We present a highly potent cell therapy, based on selected human placental mesenchymal stromal cells, isolated from the fetal placental tissues (f-hPSC). The study follows preliminary results showing that a preparation of mesenchymal stromal cells, containing high proportion of cells from the fetal placental tissues, very successfully mitigate acute radiation syndrome (ARS). Based on these findings we propose a new method for the direct isolation of the highly active fetal human placental stromal cells (f-hPSC) from fresh, as well as bulk cryopreserved intact placental tissues. In a mouse model of ARS, following 8Gy total body irradiation, remote intramuscular or subcutaneous injections of f-hPSC boosted the regeneration of lethally damaged bone marrow with peripheral blood cell lineages recovery, mitigating the acute radiation damage and raising survival from ~10% to over 85%. The treatment boosted the regeneration of the failing hematopoietic system, supporting also ectopic spleen erythropoiesis. f-hPSC were further applied for successful treatment of local radiation skin damages. The f-hPSC treatment was effective in experimental autoimmune multiple sclerosis encephalomyelitis (EAE) and in a mouse model of inflammatory bowel disease (IBD). In ongoing studies with a model of Cohen Diabetes Rat (CDr), intraperitoneally injected f-hPSC highly significantly reversed severe pancreas damages following high sucrose diet resulting in a better glycemic control and a significant improvement of insulin secretion. Further studies are performed to investigate the mechanism of action of the indirect f-hPSC treatments, focusing on the stress induced activation of relevant family of genes and the secretome f-hPSC following their delivery.