Ph.D., 1986, University of Illinois at Chicago
Professor, Divison of Translation Science and Molecular Medicine
Can transplanted cells repair the brain? This is one area of research in the Steece-Collier laboratory at MSU. There has long been interest in whether cells of the nervous system that die from trauma or disease could be replaced by new ones. While very early attempts at brain cell grafting were unsuccessful, Dr. Elizabeth Dunn in 1917 was the first to show that young rat brain tissue could survive transplantation to another rat. Despite this landmark discovery, little progress was made in the area of neural transplantation over the next fifty years. Renewed interest in the 1970’s, particularly in the field of Parkinson’s disease (PD), led to an explosion of brain cell transplantation research, which continues through today. Promise from animal studies led to initiation of clinical trials. A group of scientists in Sweden (Lindvall et al., 1989) were the first to demonstrate significant improvements in several behavioral measures following grafting of ‘replacement’ neurons to patients with PD. While some patients experienced significant improvement, the overall results from world-wide clinical trials failed to show statistically significance improvement, and some unfortunate side-effects developed in a portion of the patients. Despite the overall failure of the first wave of clinical trials, the rationale of replacing cells lost to disease remains sound. So why has neural transplantation in PD not yet succeeded? In PD, there is a loss of dopamine containing neurons in an area of the brain known as the substantia nigra. These nigral dopamine neurons normally extend their “neuritic” processes to a target brain region known as the striatum. When the striatum experiences a loss
of dopamine, striatal neurons undergo significant remodeling of their anatomical structure. As you can imagine remodeling of the “micro”anatomy of neurons results in rewiring and altered receptivity of the brain to a variety of therapies designed to treat PD. Indeed, evidence from our laboratory suggests that dopamine depletion in PD renders the striatum less receptive to many therapies including neural grafting. Much of the research in the Steece-Collier lab is aimed at understanding the specifics of how the brain “remodels” itself in the face of neurodegenerative disease, how aging effects these processes, and how such changes can be prevented or reversed. Understanding mechanisms involved in brain plasticity changes associated with cell death will allow for the development of improved therapy for individuals suffering from diseases like PD. We use a variety of approaches including stereotaxic brain surgery, examination of motor behaviors, pharmacology, histology (light and electron microscopic approaches), examination of transmitter and protein levels, cell culture, etc.