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同种异体间充质干细胞移植治疗犬干眼症

Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca.

作者信息

Bittencourt Maura K W, Barros Michele A, Martins João Flávio P, Vasconcellos Jose Paulo C, Morais Bruna P, Pompeia Celine, Bittencourt Matheus Domingues, Evangelho Karine Dos Santos, Kerkis Irina, Wenceslau Cristiane V

机构信息

Department of Ophthalmology, Universidade Estadual de Campinas (UNICAMP) , Campinas, SP , Brazil.

† Regenera Medicina Veterinária Avançada , Campinas, SP , Brazil.

出版信息

Cell Med. 2016 Oct 18;8(3):63-77. doi: 10.3727/215517916X693366. eCollection 2016 Dec 3.

Abstract

Keratoconjunctivitis sicca (KCS) is a dysfunction in tear production associated with clinical signs, which include conjunctival hyperemia, ocular discharge, discomfort, pain, and, eventually, corneal vascularization and pigmentation. Immunosuppressive drugs are routinely administrated for long periods to treat KCS but with side effects and limited results. Evaluation of the clinical benefits of intralacrimal transplantation of allogeneic mesenchymal stem cells (MSCs) in dogs with mild-moderate and severe KCS was done. A total of 24 eyes with KCS from 15 dogs of different breeds were enrolled in the present study. A single transplantation of MSCs (1 × 10) directly into lacrimal glands (dorsal and third eyelid) was performed. The Schirmer tear tests (STTs) and ocular surface improvements were used to assess short- and long-term effects of these cells. The STTs were carried out on day 0 (before MSCs transplantation) and on days 7, 14, 21, and 28, as well as 6 and 12 months after MSC transplantation. Our data demonstrate that allogeneic MSC transplantation in KCS dogs is safe since no adverse effects were observed immediately after transplantation and in short- and long-term follow-ups. A statistically significant increase in the STT and ocular surface improvements was found in all eyes studied. In all the eyes with mild-moderate KCS, STT values reverted to those of healthy eyes, while in eyes with severe KCS, although complete reversion was not found, there was improvement in tear production and in other clinical signs. Our study shows that a single dose of a low number of MSCs can be used to treat KCS in dogs. In contrast to immunosuppressive drug use, MSC transplantation has an effect over a long period (up to 12 months), even after a single administration, and does not require daily drug administration.

摘要

干眼症(KCS)是一种与临床症状相关的泪液分泌功能障碍,这些症状包括结膜充血、眼部分泌物、不适、疼痛,最终还会出现角膜血管化和色素沉着。免疫抑制药物通常需要长期常规使用来治疗KCS,但存在副作用且效果有限。本研究评估了同种异体间充质干细胞(MSCs)泪腺内移植对轻度 - 中度和重度KCS犬的临床益处。本研究共纳入了来自15只不同品种犬的24只患有KCS的眼睛。将MSCs(1×10)直接单次移植到泪腺(背侧和第三眼睑)。使用泪液分泌试验(STTs)和眼表改善情况来评估这些细胞的短期和长期效果。在第0天(MSCs移植前)、第7、14、21和28天以及MSCs移植后6个月和12个月进行泪液分泌试验。我们的数据表明,KCS犬同种异体MSCs移植是安全的,因为在移植后即刻以及短期和长期随访中均未观察到不良反应。在所有研究的眼睛中,泪液分泌试验和眼表改善情况均有统计学意义的增加。在所有轻度 - 中度KCS的眼睛中,泪液分泌试验值恢复到健康眼睛的水平,而在重度KCS的眼睛中,虽然未发现完全恢复,但泪液分泌和其他临床症状有所改善。我们的研究表明,单剂量低数量的MSCs可用于治疗犬的KCS。与使用免疫抑制药物相比,MSCs移植即使单次给药后也能在很长一段时间(长达12个月)内发挥作用,且无需每日给药。

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