Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells.
Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells.
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DOI：
10.1007/s00125-018-4713-0
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发表时间：
2018-11
期刊：
影响因子：
8.2
通讯作者：
Harmsen MC
中科院分区：
文献类型：
--
作者：
Hajmousa G;Przybyt E;Pfister F;Paredes-Juarez GA;Moganti K;Busch S;Kuipers J;Klaassen I;van Luyn MJA;Krenning G;Hammes HP;Harmsen MC
脂肪组织来源的基质细胞（ASC）的免疫调节能力与旨在逆转组织功能障碍（例如由糖尿病引起的组织功能障碍）的下一代细胞疗法相关。视网膜毛细血管的周细胞脱落是糖尿病视网膜病变和随后的异常血管生成的基础。我们在早产儿视网膜病变小鼠中玻璃体内注射 ASCs 作为临床糖尿病视网膜病变模型，研究了 ASCs 的周细胞功能。此外，ASC 通过旁分泌信号影响其环境。为此，我们评估了培养的 ASC (ASC-Cme) 条件培养基对高糖 (HG) 刺激的牛视网膜内皮细胞 (BREC) 的免疫调节能力。 ASC 增强并稳定了视网膜血管生成，并与毛细血管共定位于周细胞特异性位置。这表明培养的 ASC 在视网膜微血管中发挥近分泌信号。 ASC-Cme 在培养的 BREC 中减轻了 HG 诱导的氧化应激及其随后以 NF-κB 依赖性方式上调的下游靶标。从功能上讲，用 ASC-Cme 处理后，单核细胞对活化 BREC 单层的粘附也减少，并与粘附相关基因（如 SELE、ICAM1 和 VCAM1）表达下降相关。 ASC-Cme 免疫调节 HG 攻击的 BREC 的能力与 ASC 在 HG 培养基中预处理的时间长度有关。来自长期暴露于 HG 培养基的 ASC 的条件培养基能够使 HG 攻击的 BREC 正常化至正常葡萄糖水平。相比之下，暴露于 HG 培养基较短时间的 ASC 条件培养基则没有这种效果。我们的结果表明，ASC 的 HG 预处理方式决定了它们的免疫调节特性，从而决定了糖尿病视网膜病变治疗的潜在结果。
The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequent aberrant angiogenesis. We investigated the pericytic function of ASCs after intravitreal injection of ASCs in mice with retinopathy of prematurity as a model for clinical diabetic retinopathy. In addition, ASCs influence their environment by paracrine signalling. For this, we assessed the immunomodulatory capacity of conditioned medium from cultured ASCs (ASC-Cme) on high glucose (HG)-stimulated bovine retinal endothelial cells (BRECs). ASCs augmented and stabilised retinal angiogenesis and co-localised with capillaries at a pericyte-specific position. This indicates that cultured ASCs exert juxtacrine signalling in retinal microvessels. ASC-Cme alleviated HG-induced oxidative stress and its subsequent upregulation of downstream targets in an NF-κB dependent fashion in cultured BRECs. Functionally, monocyte adhesion to the monolayers of activated BRECs was also decreased by treatment with ASC-Cme and correlated with a decline in expression of adhesion-related genes such as SELE, ICAM1 and VCAM1. The ability of ASC-Cme to immunomodulate HG-challenged BRECs is related to the length of time for which ASCs were preconditioned in HG medium. Conditioned medium from ASCs that had been chronically exposed to HG medium was able to normalise the HG-challenged BRECs to normal glucose levels. In contrast, conditioned medium from ASCs that had been exposed to HG medium for a shorter time did not have this effect. Our results show that the manner of HG preconditioning of ASCs dictates their immunoregulatory properties and thus the potential outcome of treatment of diabetic retinopathy.
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影响因子：
4.4
作者：
Cai, Jun;Kehoe, Oksana;Boulton, Michael E.
通讯作者：
Boulton, Michael E.
影响因子：
2.8
作者：
Abu El-Asrar, Ahmed M.;Struyf, Sofie;Van Damme, Jo
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Van Damme, Jo
影响因子：
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作者：
Demircan, N.;Safran, B. G.;Sizmaz, S.
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Sizmaz, S.
影响因子：
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作者：
DICORLETO, PE;DELAMOTTE, CA
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DELAMOTTE, CA
影响因子：
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作者：
AbuElAsrar, AM;VanDamme, J;Missotten, L
通讯作者：
Missotten, L