Findings from a recent study published in Ophthalmology Science assessed the safety and efficacy of allogeneic induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) strip transplantation for patients with RPE degeneration.
Give me some background.
Impairment of the RPE due to aging or gene mutations can cause sight-threatening retinal diseases, such as age-related macular degeneration (AMD) and inherited retinal diseases—which are major causes of blindness in developed countries.
While RPE replacement therapy dates back to the 1990s, recently stem cell technologies like embryonic stem cells and iPSC have provided valuable sources of RPE cells for replacement therapies.
Tell me more about stem-cell derived RPE replacement.
Stem-cell-derived RPE cell transplantation has been applied using two major strategies for graft delivery:
- Transplantation of a monolayer sheet of RPE cells with or without a scaffold
- Transplantation of an RPE cell suspension
- Benefits: Less invasive, involving subretinal injection of graft cells
- Drawbacks: Difficulty in visualizing the graft cells during and immediately after surgery and challenges in controlled delivery to the specific target site, which may potentially lead to cell leakage into the vitreous cavity.
- Moreover, scattered subretinal cells can be difficult to locate until they obtain substantial pigmentation and changes at the graft site are difficult to evaluate.
To combine the advantages of these strategies while avoiding their disadvantages, a Japanese research team developed RPE strips via strip-like aggregates of RPE cells prepared by incubating cells in narrow grooves.
And now this novel technique.
In animal models of this technique: After transplantation, the RPE strip expanded with correct apical-basal polarity and successfully formed a monolayer under the retina.
- These RPE strips can be transplanted using a 31-gauge subretinal cannula and are visible during and immediately after surgery, allowing clinicians to monitor subtle changes at the graft site during follow-up.
The novel technique outlined above combines the structural integrity and robust subretinal delivery of the RPE sheet with the minimally invasive nature of the RPE cell suspension.
Bring it back to the study.
In this single-arm, open-label interventional study, researchers included 3 eyes from 3 patients clinically diagnosed with RPE impairment disease, as follows:
- 1 patient had dry AMD
- 2 patients had MER Proto-oncogene, tyrosine kinase (MERTK)-associated retinitis pigmentosa
Main outcome measures: A reduction of abnormal RPE area by grafting transplanted allogeneic iPSC-derived RPE cells—as measured via fluorescein angiography (FA) at baseline and up to 52 weeks post-transplantation.
Findings?
The primary endpoint was achieved in all patients at 53 weeks post-transplantation.
Visual function assessments confirmed significant vision-related quality of life improvement and potential retinal sensitivity restoration in one patient with dry AMD.
Keep going…
The successful subretinal delivery of iPSC-derived RPE strips was confirmed during and immediately after surgery.
The engraftment of RPE cells migrated out from the strips was observed using polarization-sensitive optical coherence tomography (OCT).
- What that looked like: This was visualized as characteristic hexagonal cells via adaptive optics imaging in all patients.
No serious adverse events (AEs) occurred, though suspected immune reactions to graft cells and epiretinal membrane (ERM) formation were observed in one patient each.
Expert opinion?
“One of the three cases showed suspected immune reactions to graft cells 12 weeks after the planned discontinuation of systemic immunosuppressants; however, systemic and focal anti-inflammatory therapies controlled immune reactions, and grafted cells survived,” the study authors highlighted.
Limitations?
The limited number of patients and short follow-up periods were key limitations for this study.
Take home.
These findings suggest that a decrease in abnormal RPE area via delivery of allogeneic iPSC-derived RPE strips was achieved in all three cases with no serious AEs.
For the future: Further long-term studies with larger cohorts and better preoperative vision are warranted to evaluate the safety and efficacy of RPE strip transplantation.