Lopez, Michael, 2015-2016

Michael Lopez
Michael
Lopez

"Correcting Treacher Collins Syndrome Using Patient Derived Neural Crest Stem Cells"

Host Mentor: Michael Longaker, M.D., M.B.A.
Stanford University

Neural Crest Stem Cells (NCSC) are a multipotent population of stem cells that arise from the neural plate border and possess the ability to migrate ventrally throughout the developing embryo. NCSCs retain multipotency prior to migration, during, and after migration, and are capable of differentiating into a variety of cells including cartilage, bone, melanocytes, autonomic neurons, and Schwann cells among others. During development cranial NCSCs migrate into the first and second pharyngeal arch and differentiate into the bones and cartilage that make up the craniofacial structure. Treacher Collins syndrome (TCS) is a rare congenital disorder that has been associated with aberrant expression of NCSCs. Individuals with the syndrome commonly display hypoplasia of the craniofacial structure usually the maxilla, zygoma, and mandible. In severe cases patients may be born without zygomatic arches. In this study we seek to determine whether TCS pathogenesis is due to NCSCs’ inability to differentiate into bone and cartilage. We investigate the NCSCs’ ability to differentiate using TCS patient derived induced pluripotent stem cells (iPSC). The iPSCs are directed toward a NCSC lineage using defined factors and subsequently differentiated into bone and cartilage. This technology may provide an avenue to generate cartilage and bone in vitro from patient derived NCSCs that can then be transplanted back into the patient to help restore craniofacial structure while circumventing graft versus host disease.