Migration capacity of human umbilical cord mesenchymal stem cells towards glioma in vivo

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Date: Aug. 5, 2013
From: Neural Regeneration Research(Vol. 8, Issue 22)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Article
Length: 5,571 words
Lexile Measure: 1740L

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Byline: Cungang. Fan, Dongliang. Wang, Qingjun. Zhang, Jingru. Zhou

Research Highlights (1) Human umbilical cord mesenchymal stem cells displayed potent glioma-specific targeting capability and extensive distribution in the tumor bed, indicating that ventricular administration may serve as a less invasive administration route compared with intratumoral injection.

(2) The inherent glioma-targeting tropism of human umbilical cord mesenchymal stem cells implies their potential application as a cellular vehicle for the delivery of therapeutic agents in glioma therapy.

Abstract

High-grade glioma is the most common malignant primary brain tumor in adults. The poor prognosis of glioma, combined with a resistance to currently available treatments, necessitates the ment of more effective tumor-selective therapies. Stem cell-based therapies are emerging as novel cell-based delivery vehicle for therapeutic agents. In the present study, we successfully isolated human umbilical cord mesenchymal stem cells by explant culture. The human umbilical cord senchymal stem cells were adherent to plastic surfaces, expressed specific surface phenotypes of mesenchymal stem cells as demonstrated by flow cytometry, and possessed multi-differentiation potentials in permissive induction media in vitro. Furthermore, human umbilical cord mesenchymal stem cells demonstrated excellent glioma-specific targeting capacity in established rat glioma models after intratumoral injection or contralateral ventricular administration in vivo. The excellent glioma-specific targeting ability and extensive intratumoral distribution of human umbilical cord mesenchymal stem cells indicate that they may serve as a novel cellular vehicle for delivering therapeutic molecules in glioma therapy.

INTRODUCTION

Glioblastoma, the most common malignant primary brain tumor in adults, represents an important cause of cancer-related mortality in patients[1]. Although its incidence rate is only 3.19 per 100 000 people[2], it remains the cause of approximately 13 000 cancer-related deaths in the United States annually[3]. The aggressive growth manner, terized by marked angiogenesis and sive tumor cell invasion into normal brain renchyma with frequent formation of tumor microsatellites at distal sites, makes eradication impossible even after extensive microsurgical resection combined with current standard chemoradiation and adjuvant temozolomide[4]. Without treatment, most patients will die within 3 months after diagnosis[5].

Even with the above-mentioned standard therapy, the median survival of newly-diagnosed glioblastoma patients is 14.6 months[4] and the overall survival rate is 9.8% at 5 years, while with radiotherapy alone it is only 1.9%[6]. Moreover, almost all glioblastomas will eventually relapse and survival following disease progression is estimated to be 25-30 weeks[7],[8]. Thus, novel therapeutic strategies must to be investigated for the development of a more effective treatment strategy.

In seeking new therapeutic options, current efforts have focused on exploiting the fact that glioblastomas are highly vascularized tumors characterized by activation of multiple proangiogenic signaling pathways and overexpression of a variety of proangiogenic factors[9]. Consequently, new drug regimens are being developed to target angiogenesis in an attempt to arrest tumor growth. In particular, the novel antiangiogenic agent bevacizumab (Avastin), which targets vascular endothelial growth factor, has been used for glioblastoma treatment[10] and received accelerated Food and Drug Administration approval for use in patients with recurrent glioblastoma in 2009[11]. Bevacizumab has shown promising results with prolonged progression-free survival and favorable consequences...

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Gale Document Number: GALE|A383570295