Porcine epidemic diarrhea virus (PEDV) which was isolated in 2013 in the US is causing huge economic losses to Pork Industry. PEDV causes an acute enteric infection in pigs of all ages but infection is severe in suckling piglets causing up to 90-95% mortality in this age group. Therefore, there is immediate need to device control measures to control both these infections in pigs. A few commercial vaccines were granted conditional license for use in pigs in the US to control PEDV. However, their protective efficacy in field conditions is not known. In this proposal, we attempted to develop live attenuated vaccine by passaging virulent strain of PEDV in mesenchymal stromal (stem) cells (MSCs) isolated from duodenum of newborn piglets. We passaged KS 14-01 strain 40 times (KS-P40) in MSCs and examined the pathogenesis of passaged virus in neonatal pigs and protective efficacy of passaged virus against challenge with virulent field PEDV. Inoculation of KS-P40 in piglets caused mild diarrhea and significantly less virus shedding in the feces as compared to virulent PEDV-inoculated piglets. KS-P40 also induced the production of IgG and IgA antibodies and provided protection against clinical disease and reduced fecal virus shedding upon challenge with virulent field PEDV. Additional passages in MSCs may be required to obtain a complete attenuated live attenuated vaccine for PEDV.