Human Mesenchymal Stem Cells Migrate toward Colon Cancer Partially Regulated by HMGB1

Go Hoshino Hiroshi Yagi

doi:10.4172/2157-7013.1000145

Abstract

Although Mesenchymal Stem Cells (MSC) have been explored as a new clinically relevant cell type to repair injured tissue, a number of studies have highlighted the important aspect of MSC therapy. Studies have shown that systemically administered MSCs migrate to sites of malignant tumor. The focus of this study was to identify the mechanism of migration of human MSCs into cancerous tissue. First, the effect of cultured medium from cancer cell lines on modulating the migration of MSCs was evaluated, using seven different human colon cancer cell lines. Interestingly, the secretion level of High Mobility Group Box 1 (HMGB1) protein from each cell line affected the migration capacity of MSCs. In addition, recombinant human HMGB1 increased MSC’s migration capacity in a dose-dependent manner. Finally, 1×106 human MSCs were injected subcutaneously into mice (n=14) with colon cancer tumors that secreted high levels of HMGB1. Bioluminescence live image analysis showed that MSCs surrounded the tumors after injection into these mice through day 6. Immunohistochemical analysis using CD90 as a specific antibody revealed the existence of MSCs in and around the tumors as well as the secretion of local HMGB1 from the tumors detected by anti-HMGB1 antibody. These findings are critical in understanding the role of MSCs in development of solid tumors and further, they offer insight that may be useful in therapeutic application of MSCs in the treatment of malignant tumors.

Highlights

The migration capacity of Mesenchymal Stem Cells (MSC)s, which is considered to be a category of clinically relevant cell type, may be utilized for potential cell-based therapies
Human-derived MSCs, which were isolated from human bone marrow, were cultured in medium composed of D-MEM supplemented with 10% Fetal Bovine Serum (FBS), 0.1mM nonessential amino acids, 1 ng/ml of basic Fibroblast Growth Factor, 100 U/ml penicillin, 100 μg/ml streptomycin
It was reported that the migration capacity of MSC toward tumors is partly regulated by High Mobility Group Box 1 (HMGB1) mediated signaling [41]

Summary

Introduction

The migration capacity of Mesenchymal Stem Cells (MSC)s, which is considered to be a category of clinically relevant cell type, may be utilized for potential cell-based therapies. The migration of MSCs into multiple inflamed or injured tissues has been studied in various models [2,3]. Isolated MSCs from bone marrow have been demonstrated to migrate toward inflamed tissues and affect via direct contact or in a paracrine fashion in the response of inflammatory cells such as macrophages [4,5], dendritic cells [6,7], and T-cells [3,8]. MSCs exist mostly in bone marrow niche [9], and in various peripheral tissues including fat, salivary gland, tendon, skin, muscle, lung, and more recently, intestinal epithelium [10,11,12,13,14,15,16]. The difference in the role of MSCs from these different niches such as bone marrow and perivascular lesions remains to be identified

Methods

Results

Conclusion