Conclusion
These findings suggest a strong supporting affinity between MSCs and AML cells within the leukemic niche, where TGF-β1 and CXCL12 pathways play an important role.
Discussion
Human MSCs are potent feeder cells, able to maintain AML cells in long-term culture. This favorable co-existence seems to be due in part to molecules important for communication within the niche. Blockade of TGF-β1 and CXCL12 was associated with different effects on AML cell proliferation and chemotherapy resistance. Conclusion: These findings suggest a strong supporting affinity between MSCs and AML cells within the leukemic niche, where TGF-β1 and CXCL12 pathways play an important role.
Methods
Human MSCs were obtained by BM aspirates and their phenotype and functional properties were confirmed in vitro. Co-cultures of AML cells on MSCs were initiated and compared to those on mouse fibroblasts (MS-5) and liquid cultures. Additionally, the effect of blocking CXCR4 and TGF-β1 on AML cells was tested with and without the addition of cytarabine.
Results
MSCs from BM showed a typical phenotype and differentiation pattern. Co-culture of AML cells on MSCs resulted in a significantly higher proliferation capacity than on MS-5 or liquid culture. Blockade of TGF-β1 increased AML cell proliferation and chemosensibility, while the CXCR4 antagonist plerixafor showed anti-proliferative effects and did not change cytarabine-induced cell death compared to control.