Next Article in Journal
New Gene Markers for Metabolic Processes and Homeostasis in Porcine Buccal Pouch Mucosa during Cells Long Term-Cultivation—A Primary Culture Approach
Previous Article in Journal
Crystal Structure of CYP2B6 in Complex with an Efavirenz Analog
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(4), 1026; https://doi.org/10.3390/ijms19041026

Treatment of Arsenite Intoxication-Induced Peripheral Vasculopathy with Mesenchymal Stem Cells

1
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan
2
Department of Orthopaedics, National Yang-Ming University Hospital, Yilan 260, Taiwan
3
Department of Biotechnology and Animal Science, National Yilan University, Yilan 260, Taiwan
4
Department of Pathology, National Yang-Ming University Hospital, Yilan 260, Taiwan
5
Stem Cell Research Center, National Yang-Ming University, Taipei 11221, Taiwan
6
Taipei City Hospital, Taipei 10341, Taiwan
7
Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan
8
Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 3 February 2018 / Revised: 20 March 2018 / Accepted: 26 March 2018 / Published: 29 March 2018
(This article belongs to the Section Molecular Toxicology)
Full-Text   |   PDF [11822 KB, uploaded 3 May 2018]   |  

Abstract

Arsenite (As), a notorious toxic metal, is ubiquitously distributed in the earth and poses a serious threat to human health. Histopathological lesions of As intoxication are known as thromboangiitis obliterans, which are resistant to current treatment and often lead to lower limb amputation. In this study, we attempt to find that treatment with mesenchymal stem cells (MSCs) may be effective for As-induced vasculopathy. We first conducted an in vitro study with a co-culture system containing human MSCs and human umbilical vein endothelial cells (HUVECs) and treated individual and co-cultured cells with various concentrations of arsenite. We also designed an in vivo study in which Sprague Dawley (SD) rats received periodic intraperitoneal (IP) injections of 16 ppm arsenite for 12 weeks. MSCs were harvested from BALB/c mice that were transplanted via tail vein injection. We found that there was significantly higher cellular viability in human mesenchymal stem cells (hMSCs) than in HUVECs under concentrations of arsenite between 15 and 25 μM. The Annexin V apoptosis assay further confirmed this finding. Cytokine array assay for As-conditioned media revealed an elevated vascular endothelial growth factor (VEGF) level secreted by MSCs, which is crucial for HUVEC survival and was evaluated by an siRNA VEGF knockdown test. In the in vivo study, we demonstrated early apoptotic changes in the anterior tibial vessels of As-injected SD rats with a Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, but these apoptotic changes were less frequently observed upon MSCs transplantation, indicating that the cytoprotective effect of MSCs successfully protected against As-induced peripheral vasculopathy. The feasibility of MSCs to treat and /or prevent the progression of As-induced vasculopathy is justified. Further clinical studies are required to demonstrate the therapeutic efficacy of MSCs in patients suffering from As intoxication with vasculopathy. View Full-Text
Keywords: arsenite; peripheral vascular disease; mesenchymal stem cells arsenite; peripheral vascular disease; mesenchymal stem cells
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Chiang, Y.-H.; Lin, C.-C.; Chen, Y.-C.; Lee, O.K. Treatment of Arsenite Intoxication-Induced Peripheral Vasculopathy with Mesenchymal Stem Cells. Int. J. Mol. Sci. 2018, 19, 1026.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top