Screening and optimization of potential injection vehicles for storage of retinal pigment epithelial stem cell before transplantation

Abstract

Retinal pigment epithelial (RPE) cells are highly specialized neural cells that have several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and ultimately the blinding disease agerelated macular degeneration. Subretinal transplantation of stem cell-derived RPE cell suspensions is being explored as a strategy to recover the damaged retina and improve vision. This approach may be improved by developing a vehicle that increases postinjection cell viability and distribution and integration of RPE cells. In this study, Food and Drug Administration-approved natural polymers, including alginate, methylcellulose, and hyaluronic acid (HA), were examined for performance as cell vehicles for adult human RPE stem cells (RPESCs). We compared the effect of RPESC storage as a cell suspension in these delivery vehicles for 1-96 hr at different temperatures on subsequent cell performance in a cell culture model. RPESC survival, attachment, distribution, proliferation, and differentiation into RPE cells were monitored by microscopy over the course of 8 weeks. Our in vitro results demonstrate that RPESC suspension in a 0.2% HA solution promotes better initial cell distribution, proliferation, cobblestone formation, and expression of RPE cell markers (microphthalmiaassociated transcription factor and orthodenticle homeobox 2) after 96 hr of storage.These data suggest that HA addition to the vehicle can significantly enhance RPESC performance in vitro and is a promising strategy to pursue an improved delivery vehicle supporting in vivo RPE cell transplantation.

Stem Cell Therapy for Retinal Degeneration: The Evidence to Date

“…16,60 Further, stem cells can be modified to overexpress retinal regenerative factors, 31,32,61 and utilization of scaffolds to culture and transplant the stem cells and their derivations might improve their clinical benefits. 62,63 However, there is a lack of consensus on the route of administration, method of evaluation of outcome, source of stem cells, and the long-term effect of stem cell transplantations. Donor-based variations in the functioning of RPE cells derived from iPSCs were observed, 18 which should be considered before transplantation.…”

“… 16 , 60 Further, stem cells can be modified to overexpress retinal regenerative factors, 31 , 32 , 61 and utilization of scaffolds to culture and transplant the stem cells and their derivations might improve their clinical benefits. 62 , 63 …”

Design and Characterization of Biomimetic Kerateine Aerogel-Electrospun Polycaprolactone Scaffolds for Retinal Cell Culture

“…4,12 Moreover, although we have used kerateine as the base layer to mimic choroid, these studies provide preliminary evidence that kerateine is not toxic to RPE cells (ARPE-19) and could therefore be used as carriers of RPE in a fashion similar to those reported for other natural polymers. 34,39 Modulation of the mechanical properties has numerous implications to cell mechanobiology. Examples include impacts on cell differentiation, migration, spreading, proliferation, and gene expression.…”

Plasma polymer surface modified expanded polytetrafluoroethylene promotes epithelial monolayer formation in vitro and can be transplanted into the dystrophic rat subretinal space

“…Whilst the lack of CD11 expression (macrophage) indicates the substrates are well tolerated in the subretinal space of RCS rats, the technical challenge of optimization of injection vehicles for cell‐substrate transplantation still needs to be addressed in both small and large‐eyed globes (Tian et al, 2019). In keeping with the 3 Rs principle involving animal research, we decided additional further animal experimentation in the small eye rodent model would not be performed.…”