Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence.
Amniotic epithelial cells (AECs) are a class of fetal stem cells that derives from the epiblast and resides in the amnion until birth. AECs are suitable candidates for regenerative medicine because of the ease of collection, their low immunogenicity and inability to form tumors after transplantation. Even though human AECs have been widely investigated, the fact remains that very little is known about AECs isolated from rat, one of the most common animal models in medical testing. In this study, we showed that rat AECs retained stemness properties and plasticity, expressed the pluripotency markers Sox2, Nanog, and Oct4 and were able to differentiate toward the osteogenic lineage. The addition of conditioned medium collected from rat AECs to lipopolysaccharide-activated macrophages elicited anti-inflammatory properties through a decrease of Tnfa expression and slowed tumor cell proliferation in vitro and in vivo. The senescence-associated secretory phenotype was also significantly lower upon incubation of senescent human IMR-90 fibroblast cells with conditioned medium from rat AECs. These results confirm the potential of AECs in the modulation of inflammatory mechanisms and open new therapeutic possibilities for regenerative medicine and anti-aging therapies as well.
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.|Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
Clara
C
Di Germanio
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
Michel
M
Bernier
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
Michael
M
Petr
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.|Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise "G. Caporale", Teramo, Italy.
Mauro
M
Mattioli
Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy.
Barbara
B
Barboni
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
Rafael
R
de Cabo
D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D016922:Cellular Senescence; D017077:Culture Media, Conditioned / Q000737:chemistry*; D004847:Epithelial Cells / Q000166:cytology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism; D010012:Osteogenesis; D010641:Phenotype; D000067996:RAW 264.7 Cells; D051381:Rats; D013234:Stem Cells / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha
Gerotarget; SASP; amniotic epithelial cells; inflammation; senescence; tumorigenesis