Saito N, Washio A, Miyashita K, Wahlberg LU, Emerich DF, Morotomi T, Nishihara T and Kitamura C
Objective: Cells that are encapsulated into immunoprotective and implantable devices provide a means of enabling targeted, longterm, continuous, de novo synthesized delivery of very high levels of therapeutic molecules. In this study, we examined effects of polymer encapsulated glial cell line-derived neurotrophic factor (GDNF) secreting ARPE-19 cells on the in vitro viability of odontoblast-like cells (KN-3 cells) under normally lethal starvation conditions. Materials and methods: Devices (polymeric hollow fibers) were loaded with either GDNF-secreting ARPE-19 cells (GDNF-device) or non-modified ARPE-19 cells (ARPE-control device). KN-3 cell survival and function was quantified under starvation conditions when the cells were co-cultured with either control or GDNF devices. We further examined the specificity of GDNF by neutralizing the activity of GDNF with the soluble GDNF receptor (GFRα-1). Results: When KN-3 cells were co-cultured with either device under starvation, the cells exhibited a concentration gradient-dependent enhancement of survival in the area immediately surrounding the device. Similar survival benefits occurred when KN-3 cells were cultured in media previously used to maintain the cells encapsulated in the device. Because ARPE-19 cells also normally secrete low levels of VEGF, the maintenance medium from each device group was pretreated with soluble Flt-1 or soluble GFRα-1 to neutralize VEGF or GDNF. The survival of KN-3 cells was suppressed when cultured in VEGF-neutralized medium from ARPE-control devices, but not in that from GDNF-devices. In contrast, when GDNF was neutralized with soluble GFRα-1, the survival of KN-3 cells was intensely suppressed. Conclusion: These results suggest that GDNF delivered from encapsulated cells can augment the survival of odontoblast-like cells, and that the delivery of growth factors by encapsulated cells may be useful for enhancing pulp wound healing and regeneration. These data also pave the way for additional in vivo studies to determine the utility of this approach in regenerative endodontics.
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