Mesenchymal Stem Cells as a Therapeutic Treatment for Osteogenesis Imperfecta: Current Understanding Through Clinical Trials

Abstract

Osteogenesis Imperfecta (OI), also known as brittle bone disease, is a rare heterogeneous disorder with an incidence of 1 in 15,000 to 20,000 live births. Currently, OI has been associated with 19 different gene mutations, primarily affecting genes responsible for collagen type I production and resulting in clinical manifestations such as skeletal deformities and a disproportionate, short stature. OI also has associated extra-skeletal defects such as hearing loss, blue sclerae and cardio/respiratory defects. There are many types of OI, resulting in clinical severity from mild to severe based on clinical observations and genetic morphology of the patient. There is currently no cure for OI; however, bisphosphonates remain the only pharmacological off-label treatment for pediatric OI patients. This research paper examines different clinical trials that have occurred since 1999, assessing the use of mesenchymal stem cells as a method of treatment for skeletal defects in severe OI pediatric patients. Possible treatment mechanisms these clinical trials focus on are bone marrow derived mesenchymal stem cell transplants, allogeneic bone marrow derived mesenchymal stem cell engraftments, adeno-associated virus vectors for COL1A1 disruption and human first-trimester fetal blood or fetal liver mesenchymal stem cells. Through research on both adult MSCs and fetal/embryonic MSCs, they have proved to be a feasible, safe and effective therapy for pediatric patients with OI after prenatal and/or postnatal transplantations or infusions. Evidence on mesenchymal stem cells treatments has shown positive and promising benefits, suggesting a better understanding for elongating clinical benefits of long-term post-transplantation.