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


RESULTS
Animals received syngeneic MSCs (1x10(6) cells) by tail vein at an age before major photoreceptor loss.


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
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.
Wang
Shaomei
S
Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America. wangsha@ohsu.edu
Lu
Bin
B
Girman
Sergei
S
Duan
Jie
J
McFarland
Trevor
T
Zhang
Qing-shuo
QS
Grompe
Markus
M
Adamus
Grazyna
G
Appukuttan
Binoy
B
Lund
Raymond
R
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051381:Rats; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000150:complications / Q000601:surgery*; D012174:Retinitis Pigmentosa / Q000473:pathology / Q000601:surgery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000150:complications / Q000601:surgery*; D014792:Visual Acuity
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor