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大剂量类固醇治疗后人类滑膜间充质干细胞功能的时间依赖性恢复:病例报告和实验室研究。

Time-Dependent Recovery of Human Synovial Membrane Mesenchymal Stem Cell Function After High-Dose Steroid Therapy: Case Report and Laboratory Study.

机构信息

Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.

出版信息

Am J Sports Med. 2018 Mar;46(3):695-701. doi: 10.1177/0363546517741307. Epub 2017 Dec 11.

DOI:10.1177/0363546517741307
PMID:29227146
Abstract

BACKGROUND

The use of mesenchymal stem cells from various tissue sources to repair injured tissues has been explored over the past decade in large preclinical models and is now moving into the clinic.

PURPOSE

To report the case of a patient who exhibited compromised mesenchymal stem cell (MSC) function shortly after use of high-dose steroid to treat Bell's palsy, who recovered 7 weeks after therapy.

STUDY DESIGN

Case report and controlled laboratory study.

METHODS

A patient enrolled in a first-in-human clinical trial for autologous implantation of a scaffold-free tissue engineered construct (TEC) derived from synovial MSCs for chondral lesion repair had a week of high-dose steroid therapy for Bell's palsy. Synovial tissue was harvested for MSC preparation after a 3-week recovery period and again at 7 weeks after therapy.

RESULTS

The MSC proliferation rates and cell surface marker expression profiles from the 3-week sample met conditions for further processing. However, the cells failed to generate a functional TEC. In contrast, MSCs harvested at 7 weeks after steroid therapy were functional in this regard. Further in vitro studies with MSCs and steroids indicated that the effect of in vivo steroids was likely a direct effect of the drug on the MSCs.

CONCLUSION

This case suggests that MSCs are transiently compromised after high-dose steroid therapy and that careful consideration regarding timing of MSC harvest is critical.

CLINICAL RELEVANCE

The drug profiles of MSC donors and recipients must be carefully monitored to optimize opportunities to successfully repair damaged tissues.

摘要

背景

过去十年中,人们在大型临床前模型中探索了使用各种组织来源的间充质干细胞来修复受损组织,现在这项技术正在进入临床阶段。

目的

报告一例患者在使用大剂量类固醇治疗贝尔氏麻痹后不久出现间充质干细胞(MSC)功能受损的情况,在治疗 7 周后恢复。

研究设计

病例报告和对照实验室研究。

方法

一名患者参加了一项自体植入无支架组织工程构建体(TEC)的首次人体临床试验,该构建体源自滑膜 MSC,用于软骨损伤修复,在接受为期 3 周的恢复期后,因贝尔氏麻痹接受了一周的高剂量类固醇治疗。滑膜组织在治疗后 7 周时再次收获用于 MSC 准备。

结果

第 3 周样本的 MSC 增殖率和细胞表面标志物表达谱符合进一步处理的条件。然而,这些细胞未能生成功能性 TEC。相比之下,在类固醇治疗后 7 周收获的 MSC 在这方面具有功能。进一步的 MSC 和类固醇体外研究表明,体内类固醇的作用可能是药物对 MSC 的直接作用。

结论

本病例提示大剂量类固醇治疗后 MSC 会短暂受损,因此仔细考虑 MSC 采集的时间至关重要。

临床相关性

必须仔细监测 MSC 供体和受体的药物谱,以优化成功修复受损组织的机会。

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