RESUMEN
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 × 107/kg, which is 10 times of that in clinical human use.
Asunto(s)
Trasplante de Células Madre Mesenquimatosas/efectos adversos , Células Madre Mesenquimatosas/citología , Cordón Umbilical/citología , Adipogénesis , Animales , Aspartato Aminotransferasas/metabolismo , Recuento de Células Sanguíneas , Peso Corporal , Complejo CD3/metabolismo , Diferenciación Celular , Células Cultivadas , Creatina Quinasa/metabolismo , Femenino , Infusiones Intravenosas , Interleucina-6/metabolismo , Macaca fascicularis , Masculino , Células Madre Mesenquimatosas/metabolismo , Fósforo/sangre , Linfocitos T/citología , Linfocitos T/metabolismo , Pruebas de Toxicidad Crónica , Trasplante HomólogoRESUMEN
BACKGROUND: The establishment of a tree shrew model for systemic lupus erythematosus (SLE) provides a new method to evaluate the pathogenesis of autoimmune diseases. METHODS: Eighty tree shrews were randomly divided into four groups receiving either an intraperitoneal injection of pristane, lipopolysaccharide (LPS), or pristane and LPS, or no injection. Three weeks after injection, the SLE model tree shrews were divided into the model group and the treatment group. Tree shrews in the treatment group and the normal control group were infused with umbilical cord mesenchymal stem cells (UC-MSCs). The cells were labeled with DiR. Two weeks after transplantation, three groups of tree shrews were analyzed for urine protein, serum antinuclear antibodies and antiphospholipid, and inflammatory cytokine antibody microarray detection. The heart, liver, spleen, lung, and kidney were collected from the three groups and subjected to hematoxylin and eosin (HE) staining and detection of renal immune complex deposition. RESULTS: HE staining indicated pathology in the model group. Red fluorescence revealed immune complex deposition in the kidneys from the model group. CONCLUSIONS: The combined intraperitoneal injection of pristane and LPS is the best way to induce SLE pathological changes. The pathological changes improved after UC-MSC treatment.