Mesenchymal Stem Cells Ameliorate Cerebellar Pathology in a Mouse Model of Spinocerebellar Ataxia Type 1

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disorder caused by the expansion of a polyglutamine tract in the ataxin-1 protein. To date, no fundamental treatments for SCA1 have been elucidated. However, some studies have shown that mesenchymal stem cells (MSCs) are partially effective in other genetic mouse models of cerebellar ataxia. In this study, we tested the efficacy of the intrathecal injection of MSCs in the treatment of SCA1 in transgenic (SCA1-Tg) mice. We found that intrathecal injection of only 3 × 10(3) MSCs greatly mitigated the cerebellar neuronal disorganization observed in SCA1 transgenic mice (SCA1-Tg mice). Although the Purkinje cells (PCs) of 24-week-old nontreated SCA1-Tg mice displayed a multilayer arrangement, SCA1-Tg mice at a similar age injected with MSCs displayed monolayer PCs. Furthermore, intrathecal injection of MSCs suppressed the atrophy of PC dendrites in SCA1-Tg mice. Finally, behavioral tests demonstrated that MSCs normalized deficits in motor coordination in SCA1-Tg mice. Future studies should be performed to develop optimal protocols for intrathecal transplantation of MSCs in SCA1 model primates with the aim of developing applications for SCA1 patients.

Evaluation of the spatial arrangement of Purkinje cells in ataxic rat’s cerebellum after Sertoli cells transplantation

“…Transplantation of some stem cells has been tested in the treatment of ataxia [5,16]. Immunosuppression is required in cell transplantation to prevent rejection of transplanted cells.…”

Infrared light as a potential therapeutic approach for neurodegeneration

“…3 MSCs greatly mitigated the cerebellar neuronal disorganization such as multi-layer arrangement and atrophy of dendrites of Purkinje cells observed in SCA1-transgenic mice [23,24]. Furthermore, MSCs normalized deficits in motor coordination in the SCA1-transgenic mice [23,24].…”

“…Furthermore, MSCs normalized deficits in motor coordination in the SCA1-transgenic mice [23,24]. MSCs even proved effective for attenuation of degeneration of spinal cord of SCA1-knockin (SCA1-KI) mice because MSCs led to a significant suppression of degeneration of both motor neuron axons and myelin sheaths, even 6 months following the MSC injection into SCA1-KI mice [25].…”

Mesenchymal Stem Cells as a Potential Therapeutic Tool for Spinocerebellar Ataxia

“…In contrast to the study above, in which MSCs were injected into the brain parenchyma, MSCs were intrathecally administered to SCA1-Tg mice in our latest study [27]. Mouse bone marrow-derived MSCs significantly ameliorated the ectopic expression of PCs, atrophy of PC dendrites, and progressive motor incoordination observed in the SCA1-Tg mice [27]. In the following sections, we discuss possible mechanisms by which MSCs reduced the degeneration of PCs.…”

“…The intracerebellar transplantation of bone marrow-derived MSCs into the cerebellum improves the motor function of Lurcher mice [25], which are characterized by a spontaneous frameshift mutation in the δ2 glutamate receptor gene [26]. In contrast to the study above, in which MSCs were injected into the brain parenchyma, MSCs were intrathecally administered to SCA1-Tg mice in our latest study [27]. Mouse bone marrow-derived MSCs significantly ameliorated the ectopic expression of PCs, atrophy of PC dendrites, and progressive motor incoordination observed in the SCA1-Tg mice [27].…”