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

PLoS One. 2016 May 20;11(5):e0155912. doi: 10.1371/journal.pone.0155912. eCollection 2016.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology*
  • Alzheimer Disease / therapy*
  • Animals
  • Disease Models, Animal
  • Humans
  • Injections, Intra-Arterial
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mice
  • Mice, Inbred C3H
  • Mice, Transgenic
  • Parenchymal Tissue / cytology*
  • Treatment Outcome

Grants and funding

This study was supported by grants received from the Korean Health Technology R&D Project, Ministry of Health and Welfare (HI12C1821), and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, (HI14C3484), Republic of Korea. Three of the co-authors, EHC, SJC, and WIO, are currently employed by the following commercial companies: Samsung Electronics Co., Ltd and MEDIPOST Co., Ltd, respectively. 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.