人脐带源性多能间充质间质细胞移植对不同品系小鼠帕金森病模型的影响

Q4 Medicine
Iryna Labunets, Tetyana Panteleymonova, Vitalii Kyryk, Olena Toporova, Zoya Litoschenko
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Adult (6-7 months old) male mice of FVB/N (genotype H-2q) and 129/Sv (genotype 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 (500,000 cells) were transplanted into the tail vein. Behavioral reactions were assessed in open field, rigidity, and rotarod tests. The relative content of T-lymphocytes and activated macrophages in the brain was measured by flow cytometry, and the mass of lymphoid organs was determined. Results. Under the influence of MPTP, the number of rearings, \"sniffs into the nest,\" body length, and step length decreased, the number of boluses increased in FVB/N and 129/Sv mice, and the number of squares crossed in the open field test decreased in 129/Sv mice. In the brain of mice from both lines, the content of activated macrophages increased, and in FVB/N mice, the number of T-lymphocytes also increased. 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引用次数: 0

摘要

帕金森氏病或帕金森病的细胞治疗有希望的方向之一是移植各种来源的多能间充质间质细胞,包括人脐带(hUC-MMSCs),其有效性可能取决于受体的基因型。目标。比较移植骨髓间充质干细胞- p对不同系帕金森中毒模型小鼠行为、脑和淋巴器官中t淋巴细胞和巨噬细胞的影响。材料和方法。将FVB/N(基因型H-2q)和129/Sv(基因型H-2b)的成年雄性小鼠(6-7月龄)按30 mg/kg的剂量给药(对照组)1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP), 7 d后将hucc - mmscs(500,000个细胞)移植到尾静脉。行为反应通过开阔场地、刚性和旋转杆试验进行评估。流式细胞术测定大鼠脑内t淋巴细胞和活化巨噬细胞的相对含量,测定淋巴器官的质量。结果。在MPTP的影响下,FVB/N和129/Sv小鼠的产仔次数、“入巢次数”、体长和步长减少,丸数增加,129/Sv小鼠的空地试验中交叉方块数减少。两系小鼠脑内活化巨噬细胞含量均增加,FVB/N小鼠t淋巴细胞数量也增加。两系小鼠胸腺肿块均减少,而脾脏肿块仅在129/Sv小鼠中减少。hUC-MMSCs移植在FVB/N小鼠中主要改善了运动活动,而在129/Sv小鼠中,两系小鼠的情绪活动得到改善,僵硬症状减少。两系小鼠脑及胸腺肿块中t淋巴细胞和活化巨噬细胞的含量与完整动物的值一致。MMSC移植可促进mptp诱导的帕金森模型FVB/N和129/Sv小鼠的存活。结论。mptp诱导的帕金森模型小鼠的行为障碍的表现、脑内t淋巴细胞和活化巨噬细胞含量的变化、淋巴器官的质量,以及移植hUC-MMSCs的积极作用,在很大程度上取决于它们根据H-2系统(类似于人类的HLA系统)的基因型。结果可能为利用多能间充质间质细胞开发针对这种病理的个性化细胞治疗提供基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The effects of human umbilical cord-derived multipotent mesenchymal stromal cells transplantation in mice of different strains with an experimental model of parkinsonism
One of the promising directions in cell therapy for Parkinson's disease or parkinsonism is the transplantation of multipotent mesenchymal stromal cells from various sources, including human umbilical cord (hUC-MMSCs), the effectiveness of which may depend on the recipient's genotype. Objective. To compare the impact of transplanted MMSC-P on behavior, T-lymphocytes, and macrophages in the brain and lymphoid organs of mice from different lines with a toxic model of parkinsonism. Materials and methods. Adult (6-7 months old) male mice of FVB/N (genotype H-2q) and 129/Sv (genotype 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 (500,000 cells) were transplanted into the tail vein. Behavioral reactions were assessed in open field, rigidity, and rotarod tests. The relative content of T-lymphocytes and activated macrophages in the brain was measured by flow cytometry, and the mass of lymphoid organs was determined. Results. Under the influence of MPTP, the number of rearings, "sniffs into the nest," body length, and step length decreased, the number of boluses increased in FVB/N and 129/Sv mice, and the number of squares crossed in the open field test decreased in 129/Sv mice. In the brain of mice from both lines, the content of activated macrophages increased, and in FVB/N mice, the number of T-lymphocytes also increased. The thymus mass decreased in mice from both lines, while the spleen mass decreased only in 129/Sv mice. The transplantation of hUC-MMSCs improved predominantly motor activity in FVB/N mice, while in 129/Sv mice, emotional activity improved, and manifestations of rigidity decreased in mice from both lines. The content of T-lymphocytes and activated macrophages in the brain of mice from both lines, as well as the thymus mass, corresponded to the values of intact animals. MMSC transplantation promoted the survival of FVB/N and 129/Sv mice with the MPTP-induced parkinsonism model. Conclusions. The manifestations of behavioral disorders, changes in the content of T-lymphocytes and activated macrophages in the brain, and the mass of lymphoid organs in mice with the MPTP-induced parkinsonism model, as well as the positive effects of transplanted hUC-MMSCs in these animals, largely depend on their genotype according to the H-2 system (analogous to the HLA system in humans). The results may provide a basis for developing personalized cell therapy for this pathology using multipotent mesenchymal stromal cells.
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来源期刊
Cell and Organ Transplantology
Cell and Organ Transplantology Medicine-Transplantation
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