Abstract:

BACKGROUND: Tumor has been considered as a specific nonhealing trauma. Bone marrow mesenchymal stem cells participate in tumor mesenchymal reconstitution by tumor tissue homing and differentiation into mesenchyme, resulting in changing tumor microenvironment and affecting tumor growth and transfer.
OBJECTIVE: To explore the mechanisms of participation of bone marrow mesenchymal stem cells in tumor tissue repair in an A549 lung cancer-bearing mouse model.
METHODS: Bone marrow mesenchymal stem cells were isolated in vitro, cultured, and identified using flow cytometry, and then used to establish a mouse model of A549 lung cancer-bearing. In the experimental group, human bone marrow mesenchymal stem cells were injected into tissue surrounding the tumor. In the control group, an equal volume of PBS was injected. Animal survival condition and tumor size were compared. At 4 weeks, the specimens were harvested. Hematoxylin-eosin staining was used to compare tumor tissue. Masson staining was utilized to compare collagen fiber content. Reverse transcription-PCR was employed to detect the expression of α-smooth muscle actin. Immunohistochemistry was used to examine the expression of fibroblast specific protein and fibroblast activation protein to reflect the degree of interstitial fibers in tumor tissue in both groups. The expression levels of vascular endothelial growth factor, hepatocyte growth factor, interleukin-6 and tenescin-C were compared between the two groups using immunohistochemistry.
RESULTS AND CONCLUSION: Bone marrow mesenchymal stem cells promoted tumor growth in tumor-bearing mice. The growth rate of tumor tissue in experimental group was faster than the control group (P < 0.05). Compared with the control group, α-smooth muscle actin mRNA expression was significantly higher in the experimental group. Immunohistochemistry was used to detect the expression of tumor angiogenesis factors markers (fibroblast specific protein and fibroblast activation protein) in tumor tissue of experimental group. The expression levels of vascular endothelial growth factor, hepatocyte growth factor, interleukin-6 and tenescin-C were significantly greater in the experimental group than in the control group (P < 0.05). Results indicated that bone marrow mesenchymal stem cells differentiated into fibroblasts in tumor microenvironment, participated in the formation and construction of tumor stroma as well as promoted the growth and repair of tumor via the secretion of vascular endothelial growth factor, hepatocyte growth factor, interleukin-6 and tenescin-C.

Key words: stem cells, bone marrow-derived stem cells, bone marrow mesenchymal stem cells, A549 tumor-bearing mice, tumor-associated fibroblasts, stroma fiber, immunohistochemistry, α-smooth muscle actin, vascular endothelial growth factor, hepatocyte growth factor, interleukin-6, tenescin-C, stem cell photographs-containing paper