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Updated: May 21, 2026
Transpupillary-Guided Trans-Scleral Transplantation of Subretinal Grafts in a Retinal Degeneration Mouse Model
Published on: January 26, 2024
Behavior of Transplanted Multipotent Cells after in Vitro Transplantation into the Damaged Retina
S A Sergeev1, Y V Khramova, M L Semenova
1Biology Faculty, Lomonosov Moscow State University.
Abstract:
The use of stem cell technologies in retinal defect reparation therapy has produced beneficial results. Nowadays, numerous protocols exist which provide a neural differentiation of the stem cells transplanted into the retina. However, questions concerning the functional replacement of the missing retinal neurons by transplanted cells thus far remain unanswered. The organotypic culture protocol was used in this study in order to prove the possibility of transdifferentiation of bone marrow stromal cells (MMSCs) and neural stem/progenitor cells (NSPCs) from EGFP-positive mice and the functional integration of these cells. This technique enables a detailed characterization of cell behavior post-transplantation. Using atomic force microscopy, we reliably demonstrated the difference (p < 0.01) between the thickness of the outgrowths formed by glial and endothelial retina cells and the thickness of neurites and neuro-like transplanted MMSC outgrowths. MMSCs are also shown to form synapses up to 2.5 ± 0.06 µm in diameter on day 4 after the transplantation. Following electrical stimulation (20V, 0.5Hz, 200ms), clear depolarization of retinal neurons and their outgrowths is detected. It is shown that some of these GFP+ MMSCs, which changed their morphology after the transplantation in retinal explants to neuro-like MMSCs, are capable of depolarizing after exogenous stimulation.
Insights
Bone marrow stromal cells (MMSCs) can transform into neuro-like cells and integrate functionally within retinal tissue. These transplanted cells demonstrate synaptic formation and electrical excitability, offering potential for retinal repair therapies.
Area of Science:
- Ophthalmology
- Neuroscience
- Regenerative Medicine
Background:
- Stem cell therapy shows promise for retinal repair.
- Existing protocols achieve neural differentiation but functional integration remains unclear.
- Transdifferentiation of bone marrow stromal cells (MMSCs) for retinal repair is under investigation.
Purpose of the Study:
- To investigate the transdifferentiation potential of MMSCs and neural stem/progenitor cells (NSPCs) in a retinal organotypic culture.
- To assess the functional integration and behavior of transplanted cells post-transplantation.
- To evaluate the neuro-regenerative capacity of MMSCs in a retinal defect model.
Main Methods:
- Organotypic retinal culture from EGFP-positive mice.
- Transplantation of MMSCs and NSPCs.
- Atomic force microscopy for cell morphology and thickness analysis.
- Electrophysiological assessment following electrical stimulation.
Main Results:
- MMSCs successfully transdifferentiated into neuro-like cells within retinal explants.
- Atomic force microscopy revealed distinct differences in outgrowth thickness between native retinal cells and MMSC outgrowths.
- Transplanted MMSCs formed synapses and exhibited depolarization upon electrical stimulation, indicating functional integration.
- Some GFP+ MMSCs demonstrated neuro-like morphology and excitability after transplantation.
Conclusions:
- MMSCs can transdifferentiate into functional, neuro-like cells within the retina.
- These cells integrate and exhibit synaptic activity and electrical excitability, supporting their potential in retinal repair.
- The study provides evidence for the functional replacement of retinal neurons using transplanted MMSCs.
