Immunotoxicity and Immunomodulatory Effects of Continuous Intravenous Infusion of Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys
LE Xi1,2, ZHANG Yaqi1,2, ZHOU Duanpeng2, ZHANG Quan2, RAO Wei2, WANG Wei2, XIAO Cuihong2, SHI Liang2, HAN Bing2, WU Dongcheng1,2*
This article studies the immunotoxicity and immunomodulatory properties of hUC-MSCs (human umbilical cord mesenchymal stem cells) in cynomolgus monkeys. The different doses of hUC-MSCs (2.0×106 cells∙kg–1 and 2.0×107 cells∙kg–1) were intravenously administered to cynomolgus monkeys for 14 consecutive days. And then, serum IgG concentration was detected in cynomolgus monkeys, anti-hUC-MSCs antibodies, lymphocyte activation and proliferation, changes in T cell subsets, and histological changes in thymus and spleen. The results showed that intravenous administration of hUC-MSCs for 14 consecutive days had no effects on serum IgG concentration in cynomolgus monkeys, and did not stimulate animals to produce anti-hUC-MSCs antibodies. hUC-MSCs significantly inhibited the activation and proliferation of cynomolgus lymphocytes, decreasing the proportion of CD3+ T cells, and stimulated the proliferation and differentiation of Treg cells. Histological examination revealed that some animals developed thymic cortical atrophy and increased spleen lymphagenic center associated with drug administration. The study concludes that the immunotoxicity of hUC-MSCs is extremely low. After intravenous infusion, it does not cause abnormal reactions such as immune rejection in cynomolgus monkeys, suggesting the safety of allogeneic application clinically.
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