Alternative new mesenchymal stem cell source exerts tumor tropism through ALCAM and N-cadherin via regulation of microRNA-192 and -218

Ran Kim,Sekyung Oh,Ki-Chul Hwang,Min Young Lee,Jihyun Lee,Sang In Park,Chang Youn Lee,Woochul Chang,Pilseog Kim,Yong-An Chung,Lee-So Maeng,Jongmin Kim,Hojin Lee

doi:10.1007/s11010-016-2909-5

Abstract

Gliomas are the most common type of malignant primary brain tumors. Some treatments of gliomas exist, but they are rarely curative. Mesenchymal stem cells (MSCs) are emerging as potential modes of targeted cancer therapy owing to their capacity for homing toward tumor sites. It has been proposed that MSCs derived from various sources, such as bone marrow, adipose tissue and umbilical cord blood, can be used as cell-based therapy for brain tumors. Here, MSCs obtained from the synovial fluid of osteoarthritis or rheumatoid arthritis patients were investigated as therapeutic candidates. Specifically, we compared migratory and adhesive abilities, as well as expression levels of related genes and microRNA in bone marrow derived-MSCs (BMMSCs), adipose derived-MSCs (ADMSCs), and synovial fluid derived-MSCs (SFMSCs) after treatment with conditioned medium from gliomas. Migration and adhesion of SFMSCs increased through upregulation of the activated lymphocyte cell adhesion molecule (ALCAM) and N-cadherin by microRNA-192 and -218 downregulation, similar to BMMSCs and ADMSCs. Migratory capacities of all types of MSCs were evaluated in vivo, and SFMSCs migrated intensively toward gliomas. These results suggest that SFMSCs have potential for use in cell-based antitumor therapies.

Highlights

Malignant gliomas are the most prevalent type of primary brain tumors affecting the central nervous system [1, 2]
The results of this study indicate that synovial fluid derived-MSCs (SFMSCs) have potential for use as a new therapeutic vehicle for cell-based anticancer therapies based on comparison to the efficiency of other Mesenchymal stem cells (MSCs) lineages
Tumor homing of bone marrow derived-MSCs (BMMSCs), adipose derived-MSCs (ADMSCs), and SFMSCs by glioma-secreted factors was examined and compared using a transwell assay

Summary

Introduction

Malignant gliomas are the most prevalent type of primary brain tumors affecting the central nervous system [1, 2]. Despite recent technological advances in surgical resection, such as complementation with radiotherapy and chemotherapy, such treatment is rarely curative in cases of extremely poor prognosis [3, 4]. Radiotherapy generally results in irradiation of normal brain tissues as well as the target tumor, causing multiple side effects [1]. Chemotherapy has limited effects because most chemicals have difficulty crossing the blood brain barrier [6]. Recent studies have proposed using tumor tropism of mesenchymal stem cells (MSCs) to overcome the limitations of these approaches

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Conclusion