On the other hand, limited information is available on the role of CaSR in cell differentiation. Indeed, studies reported to date investigate its involvement in differentiation of specific lineages, such as osteoblasts, osteoclasts, perinatal sympathetic neurons, epidermal initiation sites in mouse developing embryos and epidermic tissues and preadipocytes whereas only few studies reported its role in driving/regulating differentiation of embryonic or fetal-derived stem cells. No studies are reported to date on CaSR role in UCM-MSC differentiation. Investigating whether CaSR affects ostegenic and neurogenic differentiation potency of UCM-derived MSCs by means of its selective agonists could contribute to elucidate differentiation mechanisms and to optimize differentiation protocols and the development of novel targeted therapies in both bone diseases and neurodegenerative disorders. The aim of the present study was to investigate, in the horse as a large animal model, the involvement of CaSR on osteogenic and neurogenic differentiation potency of size-sieved UCM-MSC lines, by testing the in vitro effects of AMG641, a novel Estradiol Cypionate research calcimimetic acting as a CaSR agonist. The CNX-774 proliferation study was performed with the aim to preliminary testing in vitro AMG641 activity on equine fetal adnexa-derived size-sieved UCM-MSCs. A dose-response effect of AMG641 on the proliferation rate of eUCM-MSCs was observed. AMG641 in presence of high o significantly increased cell proliferation in both large and small eUCM-MSCs lines. To the best of our knowledge, this is the first study on the effects of AMG641 on cell proliferation of in vitro cultured cell lines and, more specifically, in fetal-adnexa derived mesenchymal stem cell lines. AMG641 is a research calcimimetic mainly reported to date in studies on calcium homeostasis disorders. Recent studies reported its effect as selective activator of CaSR. Only one study has been reported to date, on the effects of AMG641 on in vivo cell proliferation and reduced or unchanged proliferation rates were observed in cells obtained from parathyroid tissues of five-sixth nephrectomized rats, after the application of a long or short term in vivo administration protocol of AMG641, respectively.