The effects of human umbilical cord-derived multipotent mesenchymal stromal cell transplantation in mice of different strains with an experimental model of parkinsonism

Abstract

One of the promising directions of cell therapy for Parkinson's disease/parkinsonism is the transplantation of human umbilical cord-derived multipotent mesenchymal stromal/stem cells (hUC-MMSCs), the effectiveness of which may depend on the recipient's genotype. Purpose – to compare the effect of transplanted hUC-MMSCs on behavior, number of T-lymphocytes and macrophages in the brain and lymphoid organs of mice of different strains with a toxin-induced model of parkinsonism. Methods. Adult (6-7-month-old) male mice of FVB/N (haplotype H-2q) and 129/Sv (haplotype H-2b) strains were administered the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 30 mg/kg (control group), and after 7 days, hUC-MMSCs at a dose of 500,000 cells were transplanted into the tail vein. Behavioral reactions were assessed in the "open field", rigidity and rotarod tests. The relative content of T-lymphocytes and activated macrophages in the brain, as well as the weight of lymphoid organs were determined. Results. Under the influence of MPTP, the number of rearings, hole-peeking, body length and step length decreased; the number of boluses increased in FVB/N and 129/Sv mice, and the number of crossed squares in the open field test also decreased in 129/Sv mice. In the brain of mice of both strains, the content of activated macrophages increased and, in FVB/N mice, the number of T-lymphocytes increased too. The thymus weight decreased in mice of both strains, while the spleen weight decreased only in 129/Sv mice. Under the influence of hUC-MMSCs, the motor activity improved mainly in FVB/N mice, while the emotional activity improved in 129/Sv mice. The manifestations of rigidity decreased in mice of both strains. The content of T-lymphocytes and activated macrophages in the brain of mice from both strains, as well as the thymus weight, corresponded to the values of intact animals. The transplantation of hUC-MMSCs contributed to the survival of FVB/N and 129/Sv mice with the MPTP-induced parkinsonism model. Conclusion. The manifestations of behavioral disorders, changes in the content of T-lymphocytes and activated macrophages in the brain, the weight of lymphoid organs in mice with the MPTP-induced model of parkinsonism, as well as the positive effects of transplanted hUC-MMSCs in such animals largely depend on their H-2 genotype (analogous to the HLA system in humans). The results can provide the basis for the development of personalized cell therapy for parkinsonism using hUC-MMSCs.