Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease

Sadan, O., Shemesh, N., Barzilay, R., Dadon-Nahum, M., Blumenfeld-Katzir, T., Assaf, Yaniv, Yeshurun, M., Djaldetti, R., Cohen, Y., Melamed, E. and Offen, D. 2012. Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease. Experimental Neurology 234 (2) , pp. 417-427. 10.1016/j.expneurol.2011.12.045

Full text not available from this repository.

Abstract

Huntington's disease (HD) is a hereditary, progressive and ultimately fatal neurodegenerative disorder. Excitotoxicity and reduced availability of neurotrophic factors (NTFs) likely play roles in HD pathogenesis. Recently we developed a protocol that induces adult human bone marrow derived mesenchymal stem cells (MSCs) into becoming NTF secreting cells (NTF+ cells). Striatal transplantation of such cells represents a promising autologous therapeutic approach whereby NTFs are delivered to damaged areas. Here, the efficacy of NTF+ cells was evaluated using the quinolinic acid (QA) rat model for excitotoxicity. We show that NTF+ cells transplanted into rat brains after QA injection survive transplantation (19% after 6 weeks), maintain their NTF secreting phenotype and significantly reduce striatal volume changes associated with QA lesions. Moreover, QA-injected rats treated with NTF+ cells exhibit improved behavior; namely, perform 80% fewer apomorphine induced rotations than PBS-treated QA-injected rats. Importantly, we found that MSCs derived from HD patients can be induced to become NTF+ cells and exert efficacious effects similarly to NTF+ cells derived from healthy donors. To our knowledge, this is the first study to take adult bone marrow derived mesenchymal stem cells from patients with an inherited disease, transplant them into an animal model and evidence therapeutic benefit. Using MRI we demonstrate in vivo that PBS-treated QA-injected striatae exhibit increasing T2 values over time in lesioned regions, whereas T2 values decrease in equivalent regions of QA-injected rats treated with NTF+ cells. We conclude that NTF cellular treatment could serve as a novel therapy for managing HD.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: Elsevier
ISSN: 0014-4886
Last Modified: 21 Aug 2019 02:19
URI: http://orca.cf.ac.uk/id/eprint/91871

Citation Data

Cited 46 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item