Preclinical toxicity evaluation of clinical grade placenta decidua stromal cells

Abstract

Background & Aim Placenta-derived decidua stromal cells (DSCs) are being investigated as an alternative to other sources of mesenchymal stromal cells (MSCs) for cellular therapy. DSCs are more effective in treating acute inflammatory diseases in human. This is a safety study of human DSCs in Sprague-Dawley rats and Balb/c mice. Methods, Results & Conclusion Human DSCs (hDSCs) were cultured and expanded from fetal membranes obtained from placentas following caesarean section. 1.5 DSCs x 106/kg were injected i.v. and i.a. to 4 rats, respectively. In mice, DSCs doses ranged from 4-40\u202f×\u202f106 DSCs/kg given i.v. In vivo tracking of human cells were performed using tranduced hDSC with Luciferin gene. Clotting time was recorded on a coagulometer. All DSCs treated rats had normal motility and behavior. Histological examination was normal for heart, lung, liver, spleen and kidneys. Mice treated with DSCs showed no immediate or long-term side effects. None of the mice died or showed acute toxicity or adverse reactions 3- and 30-days following DSCs infusion. Blood biochemistry profiles related to liver, kidney, heart as well as inflammatory indices were not influenced by DSCs infusion. Complete blood count tests were all normal. Coagulation was not affected. Tracking data showed that infused hDSCs moved to the lung and stayed there up to 4 days after infusion. Compared to hMSCs, the hDSCs had better viability, smaller size and stronger clotting in human blood and plasma. DSCs induced coagulation activation markers, TAT and C3a, were decreased by heparin infusion. hDSCs are safe with almost no side effects even with the doses of 40 times higher than are used clinically.