Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles.
Creating a stem cell niche in the inner ear using self-assembling peptide amphiphiles.
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DOI：
10.1371/journal.pone.0190150
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kessler JA
中科院分区：
文献类型：
--
作者：
Matsuoka AJ;Sayed ZA;Stephanopoulos N;Berns EJ;Wadhwani AR;Morrissey ZD;Chadly DM;Kobayashi S;Edelbrock AN;Mashimo T;Miller CA;McGuire TL;Stupp SI;Kessler JA
人类胚胎干细胞（hESCs）用于螺旋神经节再生将需要促进耳神经祖细胞（ONP）分化的技术，将细胞锚定到解剖学上合适的和特定的龛位，以及移植后细胞的长期存活。在这项研究中，我们使用显示IKVAV表位的自组装肽两亲性（PA）分子（IKVAV-PA）为hesc来源的ONPs创造了一个生态位，这些ONPs在移植到啮齿动物内耳后支持神经元在体外和体内的分化和存活。IKVAV-PA凝胶的一个特点是它能够形成有组织的纳米纤维，促进定向神经突生长。在IKVAV-PA凝胶中培养hesc来源的ONPs不改变细胞增殖或活力。然而，IKVAV-PA凝胶的存在增加了表达神经元标志物β - iii微管蛋白的细胞数量，并改善了神经突的延伸。IKVAV-PA凝胶的自组装特性使其能够作为液体注入内耳，在体内凝胶化后为移植细胞创造一个生物物理生态位。与对照组相比，将ONPs联合IKVAV-PA注射到X-SCID大鼠的modiolus中，可增加注射部位周围细胞的存活率和定位。人尸体颞骨研究证明了经乳突手术入路用于临床耳蜗内注射IKVAV-PA/ONP组合的技术可行性。将干细胞移植与注射自组装PA凝胶相结合，创造支持生态位可能会改善螺旋神经节再生的临床方法。
The use of human embryonic stem cells (hESCs) for regeneration of the spiral ganglion will require techniques for promoting otic neuronal progenitor (ONP) differentiation, anchoring of cells to anatomically appropriate and specific niches, and long-term cell survival after transplantation. In this study, we used self-assembling peptide amphiphile (PA) molecules that display an IKVAV epitope (IKVAV-PA) to create a niche for hESC-derived ONPs that supported neuronal differentiation and survival both in vitro and in vivo after transplantation into rodent inner ears. A feature of the IKVAV-PA gel is its ability to form organized nanofibers that promote directed neurite growth. Culture of hESC-derived ONPs in IKVAV-PA gels did not alter cell proliferation or viability. However, the presence of IKVAV-PA gels increased the number of cells expressing the neuronal marker beta-III tubulin and improved neurite extension. The self-assembly properties of the IKVAV-PA gel allowed it to be injected as a liquid into the inner ear to create a biophysical niche for transplanted cells after gelation in vivo. Injection of ONPs combined with IKVAV-PA into the modiolus of X-SCID rats increased survival and localization of the cells around the injection site compared to controls. Human cadaveric temporal bone studies demonstrated the technical feasibility of a transmastoid surgical approach for clinical intracochlear injection of the IKVAV-PA/ONP combination. Combining stem cell transplantation with injection of self-assembling PA gels to create a supportive niche may improve clinical approaches to spiral ganglion regeneration.
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影响因子：
64.8
作者：
Chen, Wei;Jongkamonwiwat, Nopporn;Abbas, Leila;Eshtan, Sarah Jacob;Johnson, Stuart L.;Kuhn, Stephanie;Milo, Marta;Thurlow, Johanna K.;Andrews, Peter W.;Marcotti, Walter;Moore, Harry D.;Rivolta, Marcelo N.
通讯作者：
Rivolta, Marcelo N.
影响因子：
46.9
作者：
Hockemeyer, Dirk;Soldner, Frank;Beard, Caroline;Gao, Qing;Mitalipova, Maisam;DeKelver, Russell C.;Katibah, George E.;Amora, Ranier;Boydston, Elizabeth A.;Zeitler, Bryan;Meng, Xiangdong;Miller, Jeffrey C.;Zhang, Lei;Rebar, Edward J.;Gregory, Philip D.;Urnov, Fyodor D.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
影响因子：
9.7
作者：
Berns EJ;Álvarez Z;Goldberger JE;Boekhoven J;Kessler JA;Kuhn HG;Stupp SI
通讯作者：
Stupp SI
DOI：
10.1002/neu.20310
发表时间：
2006-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Corrales, C. Eduardo;Pan, Luying;Edge, Albert S. B.
通讯作者：
Edge, Albert S. B.
影响因子：
5.2
作者：
Henderson, JK;Draper, JS;Andrews, PW
通讯作者：
Andrews, PW