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

Molecular therapy. Oncology Pub Date : 2024-11-20 eCollection Date: 2024-12-19 DOI:10.1016/j.omton.2024.200907
Marcel Costa-Garcia, Laura Moya-Borrego, Ramon Alemany Bonastre, Rafael Moreno Olié
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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. In vivo 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.

经血来源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。
溶瘤病毒(OVs)是一种很有前景的癌症治疗方法,尽管它们的全身给药面临着重大挑战。间充质干细胞由于其致瘤性而成为克服这些障碍的潜在载体。本研究探讨了经血源性间充质干细胞(MenSCs)作为OVs的载体在癌症治疗中的应用,重点探讨了通过不同的培养条件来增强其疗效。从不同年龄的供体中分离MenSCs,在常氧和缺氧条件下培养,粘附能力不同。增殖实验和rna测序分析表明,缺氧条件显著提高了MenSCs的增殖和肿瘤迁移能力,这表明与细胞分裂和肿瘤趋向性相关的基因上调。使用肺腺癌小鼠模型进行的体内研究证实,缺氧条件下的MenSCs具有优越的肿瘤归巢能力。该研究还证明了从一次经血中建立一个主细胞库和工作细胞库的可行性。这些发现表明,缺氧条件下的MenSCs作为OV载体可能非常有效,通过增强肿瘤靶向性和治疗效果,可能在癌症治疗中获得更好的临床结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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