Cell Origin and Microenvironment: The Players of Differentiation Capacity in Human Mesenchymal Stem Cells

• Published in: Tissue & cell 2025-04, Vol.93, p.102709, Article 102709
• Main Authors: Hoseini, Seyed Mehdi, Montazeri, Fateme
• Format: Article
• Language: English
• Subjects: differentiation; Mesenchymal stem cells; microenvironment; paracrine secretions; regenerative medicine
• ISSN: 0040-8166
• DOI: 10.1016/j.tice.2024.102709

Mesenchymal stem cells (MSCs) have several important properties that make them desirable for regenerative medicine. These properties include immunomodulatory ability, growth factor production, and differentiation into various cell types. Despite extensive research and promising results in clinical trials, our understanding of MSC biology, their mechanism of action, and their targeted and routine use in clinics is limited. Differentiation of human MSCs (hMSCs) is a complex process influenced by various elements such as growth factors, pharmaceutical compounds, microRNAs, 3D scaffolds, and mechanical and electrical stimulation. Research has shown that different culture conditions can affect the differentiation potential of hMSCs obtained from multiple fetal and adult sources. Additionally, it seems that what affects the differentiation capacities of these cells is their secretory characteristics, which are influenced by the origin of the cells and the local microenvironment where the cells are located. The review can provide insights into the microenvironment-based mechanisms involved in MSC differentiation, which can be valuable for future therapeutic applications. [Display omitted] •Fetal and adult human mesenchymal stem cells (hMSCs) exhibit hierarchical differences that impact their differentiation potential.•These hierarchical differences, stemming from various cell sources, result in hMSCs having variable paracrine secretions.•The distinct microenvironments created by different secretome influence the differentiation potential of MSCs.