The potential neuroprotective effect of human adipose stem cells conditioned medium against light-induced retinal damage.
Human adipose-derived stem cells (hASCs) are present in adult adipose tissue and have been reported to secrete various factors that have neuroprotective effects. In the present study, we examined whether hASC-conditioned medium (hASC-CM) was effective against experimental degenerative retinal disease. Mature adipocytes (MAs) and hASCs were isolated from human subcutaneous adipose tissue. The isolated hASCs were identified based on their capacity for bone and neural differentiation. The effects of hASC-CM against tunicamycin-, H2O2-, and light-induced retinal photoreceptor damage were evaluated in vitro by measuring cell death. Moreover, we identified various factors present in hASC-CM using antibody arrays. Retinal damage induced in mice by exposure to white light was studied in vivo, and photoreceptor damage was evaluated according to the thickness of the outer nuclear layer and electroretinography results. In addition, the effect of hASC-CM on Akt phosphorylation at Ser473 was confirmed by western blotting. Finally, the effects of the secreted proteins identified in the hASC-CM on light-induced damage were evaluated in vivo. Isolated hASCs differentiated to osteocytes and neurons. hASC-CM protected against tunicamycin-, H2O2-, and light-induced cell death. In addition, hASC-CM inhibited photoreceptor degeneration and retinal dysfunction after exposure to light. Several proteins secreted by hASCs, such as the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the secreted protein acidic and rich in cysteine (SPARC), protected against light-induced damage in vitro and in vivo. The results of the present study showed that hASC-CM has neuroprotective effects against light-induced retinal damage and suggest that hASCs have a therapeutic potential in retinal degenerative diseases via their secreted proteins, without requiring transplantation.
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Sou
S
Sugitani
Kazuhiro
K
Tsuruma
Yuta
Y
Ohno
Yoshiki
Y
Kuse
Mika
M
Yamauchi
Yusuke
Y
Egashira
Shinichi
S
Yoshimura
Masamitsu
M
Shimazawa
Toru
T
Iwama
Hideaki
H
Hara
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000328:Adult; D000368:Aged; D000818:Animals; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008027:Light / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008875:Middle Aged; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000473:pathology; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
D017077:Culture Media, Conditioned
adipose stem cells; conditioned medium; light-induced damage; mesenchymal stem cells; retina; secreted protein acidic and rich in cysteine; tissue inhibitor of metalloproteinase-1