The application of hyaluronic acid hydrogels to retinal progenitor cell transplantation

Control of retinal progenitor cell (RPC) survival, delivery, and differentiation following transplantation into the retina remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the natural developmental milieu. We describe the use of hyaluronic acid (HA) based hydrogels to encapsulate mouse RPCs and a delivery system for injectable tissue engineering. We selected HA because of its role in early development and as a feeder layer in stem cell cultures, and the relative ease with which various parameters can be controlled (e.g., hydrogel architecture, mechanics, and degradation). When encapsulated in three-dimensional HA hydrogels, RPCs maintained their undifferentiated state and readily formed neurospheres. These hydrogels were viscous solutions, exhibiting properties ideal for delivery to a subretinal space. The transplants caused very little disruption to the host retinal architecture. Hydrogels were completely degraded and RPCs distributed evenly in the subretinal space by week 3 and expressed the mature photoreceptor marker recoverin. HA hydrogels, with their developmentally relevant composition and malleable physical properties, provide a unique microenvironment for self renewal and differentiation of RPCs for retinal repair.