Cellular Stiffness as a Novel Sternness Marker in the Corneal Limbus
Cellular Stiffness as a Novel Sternness Marker in the Corneal Limbus
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DOI：
10.1016/j.bpj.2016.09.005
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发表时间：
2016-10-18
影响因子：
3.4
通讯作者：
Sulchek, Todd
中科院分区：
文献类型：
--
作者：
Bongiorno, Tom;Chojnowski, Jena L.;Sulchek, Todd
健康的眼睛包含一群不断更新角膜上皮的角膜缘干细胞(LSCs)。然而，每年有100万美国人因角膜损伤或疾病，包括LSC缺乏症(LSCD)而受到视力严重下降的困扰。角膜移植技术的最新进展有望通过植入健康的LSCs来修复角膜，以促进再生；然而，成功仅限于含有足够高比例LSCs的移植组织。使用分子严谨标记筛选角膜缘组织以寻找合适的植入物的尝试因对LSC表型的签名知之甚少而感到困惑。对于来自角膜缘的细胞，我们表明细胞硬度作为干细胞指标的性能与Delta NP63α的性能相当，Delta NP63α是一种常见的分子标记。结合最新的基于生物物理的细胞分选方法，本文提出的生物力学硬度标记物可能使从异种角膜细胞群中快速纯化LSC成为可能，从而潜在地使临床医生和研究人员能够产生具有足够高比例LSC的角膜移植，而不考虑供体组织中LSC的百分比。
Healthy eyes contain a population of limbal stem cells (LSCs) that continuously renew the corneal epithelium. However, each year, 1 million Americans are afflicted with severely reduced visual acuity caused by corneal damage or disease, including LSC deficiency (LSCD). Recent advances in corneal transplant technology promise to repair the cornea by implanting healthy LSCs to encourage regeneration; however, success is limited to transplanted tissues that contain a sufficiently high percentage of LSCs. Attempts to screen limbal tissues for suitable implants using molecular sternness markers are confounded by the poorly understood signature of the LSC phenotype. For cells derived from the corneal limbus, we show that the performance of cell stiffness as a stemness indicator is on par with the performance of Delta NP63 alpha, a common molecular marker. In combination with recent methods for sorting cells on a biophysical basis, the biomechanical sternness markers presented here may enable the rapid purification of LSCs from a heterogeneous population of corneal cells, thus potentially enabling clinicians and researchers to generate corneal transplants with sufficiently high fractions of LSCs, regardless of the LSC percentage in the donor tissue.