Effect of human mesenchymal stem cells intracardiac transplantation on superoxide dismutase 1-G93A mice / 中华神经科杂志

ABSTRACT

Objective To study the changes of life span and pathology in superoxide dismutase 1 (SOD1)-G93A mice after intracardiac transplantation of human mesenchymal stem cells (hMSCs).Methods hMSCs were isolated from bone marrow cells obtained from healthy donors and cultured.The purity and morphology were assessed by flow cytometry (FCM).hMSCs (3×10~6) resuspended in 0.2 ml DMEM was injected into the heart of 8 week-old SOD1-G93A mice.In non-transplantion control SOD1-G93A mice, only DMEM was injected.The mice were evaluated for signs of motor deficit with 4-point scoring system previously described by Weydt et al.The age of onset and life span in mice were assessed.The pathological change including number of motor neurons was investigated by Nissl staining.Immunofluorescence staining with specific human nuclear antibody was used to confirm the transplant of hMSCs in mice.Results The onset symptoms in untreated SOD1-G93A mice appeared at (156.56±3.60) days of age and the average life span was (188.32±3.51) days.hMSCs transplantation delayed the onset of ALS type symptoms about 16 days (x~2=10.888, P=0.001) and prolonged the life span about 14 days compared to the untreated SOD1-G93A littermates((202.19±4.09) days vs (188.32±3.51) days, x~2=3.917, P=0.04).The loss of motor neurons in untreated mice was earlier and more severe than in hMSCs transplanted mice.At 20 weeks, the number of motor neurons in transplanted mice was significantly higher than those in untreated mice.Human specific nuclear antigen in brain and spinal cord was detected in transplanted SOD1-G93A mice.Conclusion hMSCs can be implanted for a long-term into central nervous system by intracardiac transplantation and the transplantation can prolong life span, and delay the onset of the disease and motor neuron loss in SOD1-G93A mice.