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间充质干细胞来源的分泌组与细胞外囊泡:肿瘤治疗与临床应用中的前景与挑战

英文原题:Mesenchymal stem cells-derived secretome and extracellular vesicles: perspective and challenges in cancer therapy and clinical applications.

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Mesenchymal stem cells-derived secretome and extracellular vesicles: perspective and challenges in cancer therapy and clinical applications.

PubMed 2023/02/17(内容时间) Clin Transl Oncol Q3 · IF 2.7(JCR 2025)

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中文摘要

干细胞疗法被视为治疗多种疾病的一种有前景的方法,但在癌症领域,临床研究结果仍相当有限。间充质干细胞、神经干细胞和胚胎干细胞与炎症信号密切相关,临床试验中主要被用作载体,将信号递送至肿瘤生态位并加以调控。尽管这些干细胞显示出一定治疗潜力,仍面临若干挑战,包括细胞分离、免疫抑制潜能和致瘤性。

此外,监管和伦理问题也限制了其在多个国家和地区的应用。间充质干细胞(MSC)具有自我更新能力,并可分化为多种细胞类型,且伦理限制较少,因此已成为成人干细胞医学中的重要工具。细胞外囊泡(EV)、分泌组和外泌体在细胞间通讯中发挥关键作用,有助于维持生理稳态并影响疾病发生。由于免疫原性低、可生物降解、毒性低,且能够跨越生物屏障转运生物活性物质,EV和外泌体凭借其免疫学特性被视为干细胞治疗的替代方案。MSC来源的EV、外泌体和分泌组在治疗人类疾病时表现出组织再生、抗炎和免疫调节作用。本综述概述以MSC来源外泌体、分泌组和EV为基础的无细胞疗法范式,并重点讨论其在抗癌治疗中的应用潜力,以期降低免疫原性和毒性风险。深入研究MSC可能为癌症患者的有效治疗带来新机遇。

展开英文摘要原文

Stem cell-based therapies have been foreshowed as a promising therapeutic approach for the treatment of several diseases.

However, in the cancer context, results obtained from clinical studies were found to be quite limited. Deeply implicated in inflammatory cues, Mesenchymal, Neural, and Embryonic Stem Cells have mainly been used in clinical trials as a vehicle to deliver and stimulate signals in tumors niche. Although these stem cells have shown some therapeutical promises, they still face several challenges, including their isolation, immunosuppression potential, and tumorigenicity.

In addition, regulatory and ethical concerns limit their use in several countries. Mesenchymal stem cells (MSC) have emerged as a gold standard adult stem cell medicine tool due to their distinctive characteristics, such as self-renewal and potency to differentiate into numerous cell types with lower ethical restrictions. Secreted extracellular vesicles (EVs), secretomes, and exosomes play a crucial role in mediating cell-to-cell communication to maintain physiological homeostasis and influence pathogenesis.

Due to their low immunogenicity, biodegradability, low toxicity, and ability to transfer bioactive cargoes across biological barriers, EVs and exosomes were considered an alternative to stem cell therapy through their immunological features. MSCs-derived EVs, exosomes, and secretomes showed regenerative, anti-inflammatory, and immunomodulation properties while treating human diseases.

In this review, we provide an overview of the paradigm of MSCs derived exosomes, secretome, and EVs cell-free-based therapies, we will focus on MSCs-derived components in anti-cancer treatment with decreased risk of immunogenicity and toxicity. Astute exploration of MSCs may lead to a new opportunity for efficient therapy for patients with cancer.

论文信息

作者
Gemayel J、Chaker D、El Hachem G、Mhanna M、Salemeh R、Hanna C、Harb F、Ibrahim A
第一作者单位
Faculty of Health Sciences, Balamand University, Beirut, Lebanon.
通讯作者单位
Reviva Stem Cell Platform for Research and Applications Center, Bsalim, Lebanon. charbelk3@hotmail.com.
文献类型
综述
期刊
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2023 Jul
原文标识
PubMed 36808392 · DOI 10.1007/s12094-023-03115-7