Cancer Microenvironment-Stimulated Mesenchymal Stem Cells in an Indirect Co-Culture System Influence Cancer Cell Growth and Apoptosis.

Abstract

Mesenchymal stem cells (MSCs) migrate to injured tissues, aiding tissue repair, remodeling, and wound healing. As tumors are often considered to have traits of "injured tissues," MSCs are recruited to tumor microenvironments where they can have pro- and antitumorigenic influences. This study assesses whether human mesenchymal stem cells (hMSCs) of shared ancestry exhibit similar tumorigenic properties. Bone marrow-derived (hBM-MSCs) and umbilical cord-derived (hUC-MSCs) MSCs embedded in collagen are cultured in conditioned media from lung adenocarcinoma (A549) cells to mimic the extracellular matrix and soluble cues of the cancer microenvironment. Cell viability, proliferation, and immunofluorescence analyses evaluate MSC behavior under these conditions. Further, A549 cells are exposed to conditioned media from cancer-stimulated MSCs to simulate indirect co-culture, and their response is assessed through viability, immunofluorescence, and flow cytometric analysis. Results show increased viability and proliferation of hBM-MSCs, morphological changes, and elevated alpha-smooth muscle actin expression, suggesting a transition toward cancer-associated fibroblasts. In contrast, hUC-MSCs display reduced viability and no morphological alterations. Conditioned media from cancer-exposed hUC-MSCs induce apoptosis in A549 cells, whereas hBM-MSCs support A549 growth. These findings demonstrate that, despite their common origin, hUC-MSCs and hBM-MSCs exhibit opposing responses to tumor cues and influence lung cancer cell behavior differently.