IGF-1 C Domain-Modified Hydrogel Enhances Cell Therapy for AKI

被引:114
作者
Feng, Guowei [1 ,2 ,3 ]
Zhang, Jimin [2 ]
Li, Yang [1 ]
Nie, Yan [1 ]
Zhu, Dashuai [1 ]
Wang, Ran [1 ]
Liu, Jianfeng [4 ,5 ]
Gao, Jie [2 ]
Liu, Na [2 ]
He, Ningning [1 ]
Du, Wei [1 ]
Tao, Hongyan [1 ]
Che, Yongzhe [1 ]
Xu, Yong [3 ]
Kong, Deling [2 ]
Zhao, Qiang [2 ]
Li, Zongjin [1 ,2 ]
机构
[1] Nankai Univ, Coll Life Sci, Minist Educ, Sch Med, Tianjin, Peoples R China
[2] Nankai Univ, Coll Life Sci, Minist Educ, State Key Lab Med Chem Biol,Key Lab Bioact Mat, Tianjin, Peoples R China
[3] Tianjin Med Univ, Tianjin Inst Urol, Dept Urol, Hosp 2, 22 Pingjiang Rd, Tianjin 300211, Peoples R China
[4] Chinese Acad Med Sci, Inst Radiat Med, Tianjin Key Lab Mol Nucl Med, Tianjin, Peoples R China
[5] Peking Union Med Coll, Tianjin, Peoples R China
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2016年 / 27卷 / 08期
基金
中国国家自然科学基金;
关键词
MESENCHYMAL STEM-CELLS; GROWTH-FACTOR-I; NITRIC-OXIDE; EXTRACELLULAR-MATRIX; REPAIR; PROMOTION; PEPTIDE; FIBROSIS; SURVIVAL; DELIVERY;
D O I
10.1681/ASN.2015050578
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
100201 [内科学]; 100221 [泌尿外科学];
摘要
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.
引用
收藏
页码:2357 / 2369
页数:13
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