Non-invasive stem cell therapy in a rat model for retinal degeneration and vascular pathology

Autor: Bin Lu, Trevor J. McFarland, Markus Grompe, Jie Duan, Grazyna Adamus, Sergei Girman, R. D. Lund, Qing Shuo Zhang, Binoy Appukuttan, Shaomei Wang
Rok vydání: 2009
Předmět:
Retinal degeneration
Pathology
medicine.medical_specialty
genetic structures
medicine.medical_treatment
Visual Acuity
lcsh:Medicine
Gene Expression
Vascular permeability
Biology
Mesenchymal Stem Cell Transplantation
Retina
Neurotrophic factors
Retinitis pigmentosa
medicine
Animals
Humans
Ciliary Neurotrophic Factor
Vascular Diseases
lcsh:Science
Cells
Cultured
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Brain-Derived Neurotrophic Factor
lcsh:R
Mesenchymal stem cell
Retinal Degeneration
Stem-cell therapy
Cell Biology/Cellular Death and Stress Responses
medicine.disease
Immunohistochemistry
Rats
Developmental Biology/Stem Cells
Ophthalmology/Inherited Eye Disorders
Disease Models
Animal
medicine.anatomical_structure
Treatment Outcome
lcsh:Q
Stem cell
Retinitis Pigmentosa
Research Article
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Vol 5, Iss 2, p e9200 (2010)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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