Chang Yuhan, Goldberg Victor M, Caplan Arnold I
Skeletal Research Center, Case Western Reserve University, Cleveland, OH 44106-7080, USA.
Clin Orthop Relat Res. 2006 Nov;452:242-9. doi: 10.1097/01.blo.0000229324.75911.c7.
We hypothesized that the high concentrations of gentamicin achieved after local administration would have toxic effects on human mesenchymal stem cells. These cells were isolated from bone marrow from three healthy adult donors and cultured with different concentrations of gentamicin (0 microg/mL, 50 microg/mL, 100 microg/mL, and 200 microg/mL) for 7 days. After 7 days of gentamicin exposure, we examined cell viability, proliferation, and in vitro and in vivo osteochondrogenic capacity. Gentamicin did not have an adverse effect on the viability of human mesenchymal stem cells in all test groups, but did inhibit cell proliferation at concentrations of 100 microg/mL and 200 microg/mL. In in vitro osteogenesis, gentamicin decreased the DNA content and alkaline phosphatase activity of human mesenchymal stem cells at an early stage (Days 4 and 8) in a dose-dependent manner. For chondrogenesis, glycosaminoglycan content and Type II and Type X collagen deposition were lower in the pellets made with cells expanded in gentamicin at 100 or 200 microg/mL relative to cells expanded in medium without gentamicin. A comparable effect on osteochondrogenesis was observed in an in vivo model. At a high concentration, gentamicin inhibits proliferation and differentiation of human bone marrow mesenchymal stem cells and could compromise the bone-healing process.
我们推测，局部给药后所达到的庆大霉素高浓度会对人间充质干细胞产生毒性作用。这些细胞从三名健康成年供体的骨髓中分离出来，并在不同浓度的庆大霉素（0微克/毫升、50微克/毫升、100微克/毫升和200微克/毫升）中培养7天。在庆大霉素暴露7天后，我们检测了细胞活力、增殖以及体外和体内的骨软骨生成能力。在所有测试组中，庆大霉素对人间充质干细胞的活力没有不良影响，但在100微克/毫升和200微克/毫升的浓度下确实抑制了细胞增殖。在体外成骨过程中，庆大霉素在早期（第4天和第8天）以剂量依赖的方式降低了人间充质干细胞的DNA含量和碱性磷酸酶活性。对于软骨生成，相对于在不含庆大霉素的培养基中扩增的细胞，在含有100或200微克/毫升庆大霉素的培养基中扩增的细胞所形成的小球中，糖胺聚糖含量以及II型和X型胶原蛋白沉积较低。在体内模型中观察到了对骨软骨生成的类似影响。在高浓度下，庆大霉素会抑制人骨髓间充质干细胞的增殖和分化，并可能损害骨愈合过程。
