Symbiosis Centre for Stem Cell Research (SCSCR) and Symbiosis School of Biological Sciences (SSBS), SIU, Lavale, Pune 412115, India.
ACS Biomater Sci Eng. 2022 Nov 14;8(11):4673-4696. doi: 10.1021/acsbiomaterials.2c00484. Epub 2022 Oct 4.
Cancer has recently been the second leading cause of death worldwide, trailing only cardiovascular disease. Cancer stem cells (CSCs), represented as tumor-initiating cells (TICs), are mainly liable for chemoresistance and disease relapse due to their self-renewal capability and differentiating capacity into different types of tumor cells. The intricate molecular mechanism is necessary to elucidate CSC's chemoresistance properties and cancer recurrence. Establishing efficient strategies for CSC maintenance and enrichment is essential to elucidate the mechanisms and properties of CSCs and CSC-related therapeutic measures. Current approaches are insufficient to mimic the chemical and physical conditions for the maintenance and growth of CSC and yield unreliable research results. Biomaterials are now widely used for simulating the bone marrow microenvironment. Biomaterial-based three-dimensional (3D) approaches for the enrichment of CSC provide an excellent promise for future drug discovery and elucidation of molecular mechanisms. In the future, the biomaterial-based model will contribute to a more operative and predictive CSC model for cancer therapy. Design strategies for materials, physicochemical cues, and morphology will offer a new direction for future modification and new methods for studying the CSC microenvironment and its chemoresistance property. This review highlights the critical roles of the microenvironmental cues that regulate CSC function and endow them with drug resistance properties. This review also explores the latest advancement and challenges in biomaterial-based scaffold structure for therapeutic approaches against CSC chemoresistance. Since the recent entry of extracellular vesicles (EVs), cell-derived nanostructures, have opened new avenues of investigation into this field, which, together with other more conventionally studied signaling pathways, play an important role in cell-to-cell communication. Thus, this review further explores the subject of EVs in-depth. This review also discusses possible future biomaterial and biomaterial-EV-based models that could be used to study the tumor microenvironment (TME) and will provide possible therapeutic approaches. Finally, this review concludes with potential perspectives and conclusions in this area.
癌症最近已成为全球第二大死亡原因，仅次于心血管疾病。癌症干细胞（CSC），表现为肿瘤起始细胞（TIC），主要由于其自我更新能力和分化为不同类型肿瘤细胞的能力而导致化疗耐药和疾病复发。阐明 CSC 化疗耐药性和癌症复发的复杂分子机制是必要的。建立有效的 CSC 维持和富集策略对于阐明 CSC 的机制和特性以及 CSC 相关的治疗措施至关重要。目前的方法不足以模拟 CSC 的维持和生长的化学和物理条件，从而产生不可靠的研究结果。生物材料现在广泛用于模拟骨髓微环境。基于生物材料的三维（3D）方法用于 CSC 的富集为未来的药物发现和阐明分子机制提供了极好的前景。在未来，基于生物材料的模型将有助于建立更具操作性和预测性的癌症治疗 CSC 模型。材料、物理化学线索和形态的设计策略将为未来的修饰提供新的方向，并为研究 CSC 微环境及其化疗耐药性提供新的方法。本文综述了调节 CSC 功能并赋予其耐药性的微环境线索的关键作用。本文还探讨了用于治疗 CSC 化疗耐药性的基于生物材料的支架结构的最新进展和挑战。由于细胞外囊泡（EVs）的最近进入，细胞衍生的纳米结构为该领域的研究开辟了新途径，这些结构与其他更传统研究的信号通路一起，在细胞间通讯中发挥着重要作用。因此，本文进一步深入探讨了 EVs 的主题。本文还讨论了可能用于研究肿瘤微环境（TME）的未来生物材料和生物材料-EV 模型，并提供了可能的治疗方法。最后，本文对该领域的潜在观点和结论进行了总结。
