Institute of Biomedical Sciences, Academia Sinica , No. 128 Sec. 2, Academia Road, Taipei 115, Taiwan.
Biomacromolecules. 2014 Feb 10;15(2):564-73. doi: 10.1021/bm401583b. Epub 2014 Jan 6.
The use of biomaterial carriers to improve the therapeutic efficacy of stem cells is known to augment cell delivery, retention, and viability. However, the way that carrier clearance kinetics boosts stem cell delivery and impacts stem cell function remains poorly characterized. In this study, we designed a platform to simultaneously quantify carrier clearance and stem cell retention to evaluate the impact of carrier clearance kinetics on stem cell retention. Additionally, a murine model of hindlimb ischemia was employed to investigate the effects of various cell retention profiles on mitigating peripheral arterial disease. To image the in vivo behaviors of material and cells, we used biotinylated hyaluronan with fluorescently labeled streptavidin and Discosoma sp. Red (Ds-Red)-expressing human mesenchymal stem cells. We found that the retention of transplanted stem cells was closely related to the remaining biomaterial. Furthermore, therapeutic effectiveness was also affected by stem cell retention. These results demonstrate that low-molecular-weight hyaluronan had a slow clearance and high cell retention profile, improving the therapeutic efficacy of human stem cells.
利用生物材料载体来提高干细胞的治疗效果已被证实可以增加细胞的递送、保留和活力。然而，载体清除动力学如何促进干细胞的递送以及影响干细胞功能仍未得到很好的描述。在本研究中，我们设计了一个平台来同时定量载体清除和干细胞保留，以评估载体清除动力学对干细胞保留的影响。此外，我们还利用后肢缺血的小鼠模型来研究不同的细胞保留曲线对减轻外周动脉疾病的影响。为了在体内可视化材料和细胞的行为，我们使用了带有荧光标记链霉亲和素的生物素化透明质酸和表达 Discosoma sp. Red (Ds-Red) 的人骨髓间充质干细胞。我们发现，移植干细胞的保留与剩余的生物材料密切相关。此外，治疗效果也受到干细胞保留的影响。这些结果表明，低分子量透明质酸具有缓慢的清除和高细胞保留特性，从而提高了人源干细胞的治疗效果。
