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工程化间充质干细胞用于癌症治疗:机遇、临床应用与挑战

Engineered Mesenchymal Stem Cells as Treatment for Cancers: Opportunities, Clinical Applications and Challenges.

作者信息

Shamsul Kamal Aishah Amirah, Fakiruddin Kamal Shaik, Bobbo Khadijat Abubakar, Ling King Hwa, Vidyadaran Sharmili, Abdullah Syahril

机构信息

UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Selangor, Malaysia.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.

出版信息

Malays J Med Sci. 2024 Oct;31(5):56-82. doi: 10.21315/mjms2024.31.5.5. Epub 2024 Oct 8.

DOI:10.21315/mjms2024.31.5.5
PMID:39416732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11477465/
Abstract

The insufficient and unspecific target of classical chemotherapies often leads to therapy resistance and cancer recurrence. Over the past decades, discoveries about mesenchymal stem cell (MSC) biology have provided new potential approaches to improve cancer therapy. Researchers have utilised the multipotent, regenerative and immunosuppressive qualities of MSCs and tropisms towards inflammatory, hypoxic and malignant sites in various therapeutic applications. Although MSC-based therapies have generally been demonstrated safe, their effectiveness remains limited when these cells are used alone. However, through genetic engineering, researchers have proven that MSCs can be modified to have specialised delivery roles to increase their therapeutic efficacy in cancer treatment. They can be made to overexpress therapeutic proteins through viral or non-viral genetic modification, which enhances their innate properties. Nevertheless, these engineering strategies must be optimised to increase therapeutic efficacy and targeting effectiveness while minimising any loss of MSC function. This review underscores the cutting-edge methods for engineering MSCs, discusses their promise and the difficulties in translating them into clinical settings, and offers some prospective suggestions for the future on achieving their full therapeutic potential.

摘要

传统化疗的靶点不足且缺乏特异性,常常导致治疗耐药和癌症复发。在过去几十年里,关于间充质干细胞(MSC)生物学的发现为改善癌症治疗提供了新的潜在方法。研究人员在各种治疗应用中利用了间充质干细胞的多能性、再生能力和免疫抑制特性,以及它们对炎症、缺氧和恶性部位的趋向性。尽管基于间充质干细胞的治疗总体上已被证明是安全的,但当单独使用这些细胞时,其有效性仍然有限。然而,通过基因工程,研究人员已经证明,可以对间充质干细胞进行改造,使其具有特殊的递送作用,以提高其在癌症治疗中的疗效。通过病毒或非病毒基因改造,可以使它们过度表达治疗性蛋白质,从而增强其固有特性。尽管如此,这些工程策略必须进行优化,以提高治疗效果和靶向有效性,同时尽量减少间充质干细胞功能的任何损失。这篇综述强调了工程化间充质干细胞的前沿方法,讨论了它们的前景以及转化为临床应用的困难,并为未来充分发挥其治疗潜力提供了一些前瞻性建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f075/11477465/69c456b30f31/05mjms3105_raf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f075/11477465/3f2ddf7da42a/05mjms3105_raf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f075/11477465/69c456b30f31/05mjms3105_raf2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f075/11477465/3f2ddf7da42a/05mjms3105_raf1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f075/11477465/69c456b30f31/05mjms3105_raf2.jpg

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本文引用的文献

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Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities.癌症进展和治疗耐药中的外泌体:分子见解与治疗机遇
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Metastasis Related Epithelial-Mesenchymal Transition Signature Predicts Prognosis and Response to Chemotherapy in Acute Myeloid Leukemia.转移相关上皮-间充质转化特征可预测急性髓系白血病的预后和化疗反应。
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Targeting TRAIL Death Receptors in Triple-Negative Breast Cancers: Challenges and Strategies for Cancer Therapy.
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Genetic profiling of human bone marrow mesenchymal stromal cells after expansion in clinical grade human platelet lysate.在临床级人血小板裂解物中扩增后的人骨髓间充质基质细胞的基因谱分析。
Front Bioeng Biotechnol. 2022 Oct 12;10:1008271. doi: 10.3389/fbioe.2022.1008271. eCollection 2022.
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Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties.抗癌药物:提高稳定性、药代动力学和药效学特性的最新策略。
Molecules. 2022 Aug 25;27(17):5436. doi: 10.3390/molecules27175436.
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Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review.间充质干细胞在再生医学中的临床应用:叙述性综述。
Stem Cell Res Ther. 2022 Jul 28;13(1):366. doi: 10.1186/s13287-022-03054-0.
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Exosomes in multiple myeloma: from bench to bedside.多发性骨髓瘤中的外泌体:从基础到临床。
Blood. 2022 Dec 8;140(23):2429-2442. doi: 10.1182/blood.2021014749.
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Epithelial-Mesenchymal Transition-Inducing Factors Involved in the Progression of Lung Cancers.参与肺癌进展的上皮-间质转化诱导因子
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Cancer statistics, 2022.癌症统计数据,2022 年。
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Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines.CD133+癌干细胞的化疗增敏作用增强了表达TRAIL的间充质干细胞对非小细胞肺癌细胞系的作用。
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