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人胚胎干细胞在豚鼠听觉上皮中的植入存活。

Survival of human embryonic stem cells implanted in the guinea pig auditory epithelium.

机构信息

Kresge Hearing Research Institute, Otolaryngology - Head and Neck Surgery, The University of Michigan Medical School, MSRB-3, Rm. 9301 1150 W. Medical Center Dr. Ann Arbor, MI 48109-5648, USA.

Department of Otorhinolaryngology and Head &Neck Surgery, Dankook University Hospital, 119, Dandae-ro, Dongnam-gu, Cheonan-si, Chungnam, 31116, Korea.

出版信息

Sci Rep. 2017 Apr 7;7:46058. doi: 10.1038/srep46058.

DOI:10.1038/srep46058
PMID:28387239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5384248/
Abstract

Hair cells in the mature cochlea cannot spontaneously regenerate. One potential approach for restoring hair cells is stem cell therapy. However, when cells are transplanted into scala media (SM) of the cochlea, they promptly die due to the high potassium concentration. We previously described a method for conditioning the SM to make it more hospitable to implanted cells and showed that HeLa cells could survive for up to a week using this method. Here, we evaluated the survival of human embryonic stem cells (hESC) constitutively expressing GFP (H9 Cre-LoxP) in deaf guinea pig cochleae that were pre-conditioned to reduce potassium levels. GFP-positive cells could be detected in the cochlea for at least 7 days after the injection. The cells appeared spherical or irregularly shaped, and some were aggregated. Flushing SM with sodium caprate prior to transplantation resulted in a lower proportion of stem cells expressing the pluripotency marker Oct3/4 and increased cell survival. The data demonstrate that conditioning procedures aimed at transiently reducing the concentration of potassium in the SM facilitate survival of hESCs for at least one week. During this time window, additional procedures can be applied to initiate the differentiation of the implanted hESCs into new hair cells.

摘要

成熟耳蜗中的毛细胞不能自发再生。一种恢复毛细胞的潜在方法是干细胞疗法。然而，当细胞被移植到耳蜗的中阶（SM）时，由于高钾浓度，它们会迅速死亡。我们之前描述了一种调节 SM 的方法，使其更适合植入的细胞，并表明使用这种方法，HeLa 细胞可以存活长达一周。在这里，我们评估了在预先调节以降低钾水平的聋豚鼠耳蜗中持续表达 GFP（H9 Cre-LoxP）的人胚胎干细胞（hESC）的存活情况。在注射后至少 7 天可以在耳蜗中检测到 GFP 阳性细胞。这些细胞呈球形或不规则形状，有些聚集在一起。在移植前用辛酸钠冲洗 SM 可导致表达多能性标志物 Oct3/4 的干细胞比例降低，同时增加细胞存活率。这些数据表明，旨在暂时降低 SM 中钾浓度的调节程序可促进 hESC 至少存活一周。在此时间窗口内，可以应用其他程序来启动植入的 hESC 分化为新的毛细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabc/5384248/eb648f662307/srep46058-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabc/5384248/eb648f662307/srep46058-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabc/5384248/9d418129dad6/srep46058-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dabc/5384248/9c80df0d29ad/srep46058-f2.jpg
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