Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries
Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries
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DOI：
10.1080/03008207.2016.1245726
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发表时间：
2017-01-01
影响因子：
2.9
通讯作者：
Dudhia, Jayesh
中科院分区：
文献类型：
--
作者：
Garvican, Elaine R.;Salavati, Mazdak;Dudhia, Jayesh
目的：本研究的目的是研究正常滑液（SF）对暴露的内源性肌腱源性细胞（TDC）和肌腱细胞外基质内移植的间充质干细胞（MSC）的影响。研究方法：在同种异体或自体SF-培养基中培养来自压缩、滑膜内和拉伸、滑膜外区域的马浅趾屈肌（滑膜外）和深趾屈肌腱（DDFT）的外植体。人腿筋外植体在同种异体SF中培养。通过染色评估外植体活力。通过alamarblue（R）测定SF培养基中以及与DDFT外植体共培养的马单层MSC和TDC的增殖。用MSC或TDC重新填充无活力的天然肌腱基质（NNT），并在SF培养基中培养。对肌腱切片进行凋亡蛋白caspase-3、caspase-8和caspase-9的免疫组织化学染色。结果：接触自体或同种异体SF导致马和人肌腱中的常驻腱细胞快速死亡。SF不影响马腱外膜细胞的活力，或MSC和TDC在单层或间接外植体共培养。移植到NNT中的MSC和TDC在SF中培养时死亡。Caspase-3、-8和-9在暴露于同种异体SF的SDFT外植体中表达最高。结论：滑膜内施用的细胞用于肌腱损伤修复的功效可能是有限的，因为一旦掺入基质中，细胞变得易受SF的不利影响。这些观察结果可以解释肌腱外膜损伤和与SF接触后滑膜内肌腱愈合的成功率差，这在大多数软组织滑膜内病变中很常见。
Aim: The purpose of this study was to investigate the effect of normal synovial fluid (SF) on exposed endogenous tendon-derived cells (TDCs) and engrafted mesenchymal stem cells (MSCs) within the tendon extracellular matrix. Methods: Explants from equine superficial digital flexor (extra-synovial) and deep digital flexor tendons (DDFTs) from the compressed, intra-synovial and the tensile, extrasynovial regions were cultured in allogeneic or autologous SF-media. Human hamstring explants were cultured in allogeneic SF. Explant viability was assessed by staining. Proliferation of equine monolayer MSCs and TDCs in SF-media and co-culture with DDFT explants was determined by alamarblue (R). Non-viable Native Tendon matrices (NNTs) were re-populated with MSCs or TDCs and cultured in SF-media. Immunohistochemical staining of tendon sections for the apoptotic proteins caspase-3, -8, and -9 was performed. Results: Contact with autologous or allogeneic SF resulted in rapid death of resident tenocytes in equine and human tendon. SF did not affect the viability of equine epitenon cells, or of MSCs and TDCs in the monolayer or indirect explant co-culture. MSCs and TDCs, engrafted into NNTs, died when cultured in SF. Caspase-3, -8, and -9 expression was the greatest in SDFT explants exposed to allogeneic SF. Conclusions: The efficacy of cells administered intra-synovially for tendon lesion repair is likely to be limited, since once incorporated into the matrix, cells become vlnerable to the adverse effects of SF. These observations could account for the poor success rate of intra-synovial tendon healing following damage to the epitenon and contact with SF, common with most soft tissue intra-synovial pathologies.