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Reductions in behavioral deficits and neuropathology in the R6/2 mouse model of Huntington's disease following transplantation of bone-marrow-derived mesenchymal stem cells is dependent on passage number.

Abstract：

INTRODUCTION:Huntington's disease (HD) is an autosomal dominant disorder caused by an expanded CAG repeat (greater than 38) on the short arm of chromosome 4, resulting in loss and dysfunction of neurons in the neostriatum and cortex, leading to cognitive decline, motor dysfunction, and death, typically occurring 15 to 20 years after the onset of motor symptoms. Although an effective treatment for HD has remained elusive, current studies using transplants of bone-marrow-derived mesenchymal stem cells provides considerable promise. This study further investigates the efficacy of these transplants with a focus on comparing how passage number of these cells may affect subsequent efficacy following transplantation. METHODS:In this study, mesenchymal stem cells isolated from the bone-marrow of mice (BM MSCs), were labeled with Hoechst after low (3 to 8) or high (40 to 50) numbers of passages and then transplanted intrastriatally into 5-week-old R6/2 mice, which carries the N-terminal fragment of the human HD gene (145 to 155 repeats) and rapidly develops symptoms analogous to the human form of the disease. RESULTS:It was observed that the transplanted cells survived and the R6/2 mice displayed significant behavioral and morphological sparing compared to untreated R6/2 mice, with R6/2 mice receiving high passage BM MSCs displaying fewer deficits than those receiving low-passage BM MSCs. These beneficial effects are likely due to trophic support, as an increase in brain derived neurotrophic factor mRNA expression was observed in the striatum following transplantation of BM MSCs. CONCLUSION:The results from this study demonstrate that BM MSCs hold significant therapeutic value for HD, and that the amount of time the cells are exposed to in vitro culture conditions can alter their efficacy.

journal_name

Stem Cell Res Ther

journal_title

Stem cell research & therapy

authors

Rossignol J,Fink KD,Crane AT,Davis KK,Bombard MC,Clerc S,Bavar AM,Lowrance SA,Song C,Witte S,Lescaudron L,Dunbar GL

doi

10.1186/scrt545

subject

Has Abstract

pub_date

2015-02-19 00:00:00

pages

issn

1757-6512

pii

10.1186/scrt545

journal_volume

pub_type

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Reductions in behavioral deficits and neuropathology in the R6/2 mouse model of Huntington's disease following transplantation of bone-marrow-derived mesenchymal stem cells is dependent on passage number.