Abstract |
Adipose tissue stromal vascular fraction contains mesenchymal stem cells, which show protective effects when administered to damaged tissues, mainly through secreted trophic factors. We examined the protective effects of adipose-derived stem cells (ASCs) and ASC- conditioned medium (ASC-CM) against retinal damage and identified the neuroprotective factors in ASC-CM. ASCs and mature adipocytes were isolated from mouse subcutaneous tissue. ASCs were injected intravitreally in a mouse model of light-induced retinal damage, and ASC injection recovered retinal function as measured by electroretinogram and inhibited outer nuclear layer, thinning, without engraftment of ASCs. ASC-CM and mature adipocyte- conditioned medium were collected after 72 hours of culture. In vitro, H2O2- and light-induced cell death was reduced in a photoreceptor cell line with ASC-CM but not with mature adipocyte- conditioned medium. In vivo, light-induced photoreceptor damage was evaluated by measurement of outer nuclear layer thickness at 5 days after light exposure and by electroretinogram recording. ASC-CM significantly inhibited photoreceptor degeneration and retinal dysfunction after light exposure. Progranulin was identified as a major secreted protein of ASCs that showed protective effects against retinal damage in vitro and in vivo. Furthermore, progranulin phosphorylated extracellular signal-regulated kinase, cAMP response element binding protein, and hepatocyte growth factor receptor, and protein kinase C signaling pathways were involved in the protective effects of progranulin. These findings suggest that ASC-CM and progranulin have neuroprotective effects in the light-induced retinal-damage model. Progranulin may be a potential target for the treatment of the degenerative diseases of the retina.
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Authors | Kazuhiro Tsuruma, Mika Yamauchi, Sou Sugitani, Tomohiro Otsuka, Yuta Ohno, Yuki Nagahara, Yuka Ikegame, Masamitsu Shimazawa, Shinichi Yoshimura, Toru Iwama, Hideaki Hara |
Journal | Stem cells translational medicine
(Stem Cells Transl Med)
Vol. 3
Issue 1
Pg. 42-53
(Jan 2014)
ISSN: 2157-6564 [Print] England |
PMID | 24233842
(Publication Type: Journal Article)
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Chemical References |
- Culture Media, Conditioned
- Cytokines
- Granulins
- Grn protein, mouse
- Intercellular Signaling Peptides and Proteins
- Oxidants
- Progranulins
- Hydrogen Peroxide
- Protein Kinase C
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Topics |
- Adipose Tissue
(cytology)
- Animals
- Animals, Outbred Strains
- Cell Culture Techniques
- Cell Death
(drug effects, radiation effects)
- Culture Media, Conditioned
(pharmacology)
- Cytokines
(metabolism)
- Granulins
- Hydrogen Peroxide
(pharmacology)
- Injections, Intraocular
- Intercellular Signaling Peptides and Proteins
(metabolism)
- Light
(adverse effects)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Oxidants
(pharmacology)
- Photoreceptor Cells, Vertebrate
(pathology)
- Progranulins
- Protein Kinase C
(metabolism)
- Retinal Degeneration
(etiology, pathology, therapy)
- Stem Cell Transplantation
(methods)
- Stem Cells
(cytology, metabolism)
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