A basic problem in CF research is that some of the most severe pathology of the disease occurs in the lung, and the lung tends to be located inside a patient, where it is difficult to study. So, although it is possible to get a small number of lung cells to study by doing a biopsy on a patient, these small numbers of cells just aren't enough for major research efforts. Research using cell grown in a petri dish is a critical component of the process to discover new drugs, and the process requires absolutely huge numbers of cells, far more than could ever possibly be obtained from patients. What to do? Up until now, scientists have had to use imperfect methods like artificially turning on the cystic fibrosis gene in some type of cell that is easy to grow in a dish, but isn't a lung cell. This is certainly better than nothing at all, but is far from a perfect system for studying lung disease. Especially in a disease as complicated as CF, the more closely the cells in the petri dish resemble the actual cells that are causing trouble in the patient, the better the medicines that are discovered using them are likely to be.
Enter stem cell technology. The most simple definition of a stem cell is a type of cell that can either divide and make two identical new cells, or divide and keep one cell as the stem cell and produce another cell (a so-called daughter cell) of a different type. The first kind of stem cell that can help with CF research is called the basal cell, which is actually a type of stem cell that lives in the lung. The basal cell can divide to make more cells just like it, or it can produce the two key types of cells that line the lung. At least, it can certainly do those two things when living in its natural environment (ie, the lung) but until recently it has not been possible to grow basal cells very well in a petri dish--a lot of cells are very particular about where they will grow, and without the right environment they will stop growing and die. Luckily, research in Dr. Rajagopal's lab has identified some tricks that allow basal cells to grow happily in petri dishes and produce lots and lots of daughter cells. In other words, it may soon be possible to take a small biopsy from a patient's lung, and grow that patient's very own basal cells in a dish. If provided with the right cues, the basal cells will start making the other two key lung cell types, too. This provides one way to make very large amounts of lung tissue that is both genetically identical to the patient, and pretty similar in structure to the lining of the lung--that is, an ideal system to use to study CF in the lab.
The second type of stem cell that could potentially revolutionize CF research is called an "induced pluripotent stem cell" or iPS cell for short. These cells are very similar to embryonic stem cells, but are actually artificial stem cells that can be made in the lab from a skin biopsy from a patient. Like embryonic stem cells, iPS cells have the ability to form any cell type in the body--at least theoretically. The main trick with iPS cells is that since they have the potential to form all possible cell types, it is often difficult to get them to focus on forming the cell types that are of particular interest for a particular research problem--in this case, lung cells. Again, Dr. Rajagopal's lab has been leading the way to find the technology to convince the iPS cells to make lung cells, and has made incredible progress--he guesses that in the next year or two, his lab should be able make lung cells from iPS cells routinely and in large numbers. Because iPS cells can easily be made from any patient, this technology provides a second way to make lots and lots of a patient's own lung cells to study.
Right now it's a little tough to say which technology (the basal cells or the iPS cells) will ultimately be the best way for finding CF drugs, but either approach is likely to be so much better than the current technology (technology, which, it should be noted, has already produced some amazing discoveries like Kalydeco). We're all eager to see what a drug-discovery company like Vertex will be able to do once they actually have the right types of cells, derived from actual patients, to work with. Papa Bear and I were so grateful to Dr. Rajagopal for taking the time to talk to us, and for giving us so much hope as parents that the amazing progress in his lab will help find cures for Lemon and all the other patients out there with CF. In the mean time, Dr. Rajagopal asked me to help him by educating people in the CF community about the importance of stem cells, and making sure that everyone I know is out there advocating for stem cell research. So, consider this blog post my first small effort in response to his challenge, and stay tuned...
