Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model
Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model
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DOI：
10.1016/j.biomaterials.2015.12.032
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发表时间：
2016-03-01
期刊：
影响因子：
14
通讯作者：
Shoichet, M. S.
中科院分区：
文献类型：
--
作者：
Fuehrmann, T.;Tam, R. Y.;Shoichet, M. S.
多能干细胞及其分化后代的移植有可能保留或再生功能通路，改善中枢神经系统损伤后的功能。然而，由于存活率低和形成肿瘤的可能性，它们的实用性受到了阻碍。多肽修饰的生物材料在体外影响细胞的黏附、存活和分化，但其在体内的效果尚不确定。我们合成了一种由透明质酸和甲基纤维素组成的多肽修饰的微创可注射水凝胶，以增强人诱导的多能干细胞来源的少突胶质前体细胞的存活和分化。细胞在中度夹闭压迫大鼠脊髓损伤后进行亚急性移植。用RGD多肽和血小板衍生生长因子(PDGF-A)修饰的水凝胶促进了移植细胞的早期存活和整合。然而，当细胞被移植到存活时间较长的培养液中时，大量畸胎瘤的形成是明显的，这表明无论是这种细胞系还是它的培养方式都不适合人类使用。有趣的是，当细胞被移植到水凝胶中时，畸胎瘤的形成被减弱，那里的大多数细胞分化为神经胶质表型。因此，这种水凝胶促进了细胞的存活和整合，并通过促进细胞分化来减少畸胎瘤的形成。皇冠版权所有(C)2015由爱思唯尔有限公司出版。保留所有权利。
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.