Normal Cell Differentiation Potential of Cancer Stem Cells Without Reprogramming Pluripotent Factors: a Novel Strategy in Stem Cell-Based Therapy for Tissue Regeneration

Stem cells hold great promise for tissue regeneration and have the potential to treat many incurable degenerative diseases. Cancer stem cells (CSCs), or cancer initiating cells, have the ability to self-renew and differentiate into heterogeneous lineages of cancer cells. Current stem cell therapies face limitations, such as limited stem cell sources, time consumption, tumor formation, and immune rejection upon allogeneic transplantation. Allogeneic stem cell treatments simplify stem cell manufacturing and reduce transplant time, but their therapeutic potential is limited by human leukocyte antigen (HLA)-matched donors. CSCs retain characteristics essential for tissue regeneration. However, several limitations hinder cancer stem cell reprogramming with pluripotent factors. The development of 3D culture models for tissue imitating extracellular matrix in cancer cell lines aims to enhance CSC enrichment. This mini-review focuses on a new strategy for treating incurable degenerative diseases involving in vitro and in vivo 3D cancer models and the induced differentiation of CSCs into mature normal cell types. This allows tissue survival without immune rejection and offers a safe alternative to cancer stem cell reprogramming with pluripotent factors. In conclusion, preservation and banking of allogeneic CSCs offer an alternative, readily available, and safe strategy that can be used to facilitate stem cell-based cell therapy.干细胞在组织再生领域极具应用前景，并有潜力治疗诸多难治性退行性疾病。癌症干细胞（Cancer Stem Cells，CSCs），又称肿瘤起始细胞，具备自我更新能力，并可分化为异质性肿瘤细胞谱系。当前干细胞疗法仍存在诸多局限，例如干细胞来源有限、制备耗时、存在致瘤风险，以及同种异体移植时引发的免疫排斥反应。同种异体干细胞疗法可简化干细胞制备流程并缩短移植耗时，但其治疗潜力受限于人类白细胞抗原（Human Leukocyte Antigen，HLA）配型相合的供体来源。癌症干细胞保留了组织再生所需的关键特性，然而诸多局限阻碍了利用多能因子对癌症干细胞进行重编程的研究。针对肿瘤细胞系中模拟细胞外基质的仿生组织3D培养模型的开发，旨在提升癌症干细胞的富集效率。本简要综述聚焦于一种治疗难治性退行性疾病的全新策略，该策略借助体外与体内3D肿瘤模型，诱导癌症干细胞分化为成熟的正常细胞类型。该策略可实现组织存活且不引发免疫排斥，同时为利用多能因子重编程癌症干细胞提供了安全的替代方案。综上所述，同种异体癌症干细胞的保存与库藏，可为基于干细胞的细胞治疗提供一种易得、安全的替代策略，助力相关细胞疗法的推广应用。