Repeated intravenous transplantation of human umbilical cord mesenchymal stem cells does not promote tumorigenesis in EGFR-mutated lung cancer mice

Mesenchymal stem cells (MSCs) are extensively studied in clinical trials for their potential therapeutic applications in degenerative and inflammatory diseases and disorders. Despite the lack of clinical evidence indicating that MSCs induce carcinogenesis, the immunosuppressive and proangiogenic functions of MSCs are considered as potential risks involving immune escape and tumor occurrence in programming tumor microenvironment. Previously, many groups had studied the tumorigenic safety of MSCs, but most of these studies were modeled in immuno-deficient mice with different types and sources of transplanted tumors, leaving varied and controversial conclusions. In this study, we developed a new xenograft model by repeatedly transplanting human umbilical cord mesenchymal stem cells (UC-MSCs) into transgenic mice via tail vein. These mice, carried a human-derived mutated EGFR with a normal immune system, were used to investigate whether UC-MSCs promote the occurrence of lung adenocarcinoma. The duration, dynamics, and pathological characteristics of the early stages of the disease were analyzed. In general, repeated transplantation of UC-MSCs neither accelerated the occurrence of lung cancer and the progression of bronchial alveolar carcinoma nor promoted a pro-tumor immune microenvironment. These results suggest that repeated transplantation of UC-MSCs does not increase the risk of lung cancer.