Engineered Biomaterials Enable Cell Replacement Therapy to Restore Motor Function in Parkinson's Disease Model Rats Conference: AIChE Annual MeetingYear: 2017Proceeding: 2017 AIChE Annual MeetingGroup: Student Poster SessionsSession: Undergraduate Student Poster Session: Food, Pharmaceutical, and Biotechnology Time: Monday, October 30, 2017 - 10:00am-12:30pm Parkinsonâs Disease (PD) is a progressive neurodegenerative disease affecting ~10M patients worldwide. One of the hallmarks of PD is the selective loss of midbrain dopaminergic neurons (mDA) residing in the substantia nigra (SN) and projecting to the striatum. The associated loss of striatal dopamine input causes the characteristic debilitating motor dysfunction seen in PD patients. Medications such as levodopa treat PD symptoms by providing a dopamine precursor to help remaining mDA neurons compensate for dying neuronsâ dopamine production; however, since neurodegeneration is not halted, this compensation requires higher amounts of levodopa as degeneration continues, and is still only sufficient for 5-10 years. Deep brain stimulation, an experimental late-stage treatment, risks infection, hemorrhage, and adverse mental side effects due to its invasive, poorly-understood nature. Human pluripotent stem cell (hPSC)-based cell replacement therapy is a promising alternative to existing PD treatments, as it replaces lost mDA neurons and has potential to restore lost function. Previous work in the Schaffer lab has shown that 3D biomaterials including PEG-pNIPAAM and hyaluronic acid hydrogels can aid in overcoming CRTâs key barriers of scalability, differentiation efficiency, and post-transplantation survival. In this experiment, hPSCs were first differentiated into mature mDA neurons using 3D PEG-pNIPAAM gels, then encapsulated in HA-based gels optimized for controlled release of incorporated neurotrophic and dispersion factors, and finally transplanted into the striatum of PD model rats. Two behavioral assays showed rapid and sustained restoration of motor function in the â3DGFâ group, which received mDA neurons grown in PEG-pNIPAAM and encapsulated in the HA gels with incorporated factors. Immunohistochemistry showed improved survival of transplanted neurons, higher proportion of TH+ (mDA) neurons, and increased formation of synapses with host neurons in the 3DGF group, corroborating the improvement in motor function. This sustained functional improvement was not recapitulated in groups where cells were encapsulated without factors, were not HA-encapsulated, or were not cultured in PEG-pNIPAAM. The incorporated neurotrophic/dispersion factors were particularly important, since encapsulation with the factors yielded a 5-fold higher fraction of TH+ neurons than without the factors, and markedly improved motor recovery. Indeed, the two histological measures which correlated best with motor improvement were dispersion of transplanted cells and number of surviving TH+ neurons--both of which were highest in the 3DGF group. These results prove hPSC-based cell replacement therapy is capable of restoring motor function in PD model rats, and is significantly improved by our biomaterial platforms for mDA differentiation and transplantation.