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脂肪来源的干细胞与治疗青光眼的潜力整合到小梁网中。

Adipose-derived stem cells integrate into trabecular meshwork with glaucoma treatment potential.

机构信息

Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.

出版信息

FASEB J. 2020 May;34(5):7160-7177. doi: 10.1096/fj.201902326R. Epub 2020 Apr 7.

Abstract

The trabecular meshwork (TM) is an ocular tissue that maintains intraocular pressure (IOP) within a physiologic range. Glaucoma patients have reduced TM cellularity and, frequently, elevated IOP. To establish a stem cell-based approach to restoring TM function and normalizing IOP, human adipose-derived stem cells (ADSCs) were induced to differentiate to TM cells in vitro. These ADSC-TM cells displayed a TM cell-like genotypic profile, became phagocytic, and responded to dexamethasone stimulation, characteristic of TM cells. After transplantation into naive mouse eyes, ADSCs and ADSC-TM cells integrated into the TM tissue, expressed TM cell markers, and maintained normal IOP, outflow facility, and extracellular matrix. Cell migration and affinity results indicated that the chemokine pair CXCR4/SDF1 may play an important role in ADSC-TM cell homing. Our study demonstrates the possibility of applying autologous or allogeneic ADSCs and ADSC-TM cells as a potential treatment to restore TM structure and function in glaucoma.

摘要

小梁网(TM)是一种维持眼内压(IOP)在生理范围内的眼组织。青光眼患者的 TM 细胞减少,并且经常伴有 IOP 升高。为了建立一种基于干细胞的方法来恢复 TM 功能并使 IOP 正常化,我们诱导人脂肪来源的干细胞(ADSCs)在体外分化为 TM 细胞。这些 ADSC-TM 细胞表现出 TM 细胞样的基因型特征,具有吞噬作用,并对 TM 细胞的特征性物质地塞米松刺激产生反应。将 ADSC 和 ADSC-TM 细胞移植到未成熟的小鼠眼中后,它们整合到 TM 组织中,表达 TM 细胞标志物,并维持正常的 IOP、流出物功能和细胞外基质。细胞迁移和亲和性结果表明,趋化因子对 CXCR4/SDF1 可能在 ADSC-TM 细胞归巢中发挥重要作用。我们的研究表明,应用自体或同种异体 ADSC 和 ADSC-TM 细胞作为恢复青光眼 TM 结构和功能的潜在治疗方法是可行的。

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