New stem cell research paves the way towards individualized medicine for patients with cystic fibrosis (CF) and other lung diseases. The study, led by The Hospital for Sick Children (SickKids), is the first to successfully use stem cells to produce mature lung cells that could potentially be used to study the disease and test drugs.
Researchers were able to induce human embryonic stem cells to become mature lung cells, that contained a gene, called CFTR that when mutated is responsible for cystic fibrosis (CFTR gene was discovered at SickKids in 1989). They then took the experiment a step further, by using induced pluripotent stem cells derived from the skin of patients with cystic fibrosis. They prompted these stem cells to become lung cells, which contain mutations specific to the patients involved. (Induced pluripotent stem cells are adult cells genetically induced to function like embryonic stem cells.)
Once researchers found that they could create lung cells derived from individual patients they then used a compound that resembles an investigational drug that is currently being tested for cystic fibrosis to see if it would rescue the CFTR gene mutation.
This study shows the major impact stem cell research can have on the field of individualized medicine,” says Dr. Janet Rossant (pictured), Principal Investigator of the study and Chief of Research at SickKids. “It is a promising move toward targeted therapy for patients with cystic fibrosis.”
According to Rossant, if we can generate lung cells derived from a particular patient, then we can test to see if a specific drug will work in that individual patient’s cells. If the drug is effective in vitro, then the next step would be to see if it works on the patient.
Prior to this year, the only therapies available for patients with cystic fibrosis have targeted the symptoms (like infection and digestive disorders) rather than the CFTR gene mutation. “More recently there has been a paradigm shift and now drugs are being developed to target the mutant CFTR specifically,” says Christine Bear, a co-investigator of the study, Co-Director of the SickKids CF Centre and Senior Scientist in Molecular Structure & Function at SickKids. “However, every patient is unique, so one drug isn’t necessarily going to work on all patients with the same disease,” says Bear. “Take cancer as an example, each individual responds differently to each treatment. For some, a certain drug works, and for others it doesn’t. This tells us that we need to be prepared to find the best option for that individual patient.”
In this particular study, the compound used did not work in all of the derived cell lines and according to Bear, who is also Professor in Physiology at the University of Toronto, this finding further emphasizes the need for individualized medicine.
Researchers say the next step is to perfect the method of generating epithelial lung cells, so that the process is more efficient and can be used to investigate other genetic diseases.
Illustration: The Hospital for Sick Children (SickKids).
The Hospital for Sick Children (SickKids) News Release (08/26/12)
University of Toronto News Release (08/27/12)
Abstract (Nature Biotechnology; (08/26/12))