Human Embryonic Stem Cell-Derived Dopaminergic Neuron Grafts Lead to Functional Recovery in Parkinsonian Rats

Parkinson’s disease, a neurodegenerative disorder, affects 1% of the human population over 60. Approximately 5-10% of the diseased population develop early-onset Parkinson’s disease before 50. Symptoms arise when 60-70% of midbrain dopaminergic (mDA) neurons degenerate, resulting in tremors, muscle rigidity, bradykinesia, and akinesia. Currently no cure is available. Treatments to alleviate these symptoms include dopamine agonists, levodopa (L-DOPA), and deep-brain stimulation (DBS). However, the efficacy of these treatments decreases over time and negative side effects can result; continual use of L-DOPA can lead to dyskinesia, and though DBS has been effective for a subset of patients, it is very invasive.

Recent developments in cell replacement therapy using human embryonic stem cells (hESC) appear to be promising in treating Parkinson’s patients. In this experiment, a Parkinson’s disease model was established to determine the efficacy of cell replacement therapy by injecting 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of Sprague Dawley rats. Pull and rotational behavioral tests were used to confirm Parkinsonian symptoms and motor deficit in the disease model. 250,000 DA neurons derived from hESC were transplanted into the striatum of the disease models. Motor deficit and functional recovery were assessed following transplantation.

Functional recovery was observed through behavioral analyses beginning at four months post-transplantation. Immunohistochemical analysis of grafts, fluorescent microscopy, and stereology were used to confirm and quantify graft survival as well as illustrate negative staining for proliferation and teratoma formation. This study demonstrates the effectiveness of hESC therapy to regenerate depleted mDA neurons in Parkinson’s disease patients.