Immune cell model paves the way to help immunocompromised children

Melbourne researchers have successfully engineered human immune cells to model an infection common among immunocompromised children in a breakthrough discovery, paving the way for new drug tests and treatments.

The research, led by the Murdoch Children’s Research Institute and published in Stem Cell Reports, used cutting-edge stem cell technology to better understand how infection invades immune cells and causes health complications, such as infections of lung, skin and soft tissues, in immunocompromised people. people, especially those with cystic fibrosis.

Murdoch Children’s researcher Dr Shicheng Jacky Sun said the type of immune cell the team created in the lab, known as a macrophage, played an important role in infection, inflammation and regeneration But because of this function it was also a natural host for germs.

“Using our immune cells made from stem cells, we successfully infected them with a germ called mycobacteria. We were able to see where these mycobacteria live inside human immune cells and the immune reactions they triggered,” he said.

“We were also able to use our stem cell model to rapidly test and screen different types of antibiotics against mycobacteria.”

Dr Sohinee Sarkar, a researcher at Murdoch Children’s, said the search for effective treatments had so far been hampered by a lack of infection models to test new drugs.

“Mycobacteria opportunistically infect people with lung disease, such as cystic fibrosis, and also cause skin and soft tissue infections in those who are immunocompromised,” he said.

“Current treatments take months and involve giving cocktails of different antibiotics with very different toxicities. Treatments often fail as the infection is highly resistant to antibiotics, leaving infected people with few other options. Patients with mycobacteria are also excluded from receiving life-saving lung transplants.

Dr. Sarkar said that because of the high rates of treatment failure, repeated cycles of infection could severely damage lung tissue and accelerate the progression of lung failure in people with cystic fibrosis.

“Improved treatments could mean less frequent hospital visits, shorter stays and minimal exposure to toxic antibiotics, which is especially important for children with cystic fibrosis,” he said.

Data show that 11% of children with cystic fibrosis test positive for mycobacteria.

Wade pic2Rachell Regan’s 11-year-old son Wade, who has cystic fibrosis, developed an infection caused by mycobacteria a year ago.

Rachell said that despite trying several antibiotic treatments, none had cleared the infection.

“His infection is very resistant to antibiotics and none of the treatments have improved his condition,” he said. We just tried eight weeks of three different antibiotics, all of which failed, and now he’s trying four types, either IV, tablet, or inhaled.

“Since Wade got this infection, his lung function is down to 63 percent, and that’s going to keep getting worse if we can’t get through it. It’s hard when you’re doing everything you can and nothing seems to be working.”

In addition to the antibiotic treatment, which includes wearing a bag around his waist to help infuse the medication into his body, Wade has two physical therapy sessions a day and a nurse visits him every day at school.

Wade and mum Rachell photo 3Rachell said the recent Murdoch Children’s research gave her hope that a successful treatment could be found.

“The stem cell results are very reassuring that one day the right treatment will be discovered, which will change the lives of Wade and other children who not only have severe lung disease but also have to fight infections.” he said.

Dr Sarkar said the infection model could also be used for drug screening for other superbugs with limited treatment options.

“Some bacteria have evolved to escape our immune system by hiding inside host cells, making it difficult to treat these infections with traditional antibiotics,” he said. Our stem cell-based infection model can be easily extended to screen a large number of drugs against these bacteria to identify new treatments.”

Reference: Sun S, See M, Nim HT, et al. Human pluripotent stem cell-derived macrophages harbor Mycobacterium abscessus infection. Stem cell reception. 2022;0(0). doi:10.1016/j.stemcr.2022.07.013

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