PMID- 28957810 OWN - NLM STAT- MEDLINE DCOM- 20171226 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 43 IP - 3 DP - 2017 TI - Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells. PG - 891-904 LID - 10.1159/000481639 [doi] AB - 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 x 107/kg, which is 10 times of that in clinical human use. CI - (c) 2017 The Author(s). Published by S. Karger AG, Basel. FAU - He, Jie AU - He J AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Ruan, Guang-Ping AU - Ruan GP AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Yao, Xiang AU - Yao X AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Liu, Ju-Fen AU - Liu JF AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Zhu, Xiang-Qing AU - Zhu XQ AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Zhao, Jing AU - Zhao J AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Pang, Rong-Qing AU - Pang RQ AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Li, Zi-An AU - Li ZA AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. FAU - Pan, Xing-Hua AU - Pan XH AD - Kunming Key Laboratory of Stem Cell and Regenerative Medicine, Kunming General Hospital of People's Liberation Army, Kunming, China. AD - Stem Cells and Immune Cells Biomedical Techniques Integrated Engineering Laboratory of State and Regions, Kunming, China. AD - Cell Therapy Technology Transfer Medical Key Laboratory of Yunnan Province, Kunming, China. LA - eng PT - Journal Article DEP - 20170929 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (CD3 Complex) RN - 0 (Interleukin-6) RN - 27YLU75U4W (Phosphorus) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.7.3.2 (Creatine Kinase) SB - IM MH - Adipogenesis MH - Animals MH - Aspartate Aminotransferases/metabolism MH - Blood Cell Count MH - Body Weight MH - CD3 Complex/metabolism MH - Cell Differentiation MH - Cells, Cultured MH - Creatine Kinase/metabolism MH - Female MH - Infusions, Intravenous MH - Interleukin-6/metabolism MH - Macaca fascicularis MH - Male MH - Mesenchymal Stem Cell Transplantation/*adverse effects MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Phosphorus/blood MH - T-Lymphocytes/cytology/metabolism MH - Toxicity Tests, Chronic MH - Transplantation, Homologous MH - Umbilical Cord/*cytology OTO - NOTNLM OT - Chronic toxicity test OT - Preparation OT - Quality identification OT - Umbilical cord mesenchymal stem cells EDAT- 2017/09/29 06:00 MHDA- 2017/12/27 06:00 CRDT- 2017/09/29 06:00 PHST- 2017/04/05 00:00 [received] PHST- 2017/07/18 00:00 [accepted] PHST- 2017/09/29 06:00 [pubmed] PHST- 2017/12/27 06:00 [medline] PHST- 2017/09/29 06:00 [entrez] AID - 000481639 [pii] AID - 10.1159/000481639 [doi] PST - ppublish SO - Cell Physiol Biochem. 2017;43(3):891-904. doi: 10.1159/000481639. Epub 2017 Sep 29.