Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology
Shaomei Wang, Bin Lu, Sergei Girman, Jie Duan, Trevor McFarland, Qing-shuo Zhang, Markus Grompe, Grazyna Adamus, Binoy Appukuttan, Raymond Lund, Shaomei Wang, Bin Lu, Sergei Girman, Jie Duan, Trevor McFarland, Qing-shuo Zhang, Markus Grompe, Grazyna Adamus, Binoy Appukuttan, Raymond Lund
Abstract
Background: Retinitis pigmentosa (RP) is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs) to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS) rat, a well-established animal model for RP.
Methodology/principal findings: Animals received syngeneic MSCs (1x10(6) cells) by tail vein at an age before major photoreceptor loss.
Principal results: both rod and cone photoreceptors were preserved (5-6 cells thick) at the time when control animal has a single layer of photoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells) and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs.
Conclusions/significance: These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with minor discomfort. Therefore, MSCs may prove to be the ideal cell source for auto-cell therapy for retinal degeneration and other ocular vascular diseases.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
![Figure 1. Rod and cone protection.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2821411/bin/pone.0009200.g001.jpg)
![Figure 2. Preservation of visual function.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2821411/bin/pone.0009200.g002.jpg)
Figure 3. Vascular protection.
A–F: Retinal whole…
Figure 3. Vascular protection.
A–F: Retinal whole mount was stained with NADPH-diaphorase: A. typical vascular…
Figure 4. Upregulation of trophic factors.
A.…
Figure 4. Upregulation of trophic factors.
A. Semi-quantitative RT-PCR for CNTF, bFGF, BDNF and beta…
Figure 5. Distribution of MSCs.
A. phase…
Figure 5. Distribution of MSCs.
A. phase contrast microphotograph of bone marrow derived mesenchymal stem…
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- Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–1809. - PubMed
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- Research Support, Non-U.S. Gov't
- Animals
- Brain-Derived Neurotrophic Factor / genetics
- Brain-Derived Neurotrophic Factor / metabolism
- Cells, Cultured
- Ciliary Neurotrophic Factor / genetics
- Ciliary Neurotrophic Factor / metabolism
- Disease Models, Animal*
- Gene Expression
- Humans
- Immunohistochemistry
- Mesenchymal Stem Cell Transplantation / methods*
- Rats
- Retina / metabolism
- Retina / pathology
- Retinal Degeneration / complications
- Retinal Degeneration / surgery*
- Retinitis Pigmentosa / pathology
- Retinitis Pigmentosa / surgery
- Reverse Transcriptase Polymerase Chain Reaction
- Treatment Outcome
- Vascular Diseases / complications
- Vascular Diseases / surgery*
- Visual Acuity
- Brain-Derived Neurotrophic Factor
- Ciliary Neurotrophic Factor
- Full Text Sources
- Medical
![Figure 3. Vascular protection.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2821411/bin/pone.0009200.g003.jpg)
![Figure 4. Upregulation of trophic factors.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2821411/bin/pone.0009200.g004.jpg)
Figure 5. Distribution of MSCs.
A. phase…
Figure 5. Distribution of MSCs.
A. phase contrast microphotograph of bone marrow derived mesenchymal stem…
![Figure 5. Distribution of MSCs.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2821411/bin/pone.0009200.g005.jpg)
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Source: PubMed