Quiescent innate and adaptive immune responses maintain the long-term integrity of corneal endothelium reconstituted through allogeneic cell injection therapy.

Quiescent innate and adaptive immune responses maintain the long-term integrity of corneal endothelium reconstituted through allogeneic cell injection therapy.
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DOI:
10.1038/s41598-022-22522-4
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发表时间:
2022-10-27
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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本研究旨在阐明应用于细胞注射治疗的培养人角膜内皮细胞(hCEC)的获得性和先天性免疫应答的免疫原性,细胞注射治疗是一种新建立的角膜内皮衰竭模式。对34例角膜内皮功能衰竭患者进行了前房注射hCEC悬液治疗。术后随访5-8年,无免疫排斥反应发生。2例穿透性角膜移植术后内皮衰竭患者和1例后弹力层剥脱自动内皮角膜移植术失败患者的细胞注射治疗成功。ELISPOT分析在同种异体混合淋巴细胞反应中进行,以同种异体抗原与注射的hCEC上的同种异体抗原相同,在接受hCEC注射的患者的外周血单核细胞中引起稀疏的IFN-γ特异性斑点。该疗法产生了简单而光滑的移植物-宿主连接,没有伤口应力。将C57 BL/6 CEC注射到6周前排斥C57 BL/6角膜的BALB/c小鼠的前房中,在同种异体抗原的第二次攻击后没有诱导炎症反应的迹象。总的来说,在房水中注射hCEC细胞悬浮液诱导免疫耐受,这有助于重建内皮的存活。
This study aims to clarify the immunogenicity in acquired and innate immune responses of cultured human corneal endothelial cells (hCECs) applied for cell injection therapy, a newly established modality for corneal endothelium failures. Thirty-four patients with corneal endothelial failure received injection of allogeneic hCEC suspension into anterior chamber. No sign of immunological rejection was observed in all 34 patients during the 5–8 years postoperative follow-up period. Cell injection therapy was successful in 2 patients treated for endothelial failure after penetrating keratoplasty and one patient with Descemet membrane stripping automated endothelial keratoplasty failure. ELISPOT assays performed in allo-mixed lymphocyte reaction to the alloantigen identical to that on the injected hCECs, elicited sparse IFN-γ-specific spots in the peripheral blood mononuclear cells of patients who received hCEC injection. The therapy generated simple and smooth graft-host junctions without wound stress. The injection of C57BL/6 CECs into the anterior chamber of BALB/c mice, which rejected C57BL/6 corneas 6 weeks ago, induced no sign of inflammatory reactions after the second challenge of alloantigen. Collectively, injection of the hCEC cell suspension in the aqueous humor induces immune tolerance that contributes to the survival of the reconstituted endothelium.
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