Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model

被引:155
作者
Fuehrmann, T. [1 ,2 ]
Tam, R. Y. [1 ,2 ]
Ballarin, B. [2 ]
Coles, B. [3 ,4 ]
Donaghue, I. Elliott [1 ,2 ]
van der Kooy, D. [3 ]
Nagy, A. [5 ]
Tator, C. H. [6 ,7 ]
Morshead, C. M. [2 ,8 ]
Shoichet, M. S. [1 ,2 ]
机构
[1] Univ Toronto, Dept Chem Engn & Appl Chem, 200 Coll St, Toronto, ON M5S 3E5, Canada
[2] Inst Biomat & Biomed Engn, 160 Coll St,Room 530, Toronto, ON M5S 3E1, Canada
[3] Univ Toronto, Dept Mol Genet, 1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada
[4] Univ Toronto, Donnelly Ctr, 160 Coll St, Toronto, ON M5S 3E1, Canada
[5] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada
[6] Univ Toronto, Toronto Western Res Inst, Krembil Neurosci Ctr, 399 Bathurst St, Toronto, ON M5T 2S8, Canada
[7] Univ Toronto, Dept Surg, 399 Bathurst St, Toronto, ON M5T 2S8, Canada
[8] Univ Toronto, Donnelly Ctr, Dept Surg, 160 Coll St, Toronto, ON M5S 3E1, Canada
基金
加拿大健康研究院;
关键词
Cell adhesion molecules; Hydrogel; Differentiation; Induced pluripotent stem cells; Oligodendrocytes; Spinal cord injury; Cell transplantation; FUNCTIONAL RECOVERY; PROGENITOR CELLS; DELIVERY-SYSTEM; GROWTH; TRANSPLANTATION; DIFFERENTIATION; MOLECULES; REPAIR; REMYELINATION; PRECURSORS;
D O I
10.1016/j.biomaterials.2015.12.032
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Transplantation of pluripotent stem cells and their differentiated progeny has the potential to preserve or regenerate functional pathways and improve function after central nervous system injury. However, their utility has been hampered by poor survival and the potential to form tumors. Peptide-modified biomaterials influence cell adhesion, survival and differentiation in vitro, but their effectiveness in vivo remains uncertain. We synthesized a peptide-modified, minimally invasive, injectable hydrogel comprised of hyaluronan and methylcellulose to enhance the survival and differentiation of human induced pluripotent stem cell-derived oligodendrocyte progenitor cells. Cells were transplanted sub acutely after a moderate clip compression rat spinal cord injury. The hydrogel, modified with the RGD peptide and platelet-derived growth factor (PDGF-A), promoted early survival and integration of grafted cells. However, prolific teratoma formation was evident when cells were transplanted in media at longer survival times, indicating that either this cell line or the way in which it was cultured is unsuitable for human use. Interestingly, teratoma formation was attenuated when cells were transplanted in the hydrogel, where most cells differentiated to a glial phenotype. Thus, this hydrogel promoted cell survival and integration, and attenuated teratoma formation by promoting cell differentiation. Crown Copyright (C) 2015 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:23 / 36
页数:14
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