Mesenchymal stem cells (MSC) are heterogeneous cells of complex nature that show different potentials while different culture conditions can modify their functionalities through interactions with the microenviroment. Here, we found that bone marrow (BM) MSC from different donor sources and passages that expressed higher levels of α6 integrin subunit (ITGA6), showed higher clonogenicity, migration and differentiation potential. ITGA6 showed important roles improving these potentials and regulating proliferation through protein kinase B (AKT) pathway and cell cycle inhibitor proteins p53 and p21. Moreover, ITGA6 downregulation impaired migration. Cell confluence regulated ITGA6, increasing its expression in low density cultures and decreasing in high density cultures. Besides, ITGA6- cells expressed ITGA6 when seeded at low densities. We found higher ITGA6 expression on fibronectin substrates at lower confluency. Fibronectin increased proliferation, clonogenicity, activation of AKT, decreased cell cycle inhibitor proteins and augmented growth factors expression. Spheres-derived MSC showed higher ITGA6 expression and enhanced potentials for migration, clonogenicity and proliferation. In conclusion, though there is an intrinsic regulation of ITGA6 expression, associated to the progenitor potential of BM-MSC, this expression is regulated by culture conditions and is translated in changes in cell behavior and proliferation. This knowledge could be used to enhance the potential of BM-MSC for clinical application.

间充质干细胞（MSC）是性质复杂的异质细胞，表现出不同的潜力，而不同的培养条件可以通过与微环境的相互作用来改变其功能。在这里，我们发现来自不同供体来源和传代的骨髓（BM）MSC表达更高水平的α6整合素亚基（ITGA6），表现出更高的克隆形成、迁移和分化潜力。 ITGA6 通过蛋白激酶 B (AKT) 途径和细胞周期抑制剂蛋白 p53 和 p21 表现出改善这些潜力并调节增殖的重要作用。此外，ITGA6 下调会损害迁移。细胞汇合调节 ITGA6，在低密度培养物中增加其表达，在高密度培养物中减少表达。此外，ITGA6-细胞在低密度接种时表达ITGA6。我们发现在较低的汇合度下，纤连蛋白底物上的 ITGA6 表达较高。纤连蛋白增加增殖、克隆形成、AKT 激活、减少细胞周期抑制剂蛋白并增强生长因子表达。球体来源的 MSC 显示出更高的 ITGA6 表达，并增强了迁移、克隆形成和增殖的潜力。总之，虽然 ITGA6 表达存在内在调节，与 BM-MSC 的祖细胞潜力相关，但这种表达受培养条件调节，并转化为细胞行为和增殖的变化。这些知识可用于增强 BM-MSC 的临床应用潜力。