Fate of two types of cerebellar graft in wild type and cerebellar mutant mice

Čedíková, Miroslava; Houdek, Zbyněk; Babuška, Václav; Kulda, Vlastimil; Vožeh, F; Zech, Nicolas H.; Černá, Lenka; Krakorova, Kristyna; Králíčková, Milena; Cendelín, Jan

doi:10.1016/j.jab.2013.03.001

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…Purkinje and bone marrow cells were located (Figure 2a and 2g and S1g), as previously described (Díaz, Recio, et al, 2012;Johansson et al, 2008;Weimann et al, 2003). Purkinje cells with similar features were also identified in other experiments involving direct grafts of neural progenitors into the cerebellum (Cedikova et al, 2014), a result that supports our findings. However, it is necessary to note that this process occurred in neurons that probably had already started to die, exhibiting a small size (even with two nuclei) and a degenerated dendritic tree, as previously described (Baltanás et al, 2013;Inoue et al, 2001;Yoshida et al, 2014).…”

Section: Previous Reports Employing Bone Marrow Ablation (By Radiation)supporting

confidence: 91%

Daily bone marrow cell transplantations for the management of fast neurodegenerative processes

Díaz

Pilar

Carretero

et al. 2019

J Tissue Eng Regen Med

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Cell therapy has been proven to be a promising treatment for fighting neurodegenerative diseases. As neuronal replacement presents undeniable complications, the neuroprotection of live neurons arises as the most suitable therapeutic approach. Accordingly, the earlier the diagnosis and treatment, the better the prognosis. However, these diseases are commonly diagnosed when symptoms have already progressed towards an irreversible degenerative stage. This problem is especially dramatic when neurodegeneration is aggressive and rapidly progresses. One of the most interesting approaches for neuroprotection is the fusion between healthy bone marrow‐derived cells and neurons, as the former can provide the latter with regular/protective genes without harming brain parenchyma. So far, this phenomenon has only been identified in Purkinje cells, whose death is the cause of different diseases like cerebellar ataxias. Here we have employed a model of aggressive cerebellar neurodegeneration, the Purkinje Cell Degeneration mouse, to optimize a cell therapy based on bone marrow‐derived cell and cell fusion. Our findings show that the substitution of bone marrow in diseased animals by healthy bone marrow, even prior to the onset of neurodegeneration, is not fast enough to stop neuronal loss in time. Conversely, avoiding bone marrow replacement and ensuring a regular supply of healthy cells through continuous, daily transplants, the neurodegenerative milieu of PCD is enough to attract those transplanted elements. Furthermore, in the most affected cerebellar regions, more than a half of surviving neurons undergo a process of cell fusion. Therefore, this method deserves consideration as a means to impede neuronal cell death.

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Section: Previous Reports Employing Bone Marrow Ablation (By Radiation)supporting

confidence: 91%

Daily bone marrow cell transplantations for the management of fast neurodegenerative processes

Díaz

Pilar

Carretero

et al. 2019

J Tissue Eng Regen Med

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Transplantation of Embryonic Cerebellar Grafts Improves Gait Parameters in Ataxic Lurcher Mice

et al. 2015

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Hereditary cerebellar ataxias are severe diseases for which therapy is currently not sufficiently effective. One of the possible therapeutic approaches could be neurotransplantation. Lurcher mutant mice are a natural model of olivocerebellar degeneration representing a tool to investigate its pathogenesis as well as experimental therapies for hereditary cerebellar ataxias. The effect of intracerebellar transplantation of embryonic cerebellar solid tissue or cell suspension on motor performance in adult Lurcher mutant and healthy wild-type mice was studied. Brain-derived neurotrophic factor level was measured in the graft and adult cerebellar tissue. Gait analysis and rotarod, horizontal wire, and wooden beam tests were carried out 2 or 6 months after the transplantation. Higher level of the brain-derived neurotrophic factor was found in the Lurcher cerebellum than in the embryonic and adult wild-type tissue. A mild improvement of gait parameters was found in graft-treated Lurcher mice. The effect was more marked in cell suspension grafts than in solid transplants and after the longer period than after the short one. Lurcher mice treated with cell suspension and examined 6 months later had a longer hind paw stride (4.11 vs. 3.73 mm, P < 0.05) and higher swing speed for both forepaws (52.46 vs. 32.79 cm/s, P < 0.01) and hind paws (63.46 vs. 43.67 cm/s, P < 0.001) than controls. On the other hand, classical motor tests were not capable of detecting clearly the change in the motor performance. No strong long-lasting negative effect of the transplantation was seen in wild-type mice, suggesting that the treatment has no harmful impact on the healthy cerebellum.

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Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher Mice

et al. 2018

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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.

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Fate of two types of cerebellar graft in wild type and cerebellar mutant mice

Cited by 3 publications

References 35 publications

Daily bone marrow cell transplantations for the management of fast neurodegenerative processes

Daily bone marrow cell transplantations for the management of fast neurodegenerative processes

Transplantation of Embryonic Cerebellar Grafts Improves Gait Parameters in Ataxic Lurcher Mice

Long-Term Development of Embryonic Cerebellar Grafts in Two Strains of Lurcher Mice

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