Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment

Abstract

We here determine the influence of mesenchymal stem cell (MSC) therapy on the progression of solid tumors. The influence of MSCs was investigated in human colorectal cancer cells as well as in an immunocompetent rat model of colorectal carcinogenesis representative of the human pathology. Treatment with bone marrow (BM)‐derived MSCs significantly reduced both cancer initiation and cancer progression by increasing the number of tumor‐free animals as well as decreasing the number and the size of the tumors by half, thereby extending their lifespan. The attenuation of cancer progression was mediated by the capacity of the MSCs to modulate the immune component. Specifically, in the adenocarcinomas (ADKs) of MSC‐treated rats, the infiltration of CD68+ monocytes/macrophages was 50% less while the presence of CD3+ lymphocytes increased almost twofold. The MSCs reprogrammed the macrophages to become regulatory cells involved in phagocytosis thereby inhibiting the production of proinflammatory cytokines. Furthermore, the MSCs decreased NK (Natural Killer) and rTh17 cell activities, Treg recruitment, the presence of CD8+ lymphocytes and endothelial cells while restoring Th17 cell activity. The expression of miR‐150 and miR‐7 increased up to fivefold indicating a likely role for these miRNAs in the modulation of tumor growth. Importantly, MSC administration limited the damage of healthy tissues and attenuated tumor growth following radiotherapy. Taken together, we here show that that MSCs have durable action on colon cancer development by modulating the immune component of the tumor microenvironment. In addition, we identify two miRNAs associated with the capacity of MSCs to attenuate cancer growth. Stem Cells Translational Medicine 2019;8:285&300

Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes

“…Cells that are either slightly damaged or have been able to restore their lesions to a level of residual damage compatible with survival. These cells might turn out to be an effective source of cytokines (38), macromolecules (43), exosomes (44,45), reactive oxygen species (46), and reactive nitrogen species (18), and/or could suffer phenotypic changes to express hide-antigens in the tumors, which allow the triggering of the pro-immunogenic effects of radiotherapy on the tumors (19,20,47), with none of these possibilities being exclusive of the others, indeed all of them As we will explain below, this compartment may be enlarged by human-umbilical cord MSC transplantation (38,44,49).…”

“…In a recently published article, the influence of MSC cell therapy on the progress of solid tumors using an orthotopic cancer model of human colorectal cancer cells has been studied, as well as in an immunocompetent rat model of colorectal carcinogenesis representative of human pathology (49). In their results, the authors show that MSC administration to immunocompetent rats treated topically with methylnitronitrosoguanidine (MNNG), a strong carcinogen, reduced the growth of the tumors and improved overall survival.…”

“…The MSCs also protected healthy tissue from radiation damage by rising the levels of growth factors, reducing fibrosis, and facilitating intestinal recovery (49).…”

Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-β-Mediated JAK/STAT1 Pathway in vitro

“…International Publisher and tendon 6 . Therefore, MSCs that maintain their capacity for self-renewal ability contribute to a wide variety of endogenous organ and tissue repair 7 . In this rapidly expanding field, there is an increased focus on the relationship between stem and tumor cells.…”

“…ASCs are able to differentiate into specific cells when cultured in adipogenic or osteogenic medium 5,7 . In order to examine the potential of isolated ASCs for adipogenesis or osteogenesis, ASCs were cultured with adipogenic or osteogenic medium for 14 days, followed by an Oil-Red O or Alizarin Red S staining assay.…”