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载药牙龈间充质基质细胞(GinPa-MSCs)抑制口腔鳞状细胞癌的体外增殖。

Drug Loaded Gingival Mesenchymal Stromal Cells (GinPa-MSCs) Inhibit In Vitro Proliferation of Oral Squamous Cell Carcinoma.

机构信息

StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133, Milan, Italy.

Department of Medicine and Surgery, Dental School, University of Insubria, Varese, Italy.

出版信息

Sci Rep. 2017 Aug 24;7(1):9376. doi: 10.1038/s41598-017-09175-4.


DOI:10.1038/s41598-017-09175-4
PMID:28839168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5571047/
Abstract

Human mesenchymal stromal cells (MSCs) have been widely investigated both for regenerative medicine and their antinflammatory/immunomodulatory capacity. However, their ability to home pathological tissues suggested the development of strategies for using MSCs as carrier to deliver drug into tumor microenvironment. MSCs obtained from different tissues can be loaded in vitro with anti-cancer drugs by a simple procedures. In this report, we studied MSCs isolated and expanded from gingival papilla (GinPa-MSCs), by testing their ability to uptake and release three important anti-neoplastic drugs: Paclitaxel (PTX), Doxorubicin (DXR) and Gemcitabine (GCB). The efficacy of drugs releasing GinPa-MSCs was studied on a pancreatic cancer cell line and confirmed in vitro against a line of tongue squamous cell carcinoma (SCC154). Our results demonstrated that GinPa-MSCs efficiently incorporate the drugs and then released them in active form and in sufficient amount to produce a dramatic inhibition of squamous cell carcinoma growth in vitro. If compared with other MSCs sources, the collection of GinPa-MSCs is poorly invasive and cells can be easily expanded and efficiently loaded with anti cancer drugs. In particular, gemcitabine loaded GinPa-MSCs provide a good "cell-mediated drug delivery system" for a future potential application in the context of the oral oncology.

摘要

人间质基质细胞(MSCs)已广泛研究,无论是为了再生医学还是其抗炎/免疫调节能力。然而,它们向病理组织归巢的能力表明,可以开发利用 MSCs 作为载体将药物递送到肿瘤微环境的策略。可以通过简单的程序将来自不同组织的 MSCs 在体外加载抗癌药物。在本报告中,我们研究了从牙龈乳头(GinPa-MSCs)分离和扩增的 MSCs,通过测试它们摄取和释放三种重要的抗肿瘤药物:紫杉醇(PTX)、多柔比星(DXR)和吉西他滨(GCB)的能力。在胰腺癌细胞系上研究了释放药物的 GinPa-MSCs 的功效,并在体外针对舌鳞状细胞癌(SCC154)系进行了验证。我们的结果表明,GinPa-MSCs 能够有效地摄取药物,然后以活性形式释放药物,并以足够的量释放药物,从而在体外显著抑制鳞状细胞癌的生长。与其他 MSCs 来源相比,GinPa-MSCs 的采集侵入性较小,细胞易于扩增,并能有效地加载抗癌药物。特别是,负载吉西他滨的 GinPa-MSCs 为未来在口腔肿瘤学中的潜在应用提供了良好的“细胞介导药物传递系统”。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/8029f0388f19/41598_2017_9175_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/1d02392266b5/41598_2017_9175_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/da580947699d/41598_2017_9175_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/3122baf8f629/41598_2017_9175_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/d2a0ecf98e8e/41598_2017_9175_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/cbf43d81ed0d/41598_2017_9175_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/8029f0388f19/41598_2017_9175_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/1d02392266b5/41598_2017_9175_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/da580947699d/41598_2017_9175_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/3122baf8f629/41598_2017_9175_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/d2a0ecf98e8e/41598_2017_9175_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/cbf43d81ed0d/41598_2017_9175_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a31/5571047/8029f0388f19/41598_2017_9175_Fig6_HTML.jpg

相似文献

[1]
Drug Loaded Gingival Mesenchymal Stromal Cells (GinPa-MSCs) Inhibit In Vitro Proliferation of Oral Squamous Cell Carcinoma.

Sci Rep. 2017-8-24

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Fluorescent Immortalized Human Adipose Derived Stromal Cells (hASCs-TS/GFP+) for Studying Cell Drug Delivery Mediated by Microvesicles.

Anticancer Agents Med Chem. 2017-11-24

[2]
Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma.

World J Gastroenterol. 2016-8-21

[3]
Chemotherapy with gemcitabine plus cisplatin in patients with advanced thymic squamous cell carcinoma: Evaluation of efficacy and toxicity.

Thorac Cancer. 2015-8-4

[4]
Cell-mediated drug delivery by gingival interdental papilla mesenchymal stromal cells (GinPa-MSCs) loaded with paclitaxel.

Expert Opin Drug Deliv. 2016-6

[5]
Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery.

Clin Exp Dermatol. 2016-6

[6]
A Phase II Study of Gemcitabine, Vincristine, and Cisplatin As Second-Line Treatment for Patients with Advanced Soft Tissue Sarcoma.

Medicine (Baltimore). 2015-10

[7]
Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells.

Cytotherapy. 2015-12

[8]
Biweekly gemcitabine and paclitaxel in patients with relapsed or metastatic squamous cell carcinoma of the head and neck.

Avicenna J Med. 2015

[9]
Oral squamous cell carcinoma in a patient treated with long-term pegylated liposomal doxorubicin for recurrent ovarian cancer.

BMJ Case Rep. 2015-1-14

[10]
TRAIL on trial: preclinical advances in cancer therapy.

Trends Mol Med. 2013-9-26

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