Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence

Abstract

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.

Amniotic Epithelial Cells: A New Tool to Combat Aging and Age-Related Diseases?

“…Similarly, it was previously shown that transplantation of young mesenchymal stromal cells significantly slows the loss of bone density and prolongs the lifespan of old mice (Shen et al, 2011). We recently reported that the blockade of SASP by AEC-derived conditioned medium delays the onset of senescence in cultured fibroblasts (Di Germanio et al, 2016), consistent with the idea that extrinsic environmental factors can influence cell behavior. Vital organs, tissues, and the in vivo milieu slowly loose some function during aging.…”

“…Injection of AECs into growing tumors reduces their final size through increased activation of a proapoptotic signaling response (e.g., caspase 3 and 8 activity) and reduction in Bcl-2 protein levels (Niknejad et al, 2014). Finally, AEC transplantation blocks tumor proliferation in the G0/G1 phase by inhibiting cyclins (D2, E1, and H) and cyclin-dependent kinases without induction of apoptosis (Magatti et al, 2012; Di Germanio et al, 2016). …”

“…Following transplantation, exogenous stem cells can graft and replace dysfunctional tissues or improve the tissue milieu, possibly through anti-inflammatory and anti-fibrotic mechanisms. Moreover, the AEC secretome contains an array of molecules and proteins capable of replicating most of the properties of AECs (Di Germanio et al, 2016). Although these strategies may ultimately help alleviate some age-related diseases, there are some important caveats that limit the translation of animal studies into clinical trials.…”

Human amniotic epithelial cells inhibit growth of epithelial ovarian cancer cells via TGF-β1-mediated cell cycle arrest

“…Many studies showed that hAECs might be a promising source for cell-based therapy for cancer, because of their ability to induce apoptosis ( 8 ) and stimulating cell cycle arrest ( 19 ). It is known that proliferation of cancer cells depends in part on cell cycle progression ( 20 ).…”

“…It is known that proliferation of cancer cells depends in part on cell cycle progression ( 20 ). hAEC-secreted factors have been shown to have the ability to induce cell cycle arrest in several cancer cells ( 19 , 21 ). However, the specific factors and mechanisms responsible for the cell cycle-regulatory roles of hAECs on cancer cells still remain unclear.…”