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, uses cutting-edge stem cell technology to better understand how infection invades immune cells and causes health complications such as lung and skin and soft tissue infections , in immunocompromised 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, plays an important role in infection, inflammation and regeneration. But thanks to this function, it is also a natural host for microbes.
“Using our immune cells created from stem cells, we successfully infected them with a microbe called mycobacterium. We can see where these mycobacteria live in human immune cells and the immune responses they have triggered,” he said.
“We were also able to use our stem cell model to rapidly test and screen different types of antibiotics against mycobacteria.”
Murdoch Children’s researcher Dr Sohini Sarkar 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 diseases, such as cystic fibrosis, and also cause skin and soft tissue infections in those with immune deficiencies,” she said.
“Current treatments take months and involve giving cocktails of different antibiotics with wide-ranging toxicity. Treatment often fails because the infection is highly resistant to antibiotics, leaving infected people with few other options. Patients with mycobacteria are also excluded from life-saving lung transplants.
Dr. Sarkar said that because of the high rate of treatment failure, repeated cycles of infection can significantly damage lung tissue and accelerate the progression of lung failure in those with cystic fibrosis.
“Improved treatment can mean fewer hospital visits, shorter stays and minimal exposure to toxic antibiotics, which is especially important for children with cystic fibrosis,” she said.
Data show that 11 percent of children with cystic fibrosis test positive for mycobacteria.
Wade pic2 Rachell Regan’s son, Wade, 11, who has cystic fibrosis, developed an infection caused by mycobacteria a year ago.
Rachel said that despite trying several antibiotic treatments, none were able to clear the infection.
“His infection is very resistant to antibiotics and none of the treatments have improved his condition,” she said. We’ve just tried eight weeks of three different antibiotics that didn’t work, and now he’s tried four types, taken intravenously, in tablet form, or inhaled.
“Since Wade got this infection, his lung function has dropped to 63 percent, and it’s going to continue to get worse if we can’t get it under control. It’s hard when you’re doing everything you can and nothing seems to be working.
In addition to the antibiotic treatment, which involves wearing a bag around his waist to help infuse the medicine into his body, Wade has twice-daily physical therapy sessions and a nurse visits him every day at school.
Wade and mum Rachel photo 3 Rachel said the recent Murdoch Children’s research gives her hope that a successful treatment will be found.
“The stem cell results are very reassuring that one day the right treatment will be found that will change the lives of Wade and other children who not only have severe lung disease but also have to fight infections,” she said.
Dr Sarkar said the infection model could also be used to screen drugs for other superbugs with limited treatment options.
“Some bacteria have evolved to escape our immune system by hiding in the host’s cells, making it difficult to treat these infections with traditional antibiotics,” she said. Our stem cell-based infection model can be easily scaled up to screen a large number of drugs against such bacteria to identify new treatments.
Reference: Sun S, See M, Nim HT, et al. Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection. Representative of stem cells. 2022;0(0). doi:10.1016/j.stemcr.2022.07.013
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