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Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model.

التفاصيل البيبلوغرافية
العنوان: Efficacy and dose-dependent safety of intra-arterial delivery of mesenchymal stem cells in a rodent stroke model.
المؤلفون: Dileep R Yavagal, Baowan Lin, Ami P Raval, Philip S Garza, Chuanhui Dong, Weizhao Zhao, Erika B Rangel, Ian McNiece, Tatjana Rundek, Ralph L Sacco, Miguel Perez-Pinzon, Joshua M Hare
المصدر: PLoS ONE, Vol 9, Iss 5, p e93735 (2014)
بيانات النشر: Public Library of Science (PLoS), 2014.
سنة النشر: 2014
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Intra-arterial (IA) delivery of mesenchymal stem cells (MSCs) for acute ischemic stroke is attractive for clinical translation. However, studies using rat model of stroke have demonstrated that IA MSCs delivery can decrease middle cerebral artery (MCA) flow, which may limit its clinical translation. The goal of this study is to identify a dose of IA MSCs (maximum tolerated dose; MTD) that does not compromise MCA flow and evaluate its efficacy and optimal timing in a rat model of reversible middle cerebral artery occlusion (rMCAo). We sought to determine if there is a difference in efficacy of acute (1 h) versus sub-acute (24 h) IA MSCs treatment after rMCAo. Adult female Sprague-Dawley rats underwent rMCAo (90 min) and an hour later a single dose of MSCs (at de-escalating doses 1 × 10(6), 5 × 10(5), 2 × 10(5), 1 × 10(5) and 5 × 10(4)) was given using IA route. MSCs were suspended in phosphate buffered saline (PBS) and PBS alone was used for control experiments. We measured the percent change in mean laser Doppler flow signal over the ipsilateral MCA in de-escalating doses groups to determine MTD. The results demonstrated that the lowering of IA MSC dose to 1 × 10(5) and below did not compromise MCA flow and hence an IA MSC dose of 1 × 10(5) considered as MTD. Subsequently, 1 h and 24 h after rMCAo, rats were treated with IA MSCs or PBS. The 24 h delivery of IA MSCs significantly improved neurodeficit score and reduced the mean infarct volume at one month as compared to control, but not the 1 h delivery. Overall, this study suggests that the IA delivery of MSCs can be performed safely and efficaciously at the MTD of 1 × 10(5) delivered at 24 hours in rodent model of stroke.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24807059/?tool=EBI; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0093735
URL الوصول: https://doaj.org/article/aa4888015b4a4ff6b110e9e41afb9e26
رقم الأكسشن: edsdoj.4888015b4a4ff6b110e9e41afb9e26
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0093735