AUTOLOGOUS BRAIN SOURCES FOR PERSONALIZED CELL THERAPY IN NEUROLOGICAL DISEASE
Hu Xu, CleusaDeOliveira, Hon Leong, Susanne Schmid, Paula Foster and Matthew O. Hebb
Department of Clinical Neurological Sciences, Western University, Canada
Abstract
Parkinson's Disease (PD)is the second most common degenerative brain disease, affecting an estimated 7-10 million people worldwide. By replacing lost circuitry and providing chronic biological sources of therapeutic agents to the brain, cell-based therapies are expected to be a game changer for the effective treatment of PD and other neurological diseases. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources. Neurotrophic factors (NTFs) may complement dopamine replacement in PD, and offer a potent new class of cytoprotectivepharmacotherapeutics. Clinical application of NTF therapy has met numerous challenges, including poor blood brain barrier permeability, limited tissue diffusion and rapid intraparenchymal metabolism. For sustained and effective cell therapy, an ideal graft would consist of autologous drug (e.g., dopamine, NTF)-producing cells of central nervous system origin that are well-suited to re-integrate into the host environment following transplantation. We have shown that brain biopsies, safely taken from living PD patients at the time of deep brain stimulation surgery, may be cultured to yield millions of cells, with key merits being both host- and brain-derived progeny, avoiding the difficulties associated with somatic tissue sources and non-self donors. The colocalization of multiple NTFs with progenitor and neural proteins raises the intriguing prospect that these cells may effectively integrate back into the host brain to confer broad and enduring therapeutic function.The favorable handling properties of thesecellsallowprolongedcryostorage and genetic manipulation to produce customized phenotypes. This methodology offers a novel autologous tissue source with prospects to advance personalized cell-based therapies for PD and a host of neurological diseases.