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用于培养月经血源性间充质干细胞与溶瘤腺病毒联合用于癌症治疗的优化方案。

Optimized protocol for culturing menstrual blood-derived MSCs for combination with oncolytic adenoviruses in cancer treatment.

作者信息

Costa-Garcia Marcel, Moya-Borrego Laura, Alemany Bonastre Ramon, Moreno Olié Rafael

机构信息

Cancer Immunotherapy Group, Oncobell and iProCURE programs, IDIBELL-Institut Català d'Oncologia, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.

出版信息

Mol Ther Oncol. 2024 Nov 20;32(4):200907. doi: 10.1016/j.omton.2024.200907. eCollection 2024 Dec 19.

Abstract

Oncolytic viruses (OVs) are a promising therapeutic approach for cancer, although their systemic administration faces significant challenges. Mesenchymal stem cells have emerged as potential carriers to overcome these obstacles due to their tumor-tropic properties. This study investigates the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as carriers for OVs in cancer therapy, focusing on enhancing their efficacy through different culture conditions. MenSCs were isolated from donors of different ages and cultured under normoxic and hypoxic conditions, with varying adherence capacities. Hypoxic conditions significantly improved MenSCs proliferation and tumor migration capabilities, as demonstrated by proliferation assays and RNA-sequencing analysis, which revealed upregulation of genes related to cell division and tumor tropism. studies using a lung adenocarcinoma mouse model confirmed that hypoxia-conditioned MenSCs had superior tumor-homing abilities. The study also demonstrated the feasibility of establishing a master and working cell bank from a single menstrual blood donation. These findings suggest that hypoxia-conditioned MenSCs could be highly effective as OV carriers, potentially leading to better clinical outcomes in cancer treatment by enhancing tumor targeting and therapeutic efficacy.

摘要

溶瘤病毒(OVs)是一种很有前景的癌症治疗方法,尽管其全身给药面临重大挑战。间充质干细胞因其肿瘤趋向性特性,已成为克服这些障碍的潜在载体。本研究探讨了月经血来源的间充质干细胞(MenSCs)作为溶瘤病毒在癌症治疗中的载体的应用,重点是通过不同的培养条件提高其疗效。从不同年龄的供体中分离出MenSCs,并在常氧和低氧条件下培养,其贴壁能力各不相同。增殖试验和RNA测序分析表明,低氧条件显著提高了MenSCs的增殖和肿瘤迁移能力,揭示了与细胞分裂和肿瘤趋向性相关基因的上调。使用肺腺癌小鼠模型的研究证实,低氧预处理的MenSCs具有优异的肿瘤归巢能力。该研究还证明了从单次月经血捐献建立主细胞库和工作细胞库的可行性。这些发现表明,低氧预处理的MenSCs作为溶瘤病毒载体可能非常有效,通过增强肿瘤靶向性和治疗效果,有可能在癌症治疗中带来更好的临床结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f54e/11697545/ad1fddc9f011/fx1.jpg

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