Mesenchymal stem cells inhibited development of lung cancer induced by chemical carcinogens in a rat model.

Mesenchymal stem cells (MSCs) may play a significant role in carcinogenesis; however, data have shown that MSCs can both promote and inhibit tumor growth. We investigated the effect of MSCs on the development of lung cancer in a rat model. Bone marrow-derived MSCs were isolated from male Wistar rats and fluorescently labeled. Genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) were instilled into the left lung lobes of female rats to induce tumors. Labeled male MSCs were infused into the female rats via tail vein, and the rats were sacrificed on days 3 and 7. MSC survival and distribution were detected by PCR and fluorescence, respectively. Labeled MSCs aggregated at the injection site in the left lobe (MCA/DEN-treated) on day 3 but not the untreated right lobe. Survival of the MSCs in vivo was confirmed by detection of the male SRY gene in lung tissues by PCR at day 3; however, by day 7, lung tissues were SRY-negative. Next, carcinogen-treated rats were divided into two groups and infused with normal MSCs (experimental group) or PBS (control group) every week for 10 weeks, then sacrificed. Cell proliferation in lung tissues was calculated by Ki67 and PCNA expression. Eighty-percent (8/10) of rats in the control group had tumors, while none of the rats in the experimental group had tumors. There was no difference in cell proliferation in lung tissues between the groups. Therefore, bone marrow-derived MSCs prevented development of carcinogen-induced lung cancer in a rat model. Additional studies are needed to determine mechanism.