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免疫抑制药物对脂肪和骨髓来源间充质干细胞活力和敏感性的影响。

Effects of immunosuppressive drugs on viability and susceptibility of adipose- and bone marrow-derived mesenchymal stem cells.

机构信息

Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, PA , USA ; Department of Surgery, Shiga Medical Center for Adults , Moriyama , Japan.

Department of Plastic Surgery, University of Pittsburgh , Pittsburgh, PA , USA.

出版信息

Front Immunol. 2015 Apr 16;6:131. doi: 10.3389/fimmu.2015.00131. eCollection 2015.


DOI:10.3389/fimmu.2015.00131
PMID:25932028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4399413/
Abstract

The immunomodulatory potential of cell therapies using adipose-derived stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) has been studied in vascularized composite allotransplantation (VCA). Most cell therapy-based experimental and clinical protocols integrate some degree of recipient conditioning/induction with antibodies or other immunosuppressive agents. We investigated the susceptibility of ASCs and BM-MSCs to anti-lymphocyte serum (ALS) and tacrolimus. Rat ASCs and BM-MSCs were exposed to varying concentrations of tacrolimus and ALS in vitro. Serum from ALS-treated animals was added to cell cultures. Viability, susceptibility, and cytotoxicity parameters were evaluated. ALS inhibited ASC and BM-MSC viability and susceptibility in vitro in a dose-dependent manner. ASCs were more susceptible to both ALS and tacrolimus than BM-MSCs. Trypsinized and adherent ASCs were significantly smaller than BM-MSCs. This is the first report on the viability and susceptibility characteristics of BM-MSCs or ASCs to collateral effects of ALS and tacrolimus. These in vitro insights may impact choice of cell type as well as concomitant conditioning agents and the logistical coordination of the timing, dosing, and frequency of drug or cell therapy in solid organ transplantation or VCA protocols.

摘要

脂肪来源的干细胞 (ASCs) 和骨髓来源的间充质干细胞 (BM-MSCs) 的细胞治疗的免疫调节潜力已在血管化复合组织同种异体移植 (VCA) 中进行了研究。大多数基于细胞治疗的实验和临床方案都将一定程度的受体调理/诱导与抗体或其他免疫抑制剂结合使用。我们研究了 ASCs 和 BM-MSCs 对抗淋巴细胞血清 (ALS) 和他克莫司的敏感性。将大鼠 ASCs 和 BM-MSCs 暴露于体外不同浓度的他克莫司和 ALS 中。向细胞培养物中添加来自 ALS 处理动物的血清。评估了存活率、敏感性和细胞毒性参数。ALS 以剂量依赖性方式抑制 ASC 和 BM-MSC 的体外活力和敏感性。ASCs 比 BM-MSCs 更容易受到 ALS 和他克莫司的影响。胰蛋白酶消化和贴壁的 ASCs 明显小于 BM-MSCs。这是关于 BM-MSCs 或 ASCs 对 ALS 和他克莫司的副作用的存活和敏感性特征的首次报告。这些体外研究结果可能会影响细胞类型的选择以及伴随的调理剂,以及实体器官移植或 VCA 方案中药物或细胞治疗的时间、剂量和频率的逻辑协调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/f24ad10f804e/fimmu-06-00131-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/d12c7f44cf51/fimmu-06-00131-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/bce3d6d379ca/fimmu-06-00131-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/01f47f31a4d5/fimmu-06-00131-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/87378cc8fee0/fimmu-06-00131-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/7c43d76f9b43/fimmu-06-00131-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/f24ad10f804e/fimmu-06-00131-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/d12c7f44cf51/fimmu-06-00131-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/bce3d6d379ca/fimmu-06-00131-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/01f47f31a4d5/fimmu-06-00131-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/87378cc8fee0/fimmu-06-00131-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/7c43d76f9b43/fimmu-06-00131-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1694/4399413/f24ad10f804e/fimmu-06-00131-g006.jpg

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本文引用的文献

[1]
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Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion.

Front Immunol. 2012-9-26

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Ann Surg. 2013-2

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