[LUM#20] My heart has stopped beating
While the heart’s importance is well established, it is often overlooked that the proper functioning of the lungs also depends on a rhythmic movement: that of the multiciliated cells. To treat diseases affecting these essential cells, researchers in regenerative medicine are tracing the life cycle back to its origins.
A bad case of bronchitis and you’re “coughing your lungs out .” While this isn’t exactly pleasant, it does show that your bronchial tubes are working properly; to get rid of dust and germs, they secrete mucus that binds these impurities together. But how do our lungs expel this mucus? “Our bronchi are lined with bronchial epithelium made up of cells whose surfaces are covered with cilia. By fluttering, these cilia direct the mucus so that it moves upward and is expelled,” explains John De Vos, a researcher in regenerative medicine atthe IRMB1. When these multiciliated cells no longer function properly or fail to function at all, the condition is known as primary ciliary dyskinesia (PCD). These are rare and severe conditions that may require a lung transplant.
Modern Alchemy
In an effort to restore the motility of these multiciliated cells, John De Vos and Arnaud Bourdin, a pulmonologist at Montpellier University Hospital, have been working for several years on induced pluripotent stem cells, or iPS cells. “To understand iPS cells, I like to point out that we are made up of differentiated cells, stable over time, which form either skin, bone, liver, or lung tissue, etc.” These cells begin to differentiate starting on the 5th or 6th day of human embryonic development . At this immature stage, we refer to them as pluripotent cells—in other words, cells capable of reproducing indefinitely and differentiating into all the cell types that make up the human body.
Building on the work of Shinya Yamanaka (Shinya Yamanaka, father of pluripotent stem cells, October 8, 2012, Le Monde), winner of the 2012 Nobel Prize, the two researchers from Montpellier have succeeded in reprogramming adult blood cells—which are stable—back to an undifferentiated state; these are known as induced pluripotent stem cells. “Starting with a simple blood sample taken from a patient with ciliary dyskinesia and using a relatively simple technique involving the reactivation of four embryonic genes, we obtain these iPS cells,” explains John De Vos. These iPS cells were then placed for a week in a medium mimicking the embryo’s natural environment and “guided” to develop into lung cells. Under the right conditions, they will produce bronchial epithelium in about 40 days. “Sometimes I use an image from alchemy, but instead of turning lead into gold, we’re turning blood into a bronchus.” ” (Watch John Devos’s lecture on “Reprogrammed Stem Cells to Model the Bronchus” at the 9th Congress of the Association for Medicine, Pharmacy, and Sciences.)
Healthy lungs
Since the goal is to replace the diseased epithelium with new, healthy epithelium, the researchers had to genetically modify the cells affected by DCP. “This work, carried out by Joffrey Mianné as part of his thesis, made it possible to correct the patient’s genetic abnormality in her iPS cell line and create bronchial epithelium capable of beating again. ” To effectively transplant this epithelium, John De Vos and his team will first need to prepare the patient’s bronchi. “If we deposit the repaired cells on the surface of the diseased epithelium, they risk being expelled like any other dust. We will therefore have to scrape it away, proceeding one bronchus at a time, before injecting the new cells. Animal trials will begin in the coming months, with the hope of getting patients’ lungs and hearts beating again within a few years.
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- IRMB (UM, Inserm)
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