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World J Stem Cells. Apr 26, 2026; 18(4): 117414
Published online Apr 26, 2026. doi: 10.4252/wjsc.v18.i4.117414
Adipose-derived mesenchymal stem cells: Source-dependent heterogeneity, translational challenges, and emerging precision strategies
Qing Xu, Huan Li, Jian-Chuan Deng, Nan Zhang
Qing Xu, Huan Li, Jian-Chuan Deng, Nan Zhang, Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
Co-first authors: Qing Xu and Huan Li.
Co-corresponding authors: Jian-Chuan Deng and Nan Zhang.
Author contributions: Xu Q and Li H contributed equally to this work as co-first authors. Xu Q collected and reviewed the literature and drafted the manuscript; Li H assisted with literature collection and manuscript revision; Deng JC and Zhang N contributed equally as co-corresponding authors. Deng JC conceptualized the study and revised the manuscript; Zhang N designed the study and supervised the manuscript preparation. All authors read and approved the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Nan Zhang, Department of Hematology, The Second Affiliated Hospital of Chongqing Medical University, No. 288 Tianwen Avenue, Nan’an District, Chongqing 400010, China. zhangnan@hospital.cqmu.edu.cn
Received: December 8, 2025
Revised: January 25, 2026
Accepted: February 25, 2026
Published online: April 26, 2026
Processing time: 135 Days and 3.2 Hours
Abstract

Adipose-derived mesenchymal stem cells (ADSCs) have emerged as an important cell source in regenerative medicine because of their accessibility, abundance, multilineage differentiation potential, and paracrine activity. However, ADSCs are not biologically uniform, and their properties are strongly influenced by donor-related factors, anatomical origin of adipose tissue, and technical procedures used for cell isolation, expansion, and characterization. This review summarizes current advances in defining the source-dependent characteristics of ADSCs, with particular emphasis on donor age, metabolic status, adipose depot specificity, isolation methods, culture conditions, and source-related molecular and functional heterogeneity. Evidence from transcriptomic, epigenetic, immunophenotypic, and secretome studies indicates that ADSCs from different sources may differ substantially in proliferation and differentiation capacity, immunomodulatory activity, and therapeutic performance. Major challenges remain in translating these findings into clinical practice, including donor variability, inconsistent manufacturing workflows, lack of standardized potency assays, and insufficient integration of source-stratified strategies into product development. Emerging directions such as single-cell and multi-omics profiling, cell-free secretome-based therapeutics, and source-aware manufacturing frameworks may improve precision and reproducibility in ADSC-based therapies. A clearer understanding of ADSC source dependency will be essential for optimizing donor selection, improving product consistency, and advancing the safe and effective clinical translation of regenerative medicine applications.

Keywords: Adipose-derived mesenchymal stem cells; Source dependency; Donor heterogeneity; Adipose tissue depot; Secretome; Regenerative medicine

Core Tip: Adipose-derived mesenchymal stem cells are a heterogeneous cell population whose biological and therapeutic properties are strongly influenced by donor background, adipose tissue origin, and manufacturing conditions. This review summarizes source-dependent differences in proliferation, differentiation, immunomodulation, and secretome composition, and highlights key challenges in standardization and clinical translation. Emerging approaches, including single-cell profiling, multi-omics analysis, and cell-free secretome-based therapy, may improve the precision and reproducibility of adipose-derived mesenchymal stem cell-based regenerative strategies.