Abstract
Human retinal pigment epithelial (hRPE) cells have been tested as a cell-based therapy for Parkinson's disease but will require additional study before further clinical trials can be planned. We now show that the long-term survival and neurotrophic potential of hRPE cells can be enhanced by the use of FDA-approved plastic-based microcarriers compared to a gelatin-based microcarrier as used in failed clinical trials. The hRPE cells grown on these plastic-based microcarriers display several important characteristics of hRPE found in vivo: (1) characteristic morphological features, (2) accumulation of melanin pigment, and (3) high levels of production of the neurotrophic factors pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A). Growth of hRPE cells on plastic-based microcarriers led to sustained levels (>1 ng/ml) of PEDF and VEGF-A in conditioned media for two months. We also show that the expression of VEGF-A and PEDF is reciprocally regulated by activation of the GPR143 pathway. GPR143 is activated by L-DOPA (1 μM) which decreased VEGF-A secretion as opposed to the previously reported increase in PEDF secretion. The hRPE microcarriers are therefore novel candidate delivery systems for achieving long-term delivery of the neuroprotective factors PEDF and VEGF-A, which could have a value in neurodegenerative conditions such as Parkinson's disease.
Highlights
Parkinson’s disease (PD) is the 2nd most common neurodegenerative disease
Risk for PD is primarily related to increased age, and the most vulnerable neurons are the dopaminergic neurons in the substantia nigra
The Human retinal pigment epithelial (hRPE) cells were seeded onto the microcarriers and followed for 2 months in culture
Summary
Parkinson’s disease (PD) is the 2nd most common neurodegenerative disease. Risk for PD is primarily related to increased age, and the most vulnerable neurons are the dopaminergic neurons in the substantia nigra. Destruction of these neurons leads to a disruption of the pathway between the substantia nigra and striatum and produces a severe dopamine deficiency [1]. Dopamine plays an important role in the communication between the thalamus, striatum, and cortex. Reduction of dopamine levels leads to the cardinal motoric features of Parkinson’s disease: tremor, generalized slowness of movement, and difficulty transitioning from one movement to the [1]. The most effective form of treatment for PD is dopamine replacement therapy
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