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滑膜液和髌下脂肪垫来源间充质基质细胞的特性:组织来源和炎症刺激的影响

Characterisation of synovial fluid and infrapatellar fat pad derived mesenchymal stromal cells: The influence of tissue source and inflammatory stimulus.

作者信息

Garcia John, Wright Karina, Roberts Sally, Kuiper Jan Herman, Mangham Chas, Richardson James, Mennan Claire

机构信息

The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, SY10 7AG, UK.

Institute for Science &Technology in Medicine, Keele University, Keele, Staffordshire, ST5 5BG, UK.

出版信息

Sci Rep. 2016 Apr 13;6:24295. doi: 10.1038/srep24295.

Abstract

The infrapatellar fat pad (FP) and synovial fluid (SF) in the knee serve as reservoirs of mesenchymal stromal cells (MSCs) with potential therapeutic benefit. We determined the influence of the donor on the phenotype of donor matched FP and SF derived MSCs and examined their immunogenic and immunomodulatory properties before and after stimulation with the pro-inflammatory cytokine interferon-gamma (IFN-γ). Both cell populations were positive for MSC markers CD73, CD90 and CD105, and displayed multipotency. FP-MSCs had a significantly faster proliferation rate than SF-MSCs. CD14 positivity was seen in both FP-MSCs and SF-MSCs, and was positively correlated to donor age but only for SF-MSCs. Neither cell population was positive for the co-stimulatory markers CD40, CD80 and CD86, but both demonstrated increased levels of human leukocyte antigen-DR (HLA-DR) following IFN-γ stimulation. HLA-DR production was positively correlated with donor age for FP-MSCs but not SF-MSCs. The immunomodulatory molecule, HLA-G, was constitutively produced by both cell populations, unlike indoleamine 2, 3-dioxygenase which was only produced following IFN-γ stimulation. FP and SF are accessible cell sources which could be utilised in the treatment of cartilage injuries, either by transplantation following ex-vivo expansion or endogenous targeting and mobilisation of cells close to the site of injury.

摘要

膝关节中的髌下脂肪垫(FP)和滑液(SF)是间充质基质细胞(MSC)的储存库,具有潜在的治疗益处。我们确定了供体对与供体匹配的FP和SF来源的MSC表型的影响,并在促炎细胞因子干扰素-γ(IFN-γ)刺激前后检查了它们的免疫原性和免疫调节特性。两种细胞群体的MSC标志物CD73、CD90和CD105均呈阳性,并表现出多能性。FP-MSC的增殖速度明显快于SF-MSC。在FP-MSC和SF-MSC中均可见CD14阳性,且仅与SF-MSC的供体年龄呈正相关。两种细胞群体均未检测到共刺激标志物CD40、CD80和CD86呈阳性,但在IFN-γ刺激后均显示人类白细胞抗原-DR(HLA-DR)水平升高。对于FP-MSC,HLA-DR的产生与供体年龄呈正相关,而对于SF-MSC则不然。免疫调节分子HLA-G由两种细胞群体组成性产生,与仅在IFN-γ刺激后产生的吲哚胺2,3-双加氧酶不同。FP和SF是可获取的细胞来源,可通过体外扩增后移植或内源性靶向和动员损伤部位附近的细胞用于治疗软骨损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fc3/4829842/223d5edb60ce/srep24295-f1.jpg

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