Mesenchymal Stem Cells Treatment Aggravates Tumor Growth Regardless Its Route of Administration: An In vivo Study.

objectivesto clarify the effect of MSCs in cancer growth and to detect whether the rout of administration (either locally inside the tumor tissue or systemic )could affect the outcome of treatment or not.

methodsEighteen female mice were involved in the study. All mice were subcutaneously inoculated with Ehrlich tumor cells into the right flank. After three week of tumor growth; the mice were divided randomly in to three groups six mice for each ; group I: untreated Erlish tumor group; group II: Erlish tumor treated by local injection of 1 x106 MSCs/week inside the tumor tissue, group III: Erlish tumor treated by systemic injection of 1 x106 MSCs iv in tail vein/week. Tumor growth was recorded .After 4 weeks of stem cells injection, all rats were sacrificed by cervical dislocation and tumor tissues were collected for histopathological study. inflammatory cytokine TNF was assessed by ELISA, lncRNA MALAT ,NFKB and MMP2 genes expression were assessed by Quantitative RT-PCR.

resultsErlish tumor was developed as a well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The tumor growth regarding size and weight of tumor tissue was significantly aggravated after both local and systemic treatment MSCs (p value =0.007, 0.001) respectively. Inflammatory cytokines  TNF and NFKB were significantly elevated (p value <0.0001), lncRNA MALAT, MMP2 expressions were significantly induced (p value <0.0001), after MSCs treatment with more significant increase in those treated by local intratumor injection of MSCs compared to those treated by systemic MSCs(p value <0.0001).

conclusionEhrlich tumor model is feasible and easily monitored tumor model. Although MSCs have anti-inflammatory effect and the ability to regenerate the damaged tissue; it could aggravate tumor growth as it exploited by cancer cells for behave of tumor cells.