Intra-Arterially Delivered Mesenchymal Stem Cells Are Not Detected in the Brain Parenchyma in an Alzheimer’s Disease Mouse Model

Na Kyung Lee,Jong Wook Chang,Wonil Oh,Sang Eon Park,Jeongmin Lee,Eun Hyuk Chang,Jehoon Yang,Duk L Na,Soo Jin Choi,Dong-Gyu Jo

doi:10.1371/journal.pone.0155912

Abstract

Mesenchymal stem cells (MSCs) have a promising role as a therapeutic agent for neurodegenerative diseases such as Alzheimer’s disease (AD). Prior studies suggested that intra-arterially administered MSCs are engrafted into the brain in stroke or traumatic brain injury (TBI) animal models. However, a controversial standpoint exists in terms of the integrity of the blood brain barrier (BBB) in transgenic AD mice. The primary goal of this study was to explore the feasibility of delivering human umbilical cord-blood derived mesenchymal stem cells (hUCB-MSCs) into the brains of non-transgenic WT (C3H/C57) and transgenic AD (APP/PS1) mice through the intra-arterial (IA) route. Through two experiments, mice were infused with hUCB-MSCs via the right internal carotid artery and were sacrificed at two different time points: 6 hours (experiment 1) or 5 minutes (experiment 2) after infusion. In both experiments, no cells were detected in the brain parenchyma while MSCs were detected in the cerebrovasculature in experiment 2. The results from this study highlight that intra-arterial delivery of MSCs is not the most favorable route to be implemented as a potential therapeutic approach for AD.

Highlights

Alzheimer’s disease (AD) is the most common form of dementia and the number of individuals affected with AD is rising annually worldwide
To the best of our knowledge, this is the first paper investigating on the delivery of human umbilical cord blood-derived mesenchymal stem cells into the brains of transgenic AD (APP/PS1) and non-transgenic WT (C3H/C57) mice following administration through the intra-arterial (IA) route
The findings of our study indicate that Mesenchymal stem cells (MSCs) cannot be successfully delivered to the brains of WT and AD mice through the IA route

Summary

Introduction

Alzheimer’s disease (AD) is the most common form of dementia and the number of individuals affected with AD is rising annually worldwide. Characterized as a degenerative disease, the symptoms are irreversible, and a definite cure is currently non-existent. IA Delivery of MSCs in an AD Mouse Model. The funders provided support in the form of salaries for authors [EHC, SJC, and WIO], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

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