Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.

Juan Bayo,Flavia Piccioni,Guillermo Mazzolini,Mariana Malvicini,Estanislao Peixoto,Marcela Bolontrade,Mariana G Garcia,Manglio Rizzo,Osvaldo Podhajcer,Esteban Fiore,Laura Alaniz,Jorge B Aquino

doi:10.1155/2014/837420

Abstract

Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

Highlights

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide
In accordance with the criteria for defining Mesenchymal stromal cells (MSCs) of the International Society for Cellular Therapy (ISCT) [26], surface marker expression of bone marrow- (BM-)MSCs and human umbilical cord perivascular cells (HUCPVCs) was evaluated by flow cytometry
A higher migratory capacity towards all the Cell conditioned medium (CCM) was found for HUCPVCs when compared to bone marrow MSCs (BMMSCs) (Figure 1(b))

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The development of new therapeutic approaches is critical, and cellular therapy emerges as a new potential strategy to deliver therapeutic genes to HCC. Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of cells that include adult multipotent cells [3]. MSCs are present in adult tissues and their involvement in repair mechanisms has been demonstrated as the result of their ability to migrate towards sites of injury, their capacity to differentiate into tissues of mesodermal origin (adipocytes, BioMed Research International osteoblasts, and chondroblasts), and their immunoregulatory properties [4]. The possibility of expanding these cells in vitro makes them useful tools for therapeutic use in regenerative medicine, immunomodulation purposes and as cellular carriers for therapeutic genes [5]

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