Department of Pathophysiology, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655/76, 323 00, Plzen, Czech Republic.
Laboratory of Neurodegenerative Disorders, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, alej Svobody 1655/76, 323 00, Plzen, Czech Republic.
Cerebellum. 2018 Aug;17(4):428-437. doi: 10.1007/s12311-018-0928-3.
For many degenerative cerebellar diseases, currently, no effective treatment that would substantially restore cerebellar functions is available. Neurotransplantation could be a promising therapy for such cases. Nevertheless, there are still severe limitations for routine clinical use. The aim of the work was to assess volume and morphology and functional impact on motor skills of an embryonic cerebellar graft injected in the form of cell suspension in Lurcher mutant and wild-type mice of the B6CBA and C3H strains after a 6-month survival period. The grafts survived in the majority of the mice. In both B6CBA and C3H Lurcher mice, most of the grafts were strictly delimited with no tendency to invade the host cerebellum, while in wild-type mice, graft-derived Purkinje cells colonized the host's cerebellum. In C3H Lurcher mice, but not in B6CBA Lurchers, the grafts had smaller volume than in their wild-type counterparts. C3H wild-type mice had significantly larger grafts than B6CBA wild-type mice. No positive effect of the transplantation on performance in the rotarod test was observed. The findings suggest that the niche of the Lurcher mutant cerebellum has a negative impact on integration of grafted cells. This factor seems to be limiting for specific functional effects of the transplantation therapy in this mouse model of cerebellar degeneration.
对于许多退行性小脑疾病，目前尚无有效的治疗方法可以显著恢复小脑功能。神经移植可能是此类病例的一种有前途的治疗方法。然而，其在常规临床应用中仍存在严重的局限性。本研究的目的是评估在 6 个月的存活期后，以细胞悬液的形式注入 Lurcher 突变体和野生型 B6CBA 和 C3H 品系小鼠中的胚胎小脑移植物的体积和形态以及对运动技能的功能影响。移植物在大多数小鼠中存活。在 B6CBA 和 C3H Lurcher 小鼠中，大多数移植物严格局限，没有侵入宿主小脑的趋势，而在野生型小鼠中，移植物衍生的浦肯野细胞定植于宿主小脑。在 C3H Lurcher 小鼠中，但在 B6CBA Lurcher 小鼠中，移植物的体积小于其野生型对应物。C3H 野生型小鼠的移植物明显大于 B6CBA 野生型小鼠。移植对旋转棒试验中的表现没有产生积极影响。这些发现表明，Lurcher 突变体小脑的小生境对移植细胞的整合具有负面影响。在这种小脑退行性变的小鼠模型中，这种因素似乎限制了移植治疗的特定功能效果。
