children after a stem cell transplant

Every year, too many children still die from the consequences of cancer. This may be due to complications following a stem cell transplant. That is why researcher Magdalena Lorenowicz and her team are investigating a promising new therapy that could improve children's chances of survival: treatment with allogeneic mesenchymal stromal cells (MSCs). 

A cancer diagnosis comes as a bolt from the blue. From that moment on, every second counts, and rapid treatment is essential to prevent the cancer from spreading further. Chemotherapy or radiotherapy is not alwaysenough. A stem cell transplant then becomes unavoidable. 

“During a stem cell transplant, diseased stem cells are replaced with healthy stem cells from a donor”, explains Magdalena Lorenowicz, Head of the Advanced In Vitro Models Department at BPRC. “This gives the body a new chance to fight the disease.” 

“The downside of this transplant is that it can cause damage in different parts of the body. This is due to graft-versus-host disease.” 

Fighting healthy stem cells 

Our immune system is designed to recognize and eliminate anything that is foreign. After a stem cell transplant, the donor’s new immune system may recognize the patient’s body as foreign. “You are a match with thedonor’s stem cells to some extent, but never 100 percent.” 

The result? The donor’s immune cells attack healthy cells and tissues in the sick child’s body. This causes a severe inflammatory response known as graft-versus-host disease. “The intestines, liver and skin are particularly vulnerable.” 

“It is a serious condition that affects around 50 percent of children after a stem cell transplant”, Magdalena explains. “The first treatment is to suppress the immune system, reducing the attack by the donor cells. This is usually done with steroids. However, you do not want to suppress the immune system when viruses and bacteria are present because the body still needs to protect itself.” Unfortunately, this treatment does not work foreveryone. “That is why we are working hard to find a solution to this problem.” 

Are MSCs the future? 

Over the past twenty years, extensive clinical research has been carried out into an alternative treatment using allogeneic mesenchymal stromal cells (MSCs). 

“MSCs are cells found in the bone marrow and they have very unique properties”, Magdalena explains. “The immune system is less likely to recognize MSCs as foreign, meaning the body responds less strongly to thedonated stem cells. MSCs also help repair damaged tissue.” 

Research has shown that MSCs suppress immune cells where necessary while supporting the immune system in other parts of the body. “That is the advantage over steroids. Steroids only work in one direction, meaningthe immune system can no longer function properly.” With MSCs, the immune system remains functional. “It almost seems like a miracle treatment”, Magdalena says. 

Finding the best MSC 

“One of the most dangerous forms of graft-versus-host disease affects the intestines. Children develop diarrhea, causing them to lose a great deal of fluid and increasing their risk of death. That is why we focused ourresearch on the intestines”, Magdalena says. 

To investigate whether MSCs can repair damaged intestinal tissue, the researchers used organoids. These are miniature organs that closely resemble the human intestine. The organoids were damaged using busulfan, a chemotherapy drug that is often used in children. MSCs were then added. “We also observed the positive effects of MSCs in the laboratory.” 

At present, MSC therapy is effective in approximately half of the children who receive this treatment. “Of course, we want to increase that percentage.” Magdalena’s goal is to develop a model that can predict in advance which type of MSC should be used for a specific child. 

“If we have data from different donors and understand the molecular profile of the intestine, we can improve MSC therapy and achieve a higher survival rate.”