Feng Guowei, Zhang Jimin, Li Yang, Nie Yan, Zhu Dashuai, Wang Ran, Liu Jianfeng, Gao Jie, Liu Na, He Ningning, Du Wei, Tao Hongyan, Che Yongzhe, Xu Yong, Kong Deling, Zhao Qiang, Li Zongjin
School of Medicine and State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China; Department of Urology, Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, China; and.
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China;
J Am Soc Nephrol. 2016 Aug;27(8):2357-69. doi: 10.1681/ASN.2015050578. Epub 2016 Feb 11.
Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan-IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan-IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI.
移植后细胞保留率低和植入率低限制了干细胞疗法在急性肾损伤（AKI）治疗中的成功应用。由水凝胶基质和生长因子组成的工程化微环境通过模拟天然干细胞生态位成分，在控制干细胞命运方面越来越成功。在此，我们通过将胰岛素样生长因子-1（IGF-1）的C结构域肽（IGF-1C）固定在壳聚糖上合成了一种生物活性水凝胶，我们假设这种水凝胶可以为脂肪来源的间充质干细胞（ADSCs）提供有利的生态位，从而提高急性肾损伤模型中的细胞存活率。体外研究表明，与无凝胶或仅壳聚糖水凝胶相比，壳聚糖-IGF-1C水凝胶通过旁分泌作用提高了细胞活力。在体内，壳聚糖-IGF-1C水凝胶与ADSCs共同移植到缺血性肾脏中改善了肾功能，这可能是通过观察到的促进干细胞存活和血管生成实现的，这在生物发光成像和纤维化减轻中得到了体现。总之，固定在壳聚糖水凝胶上的IGF-1C为ADSCs提供了一个人工微环境，可能是一种有前途的急性肾损伤治疗方法。
