A toxicity study of multiple-administration human umbilical cord mesenchymal stem cells in cynomolgus monkeys.

Therapies based on stem cells have shown very attractive potential in many clinical studies. However, the data about the safety of stem cells application remains insufficient. The present study was designed to evaluate the overall toxicology of human umbilical cord mesenchymal stem cells (hUC-MSCs) in cynomolgus monkeys with repeated administrations. hUC-MSCs were administered by intravenous injection once every 2 weeks for 6 weeks. The dose levels employed in this study were 2×10(6), 1×10(7) cells/kg body weight. Toxicity was evaluated by clinical observations (body weight, body temperature, and ophthalmology exams), pathology (blood cell counts, clinical biochemistry, urinalysis, and bone marrow smears), immunologic consequences (lymphoproliferation assay, the secretion of interferon-γ and interleukin-4, the percentage of CD3, CD4, CD8 T cells, and the ratio of CD4 and CD8 T cells) and anatomic pathology. Pharmacodynamics in blood and distribution of hUC-MSCs in the tissues of cynomolgus monkeys were measured by real-time polymerase chain reaction. All animals survived until scheduled euthanasia. No stem cells transplantation-related toxicity was found in this study. hUC-MSCs could be found in the blood of cynomolgus monkeys beyond 8 h. The findings of this 6-week toxicity study showed that the transplantation of hUC-MSCs did not affect the general health of cynomolgus monkeys.