Zhou CM, Bao CY, Ma FF, Li M, Ha XQ. Effects of microenvironmental engineering on the stemness of human umbilical cord mesenchymal stem cells. World J Stem Cells 2026; 18(7): 120910 [DOI: 10.4252/wjsc.120910]
Corresponding Author of This Article
Xiao-Qin Ha, PhD, Department of Clinical Laboratory, The 940th Hospital of Joint Logistics Support Force of Chinese PLA, No. 333 South Binhe Middle Road, Qilihe District, Lanzhou 730050, Gansu Province, China. 331879547@qq.com
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Engineering, Biomedical
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review-article
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Zhou CM, Bao CY, Ma FF, Li M, Ha XQ. Effects of microenvironmental engineering on the stemness of human umbilical cord mesenchymal stem cells. World J Stem Cells 2026; 18(7): 120910 [DOI: 10.4252/wjsc.120910]
World J Stem Cells. Jul 26, 2026; 18(7): 120910 Published online Jul 26, 2026. doi: 10.4252/wjsc.120910
Effects of microenvironmental engineering on the stemness of human umbilical cord mesenchymal stem cells
Cun-Min Zhou, Cheng-Yuan Bao, Fei-Fei Ma, Meng Li, Xiao-Qin Ha
Cun-Min Zhou, Cheng-Yuan Bao, Fei-Fei Ma, Meng Li, Xiao-Qin Ha, Department of Clinical Laboratory, The 940th Hospital of Joint Logistics Support Force of Chinese PLA, Lanzhou 730050, Gansu Province, China
Cun-Min Zhou, Department of Clinical Laboratory, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Cun-Min Zhou, Cheng-Yuan Bao, Xiao-Qin Ha, School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Fei-Fei Ma, College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, Gansu Province, China
Meng Li, Department of Medicine, Northwest Minzu University, Lanzhou 730030, Gansu Province, China
Author contributions: Zhou CM, Bao CY, Ma FF, Li M, and Ha XQ designed the research and conceptualized the review; Zhou CM and Bao CY performed the literature search and wrote the manuscript; Ma FF and Li M contributed to the analysis of the literature and prepared the figures and tables; Ha XQ supervised the project and revised the manuscript; and all authors have read and approved the final version of the manuscript.
AI contribution statement: The authors used DeepSeek for language polishing and grammar correction. All AI-assisted outputs were reviewed and approved by the authors. The authors take full responsibility for the accuracy, integrity, and originality of this manuscript.
Supported by the National Natural Science Foundation of China, No. 82360800; Gansu Provincial Science and Technology Major Project-Social Development Field, No. 25ZDFA007; Natural Science Fund of Gansu Province, No. 22JR11RA019 and No. 25JRRA571; and Foundation of the First Hospital of Lanzhou University, No. ldyyyn2019-94.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xiao-Qin Ha, PhD, Department of Clinical Laboratory, The 940th Hospital of Joint Logistics Support Force of Chinese PLA, No. 333 South Binhe Middle Road, Qilihe District, Lanzhou 730050, Gansu Province, China. 331879547@qq.com
Received: March 13, 2026 Revised: April 8, 2026 Accepted: May 15, 2026 Published online: July 26, 2026 Processing time: 134 Days and 5 Hours
Abstract
Human umbilical cord mesenchymal stem cells (hUC-MSCs) have emerged as highly promising seed cells in regenerative medicine due to advantages such as wide availability, noninvasive collection, strong proliferative capacity, and low immunogenicity. However, the inevitable cellular senescence and loss of stemness during in vitro expansion critically compromise their clinical efficacy. Recent research has shifted focus to the supportive microenvironment. This review elaborates on an emerging strategy, the engineered microenvironment, which aims to effectively maintain and enhance hUC-MSCs stemness by mimicking and manipulating the physical, chemical, and biological signals of the stem cell niche. The article details the key roles and molecular mechanisms of physical factors (e.g., hypoxia, mechanical stimulation, and three-dimensional culture), chemical signals (small molecules and cytokines), and biomaterial scaffolds in regulating hUC-MSCs stemness. It further explores the application potential and enhanced therapeutic efficacy of this strategy in disease models such as bone repair, nerve regeneration, and endometrial repair. Finally, the review outlines challenges, including standardization and scalability. We propose future directions integrating cutting-edge technologies such as artificial intelligence, multi-omics analysis, and smart responsive materials. The aim is to provide new perspectives and a theoretical basis for developing more efficient hUC-MSCs clinical application strategies.
Core Tip: Human umbilical cord mesenchymal stem cells (hUC-MSCs) face stemness loss during in vitro expansion, limiting therapeutic efficacy. This review highlights the engineered microenvironment as a pivotal strategy to overcome this bottleneck. By recapitulating the stem cell niche via physical (hypoxia, three-dimensional architecture, and mechanics), chemical (small molecules and cytokines), and biomaterial signals, stemness can be effectively preserved. These approaches enhance hUC-MSCs proliferation, multipotency, and paracrine function, boosting their regenerative potential in disease models. This review offers a theoretical foundation for advancing standardized, microenvironment-based strategies to optimize hUC-MSCs for clinical translation in regenerative medicine.
