BMP-6 Facilitates the Transdifferentiation of BMSCs into Salivary Acinar Cells

Objective:  The purposre of this study was to explore the crucial induction factors for transdifferentiation of bone marrow stem cells into salivary acinar cells to develop a feasible and elegant therapy for functional restoration and tissue regeneration of salivary gland. Method:  Bone marrow stem cells and submandibular gland acinar cells were obtained respectively from 4-week-old C57BL/6 mice. We utilized a double-chamber system for indirect co-culture of these two kinds of cells. Bone marrow stem cells were seeded at lower wells, while acinar cells were seeded at upper inserts with a 0.4μm permeable membrane that facilitate media and signal molecules flow through. Microarray analysis was preformed to examine the genomic changes of bone marrow stem cells after co-cultured with acinar cells for 5 days and 10 days respectively. Furthermore, potential induction factors were added additionally to compare the transdifferentiation results by using the amylase activity assay, and were confirmed by immunofluorescence staining observed under florescent microscopy to identify the phenotype of the transdifferentiated cells. Result: After co-cultured for 5 days and 10 days, bone marrow stem cells were transdifferentiated into acinar-like cells with expression of α-amylase and functional activities for starch digestion. The results of microarray analysis demonstrated that bone morphogenetic protein (BMP)-6 was one of the top-ranked genes which were up-regulated after co-culture. By adding BMP-6 in the co-culture system, the number of transdifferentiated acinar-like cells was increased. We also found that BMP-6 could promote the transdifferentiation of bone marrow stem cells into acinar-like cells even without co-culturing with acinar cells. Conclusion:  In this study, we demonstrated that BMP-6 is an important induction factor for promoting the transdifferentiation of bone marrow stem cells into salivary acinar cells. It is worthy for further study of the detailed mechanism and signal pathways involved and further clinical application of cell theray for salivary gland regeneration.