Dalonneau Fabien, Liu Xi Qiu, Sadir Rabia, Almodovar Jorge, Mertani Hichem C, Bruckert Franz, Albiges-Rizo Corinne, Weidenhaupt Marianne, Lortat-Jacob Hugues, Picart Catherine
CNRS UMR 5628 (LMGP), 3 parvis Louis Néel, 38016 Grenoble, France.
Université Grenoble Alpes, LMGP, 3 parvis Louis Néel, 38016 Grenoble, France.
Biomaterials. 2014 May;35(15):4525-4535. doi: 10.1016/j.biomaterials.2014.02.008. Epub 2014 Mar 5.
Several chemokines are important in muscle myogenesis and in the recruitment of muscle precursors during muscle regeneration. Among these, the SDF-1α chemokine (CXCL12) is a potent chemoattractant known to be involved in muscle repair. SDF-1α was loaded in polyelectrolyte multilayer films made of poly(L-lysine) and hyaluronan to be delivered locally to myoblast cells in a matrix-bound manner. The adsorbed amounts of SDF-1α were tuned over a large range from 100 ng/cm(2) to 5 μg/cm(2), depending on the initial concentration of SDF-1α in solution, its pH, and on the film crosslinking extent. Matrix-bound SDF-1α induced a striking increase in myoblast spreading, which was revealed when it was delivered from weakly crosslinked films. It also significantly enhanced cell migration in a dose-dependent manner, which again depended on its presentation by the biopolymeric film. The low-crosslinked film was the most efficient in boosting cell migration. Furthermore, matrix-bound SDF-1α also increased the expression of myogenic markers but the fusion index decreased in a dose-dependent manner with the adsorbed amount of SDF-1α. At high adsorbed amounts of SDF-1α, a large number of Troponin T-positive cells had only one nucleus. Overall, this work reveals the importance of the presentation mode of SDF-1α to emphasize its effect on myogenic processes. These films may be further used to provide insight into the role of SDF-1α presented by a biomaterial in physiological or pathological processes.
几种趋化因子在肌肉生成以及肌肉再生过程中肌肉前体细胞的募集方面起着重要作用。其中，SDF-1α趋化因子（CXCL12）是一种已知参与肌肉修复的强效化学引诱剂。SDF-1α被负载于由聚（L-赖氨酸）和透明质酸制成的聚电解质多层膜中，以便以基质结合的方式局部递送至成肌细胞。根据溶液中SDF-1α的初始浓度、其pH值以及膜的交联程度，SDF-1α的吸附量可在100 ng/cm²至5 μg/cm²的较大范围内进行调节。基质结合的SDF-1α可显著增加成肌细胞的铺展，当它从弱交联膜中递送时这一现象得以显现。它还以剂量依赖的方式显著增强细胞迁移，这同样取决于生物聚合物膜对其的呈现方式。低交联膜在促进细胞迁移方面最为有效。此外，基质结合的SDF-1α还增加了肌源性标志物的表达，但融合指数随SDF-1α的吸附量呈剂量依赖性降低。在高吸附量的SDF-1α情况下，大量肌钙蛋白T阳性细胞只有一个细胞核。总体而言，这项工作揭示了SDF-1α呈现方式对强调其对肌源性过程影响的重要性。这些膜可进一步用于深入了解生物材料呈现的SDF-1α在生理或病理过程中的作用。
