Article Abstract

Abnormally differentiated bone marrow mesenchymal stem cells develop into tumors in rats

Authors: Hongxia Yuan, Shiqi Liao, Jiayu Zeng, Xiaojuan Huang, Jieyu Zhang, Jing Zhao, Yuxian Wang, Hong Zhang, Xiaoqi Wang, Shidong Liao, Wenru Tang, Zhengli Wei, Caiping Tian, Rong Yang, Fang Liu, Hongyun Guo, Yongdong Zhang


Background: The generation of cancer stem cells is essential for the formation of tumor tissues; insightful understanding of the process may offer breakthroughs in tumor research and treatment. It is hypothesized that somatic stem cells (SSC) undergoing abnormal differentiation and evolution are able to form heterogeneous cell clusters, leading to onset of tumors.
Methods: Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured, then BMSCs were induced to differentiate into osteoblasts, adipocytes and neuroblasts. The differentiation process of BMSCs was interrupted at certain time points, and the cells at various stages of maturation were obtained. The resulting cells were further cultured to their fourth generation, then they were subject to the soft agar colony forming assay to screen the mutated cells that form clusters after losing their contact inhibition. The mutant cells were cultured for 5 days, then inoculated on the renal fascia of mice, which were pre-treated with immunosuppress reagent cyclophosphamide (CTX).
Results: Tissue biopsies confirmed a generation of heterogeneous cell clusters in the mice. These clusters morphologically resemble Hela cells, as they share similar pathophysiology, histomorphology and cell biology features with cancer tissues. These findings indicate that the evolved heterogeneous cell clusters can lead to cancer.
Conclusions: This study reveals the pathogenesis of tumors in respect to stem cells. Tumor stem cells may arise from the abnormal differentiation and evolution of SSC. From then on, tumor production evolves including heterogeneity, metastasis, immune escape and infinite increment.