State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University , Tianjin 300071, China.
Department of Endocrinology, The Second Affiliated Hospital, Kunming Medical University , Kunming 650101, Yunnan, China.
ACS Appl Mater Interfaces. 2018 Feb 7;10(5):4481-4493. doi: 10.1021/acsami.7b17533. Epub 2018 Jan 23.
Stem cell treatment for critical limb ischemia yields a limited therapeutic effect due to cell loss and dysfunction caused by local ischemic environment. Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell fate via mimicking the components of stem cell niche. Herein, we prepared a bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized with C domain peptide of insulin-like growth factor 1 (IGF-1C) and examined whether this hydrogel could augment stem cell survival and therapeutic potential. Our results showed that IGF-1C-modified hydrogel increased in vitro viability and proangiogenic activity of adipose-derived stromal cells (ADSCs). Moreover, cotransplantation of hydrogel and ADSCs into ischemic hind limbs of mice effectively ameliorated blood perfusion and muscle regeneration, leading to superior limb salvage. These therapeutic effects can be ascribed to improved ADSC retention, angiopoientin-1 secretion, and neovascularization, as well as reduced inflammatory cell infiltration. Additionally, hydrogel enhanced antifibrotic activity of ADSCs, as evidenced by decreased collagen accumulation at late stage. Together, our findings indicate that composite hydrogel modified by IGF-1C could promote survival and proangiogenic capacity of ADSCs and thereby represents a feasible option for cell-based treatment for critical limb ischemia.
由于局部缺血环境导致细胞丢失和功能障碍，干细胞治疗严重肢体缺血的疗效有限。仿生支架作为理想的细胞输送载体，通过模拟干细胞龛的成分来调节细胞命运。在此，我们通过混合壳聚糖和透明质酸制备了一种生物活性水凝胶，该水凝胶固定有胰岛素样生长因子 1（IGF-1）的 C 域肽，并研究了这种水凝胶是否可以增强干细胞的存活和治疗潜能。我们的结果表明，IGF-1 修饰的水凝胶增加了脂肪来源的基质细胞（ADSCs）的体外活力和促血管生成活性。此外，水凝胶和 ADSCs 共移植到小鼠缺血后肢中，可有效改善血液灌注和肌肉再生，从而实现更好的肢体保存。这些治疗效果可归因于 ADSC 的保留、血管生成素-1 分泌和新血管形成的改善，以及炎症细胞浸润的减少。此外，水凝胶增强了 ADSC 的抗纤维化活性，表现为晚期胶原积累减少。总之，我们的研究结果表明，IGF-1 修饰的复合水凝胶可以促进 ADSC 的存活和促血管生成能力，因此是严重肢体缺血细胞治疗的一种可行选择。
