Personalized medicine for cystic fibrosis: establishing human model systems.
With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification.
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts.|Pediatric Pulmonary Medicine, Massachusetts General Hospital for Children, Boston, Massachusetts.
Hongmei
H
Mou
Pediatric Pulmonary Medicine, Massachusetts General Hospital for Children, Boston, Massachusetts.
Karissa
K
Brazauskas
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts.|Pulmonary Critical Care Unit, Internal Medicine and Pediatrics, Massachusetts General Hospital, Boston, Massachusetts.
Jayaraj
J
Rajagopal
D000818:Animals; D001706:Biopsy; D002454:Cell Differentiation; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D009154:Mutation; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D013234:Stem Cells / Q000166:cytology
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
airway and lung cell biology; cystic fibrosis (CF); individualized medicine; induced pluripotent stem cells; organoids; stem cells