The human nervous system is incredibly complex. With careful experimental design, we generate simpler models of the brain in the laboratory. Models come in many forms, including using cancer cell lines, primary cells (taken directly from an animal and grown in a dish), and whole animal models. Every model has its strengths and weaknesses, but so far, no model has produced effective drug treatments for most neurodegenerative diseases. Because of this, we have turned to an emerging and exciting new model system that uses human stem cells.
The human stem cells are taken directly from patients. First, patients donate a sample of cells, typically from a skin biopsy or blood draw. The cells are reprogrammed into stem cells using the Yamanaka factors. These cells—termed induced pluripotent stem cells (iPSCs)—are like embryonic stem cells in that they have the potential to become any cell in the human body. We add a variety of growth factors and molecules that mimic specific aspects of human fetal development to turn these iPSCs into adult-like cells. This process, called differentiation, can be directed to create many different types of cells, including brain, heart, or liver cells.
In the TKC, our focus is neurodegenerative diseases. We take iPSCs made from patients with diseases, such as HD, ALS, and PD, and differentiate them into the brain cells affected in these diseases—striatal, motor, and dopaminergic neurons, for example. For these diseases, we’ve shown that patient neurons do not survive as well as those from healthy control volunteers. We’re investigating why this happens, which could uncover clues about the diseases and point to new treatments.
By Jeannette Osterloh, Postdoctoral Fellow: Uncovering mechanisms of C90RF72 toxicity in ALS.