Therapy with un-engineered naïve rat umbilical cord matrix stem cells markedly inhibits growth of murine lung adenocarcinoma

Abstract

BackgroundLung cancer remains the leading cause of cancer-related mortality despite continuous efforts to find effective treatments. Data from the American Cancer Society indicate that while the overall incidence of lung cancer is declining, it continues to rise in women. Stem cell-based therapy has been an emerging strategy to treat various diseases. The purpose of this paper is to determine the efficacy of an intrinsic anti-cancer effect of rat umbilical cord matrix stem cells (UCMSCs) on lung cancer.MethodsA mouse syngeneic lung carcinoma model was used to test the basic ability of UCMSCs to control the growth of lung cancer. Lung tumors were experimentally induced by tail vein administration of Lewis lung carcinoma (LLC) cells derived from the lung of C57BL/6 mouse. Rat UCMSCs were then administered intratracheally five days later or intravenously on days 5 and 7. The tumor burdens were determined by measuring lung weight three weeks after the treatment.ResultsCo-culture of rat UCMSCs with LLC significantly attenuated the proliferation of LLC cells as monitored by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), a tetrazole cell proliferation assay, thymidine uptake, and direct cell counts. In vitro colony assays with rat UCMSCs as feeder layers markedly reduced LLC colony size and number. Co-culture of rat UCMSCs with LLCs causes G0/G1 arrest of cancer cells. This is evident in the decrease of cyclin A and CDK2 expression. The in vivo studies showed that rat UCMSC treatment significantly decreased tumor weight and the total tumor mass. Histological study revealed that intratracheally or systemically administered rat UCMSCs homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects.ConclusionsThese results indicate that rat UCMSCs alone remarkably attenuate the growth of lung carcinoma cells in vitro and in a mouse syngeneic lung carcinoma graft model and could be used for targeted cytotherapy for lung cancer.

Oncostatin M Modulates the Mesenchymal–Epithelial Transition of Lung Adenocarcinoma Cells by a Mesenchymal Stem Cell-Mediated Paracrine Effect

“…Stem cell-based therapy is an emerging strategy to treat various diseases, including cancer. Rat umbilical cord matrix stem cells have been shown to inhibit murine lung adenocarcinoma (LAC) growth (2). However, further work in human lung cancer models is still needed to clarify the therapeutic potential of this approach.…”

Wharton's Jelly Stem Cells as Agents for Cancer Therapy

“…The G0/G1 arrest is evident in the decrease of CDK2 expression [50]. In vivo studies showed that both human and rat UCMSC treatment significantly decreased tumor weights [32,33,49,50]. In particular, intratumoral or systemic administration of rat UCMSC caused complete regression of orthotopic Mat B III grafts in the female F344 rat mammary gland to undetectable levels by 34 to 38 days (Fig.…”

“…2). Histological studies revealed that intratracheally, intraperitoneally, or systemically administered rat UCMSC homed to tumor areas and survived for at least 3 weeks without any evidence of differentiation or adverse effects [33,50]. Therefore, the findings described above suggest that UCMSC may represent a new therapeutic modality and will have important implications for the treatment of patients with breast cancer, lung cancer, pancreatic cancer, and other types of cancer.…”

“…The secretory proteins/peptides are produced by either the UCMSC or the tumor cells in response to the UCMSC secretory products. Analysis with flow cytometry further revealed that co-culture with human UCMSC caused G2 arrest of MDA 231 human breast cancer cells [32], whereas rat UCMSC caused G0/G1 arrest of LLC [50] and murine pancreatic carcinoma cells [33]. The G0/G1 arrest is evident in the decrease of CDK2 expression [50].…”

“…Analysis with flow cytometry further revealed that co-culture with human UCMSC caused G2 arrest of MDA 231 human breast cancer cells [32], whereas rat UCMSC caused G0/G1 arrest of LLC [50] and murine pancreatic carcinoma cells [33]. The G0/G1 arrest is evident in the decrease of CDK2 expression [50]. In vivo studies showed that both human and rat UCMSC treatment significantly decreased tumor weights [32,33,49,50].…”