Conditioned medium from human mesenchymal stem cells (MSC) from different sources induce proliferation or cell death in HepG-2 and Jurkat cancer cells depending on its origin

Abstract

The use of MSCs after cancer treatment present some thoughtful concerns, as their interaction with tumors can enhance tumor cell growth or inhibit its proliferation, depending on the tumor type. To further explore this issue, we analyzed the effect of conditioned media (CM) obtained from cultured MSCs from 3 different sources (adipose tissue (AT), amniotic liquid (AL) and Wharton’s jelly (WJ)) on two cancer cell lines, HepG-2 (hepatocellular carcinoma) and Jurkat (T-cell leukemia) cells. The CMs were collected after 24hs of incubation of sub-confluent MSCs with aMEM containing 20% of FBS. CMs were centrifuged, and passed through 0,22 mm filters and stored at -20 C. CMs from HepG-2, Jurkat cells and MRC-5 normal fibroblast were used as control. Effects of CMs on tumour cell proliferation were tested by MTT assay, in several concentrations after 24 h incubation. Cell cycle of HepG-2 and Jurkat cells treated with 25%, 50% or 75% CM was analysed by cytometry (IP staining) using Modfit LT software. Gene expression of bcl-2, bcl-6, ccnd1, ccnd2 and foxp-1 was assayed by q-PCR of Jurkat. We found that CM from AT enhances HepG-2 and Jurkat cell proliferation. CM from AL led to Jurkat cell proliferation with no effect in HepG2 cells. CM from WJ induced cell dead in Jurkat cells, while increased HepG-2 cell proliferation. MRC-5 CM has no effect on proliferation rate or death of HepG-2 and Jurkat cells. CM from WJ induced increase of ccnd2 and fox-p1 expression in Jurkat cells but not of bcl-2, bcl-6 and ccnd1 expression. CM from AT and AL had no effect. It seems that younger cells, as MSCs from Wharton‘s jelly, can secrete factors that act on differential pathways of death in Jurkat cells. In conclusions, CMs from hMSC led to proliferation or cell death in Jurkat and HepG-2 cell lines depending on the origin of the stem cells. Supported by CNPq, FINEP and INCT