A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation

被引:189
作者
Ballios, Brian G. [1 ]
Cooke, Michael J. [2 ]
Donaldson, Laura [3 ]
Coles, Brenda L. K. [4 ]
Morshead, Cindi M. [5 ,6 ]
van der Kooy, Derek [4 ,6 ]
Shoichet, Molly S. [2 ,6 ]
机构
[1] Univ Toronto, Fac Med, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada
[3] McMaster Univ, Div Ophthalmol, Dept Surg, Fac Hlth Sci, Hamilton, ON L8G 4X3, Canada
[4] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada
[5] Univ Toronto, Dept Surg, Toronto, ON M5S 1A8, Canada
[6] Univ Toronto, Donnelly Ctr, Toronto, ON M5S 3E1, Canada
关键词
INJURED SPINAL-CORD; PHOTORECEPTOR PRECURSORS; RETINAL REPAIR; MOUSE RETINA; RAT MODEL; DELIVERY; CD44; MICE; STROKE; DIFFERENTIATION;
D O I
10.1016/j.stemcr.2015.04.008
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The utility of stem cells and their progeny in adult transplantation models has been limited by poor survival and integration. We designed an injectable and bioresorbable hydrogel blend of hyaluronan and methylcellulose (HAMC) and tested it with two cell types in two animal models, thereby gaining an understanding of its general applicability for enhanced cell distribution, survival, integration, and functional repair relative to conventional cell delivery in saline. HAMC improves cell survival and integration of retinal stem cell (RSC)-derived rods in the retina. The pro-survival mechanism of HAMC is ascribed to the interaction of the CD44 receptor with HA. Transient disruption of the retinal outer limiting membrane, combined with HAMC delivery, results in significantly improved rod survival and visual function. HAMC also improves the distribution, viability, and functional repair of neural stem and progenitor cells (NSCs). The HAMC delivery system improves cell transplantation efficacy in two CNS models, suggesting broad applicability.
引用
收藏
页码:1031 / 1045
页数:15
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