Journal Article

Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

He, Jie, Zhu, Xiang-qing, Yao, Xiang, Pang, Rong-qing, Pan, Xing-hua, Li, Zi-an, Zhao, Jing, Liu, Ju-fen, Ruan, Guang-ping

2017

Overview

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3 + and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 10 7 /kg, which is 10 times of that in clinical human use.

• Publisher: S. Karger AG,Cell Physiol Biochem Press GmbH & Co KG
• Subject: Adipogenesis / Animals / Aspartate Aminotransferases - metabolism / Blood Cell Count / Body Weight / CD3 Complex - metabolism / Cell Differentiation / Cells, Cultured / Chronic toxicity test / Clinical trials / Creatine Kinase - metabolism / Disease / Ethics / Female / Infusions, Intravenous / Interleukin-6 - metabolism / Macaca fascicularis / Male / Mesenchymal Stem Cell Transplantation - adverse effects / Mesenchymal Stem Cells - cytology / Mesenchymal Stem Cells - metabolism / Monkeys & apes / Original Paper / Phosphorus - blood / Preparation / Quality control / Quality identification / Stem cells / T-Lymphocytes - cytology / T-Lymphocytes - metabolism / Toxicity Tests, Chronic / Transplantation, Homologous / Transplants & implants / Umbilical cord / Umbilical Cord - cytology / Umbilical cord mesenchymal stem cells