Comparative Transcriptomic Profiling of Mesenchymal Stem Cells from Distinct Tissue Origins and Isolation Methods - Stability and Immunomodulatory Signature of Umbilical Cord-Derived Smumf Cells

Sep 30, 2026

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Mesenchymal stem cells (MSCs) from bone marrow, adipose tissue, and umbilical cord show therapeutic promise, yet their transcriptomic profiles differ with tissue origin, passage stage, and isolation approach, hindering clinical standardization. RNA-seq was used to compare MSC transcriptomes from BM, AD, and UC, including enzymatically isolated UCMSCs and Minimal Cube Explant-derived smumf cells at early (P3–4) and late (P10) passages. Results reveal fetal MSCs with distinct gene-expression programs, enriched pathways in smumf cells, and strong transcriptional stability across passages.

LanguageEnglish

CategoryResearch & Report

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Pages17

Reading Time43 min

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Abstract

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Tissue Eng Regen Med (2026) 23(1):157–173 Online ISSN 2212-5469 [https://doi.org/10.1007/s13770-025-00765-2](https://doi.org/10.1007/s13770-025-00765-2) ORIGINAL ARTICLE Comparative Transcriptomic Proﬁling of Mesenchymal Stem Cells from Distinct Tissue Origins and Isolation Methods Highlights the Stability and Immunomodulatory Signature of Umbilical Cord-Derived Smumf Cells Min Ji Lee1,2 • Kyungtaek Park3,8 • Sungho Won3,4,5,7 • Chris Hyunchul Jo1,2,6 Received: 16 May 2025/Revised: 4 August 2025/Accepted: 9 September 2025/Published online: 24 November 2025 􀀂 Korean Tissue Engineering and Regenerative Medicine Society 2025 Abstract BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) exhibit therapeutic potential in regenerative medicine. However, their properties, including transcriptomic proﬁles, vary based on tissue origin, passage stage, and isolation method, complicating their clinical standardization. Addressing these unresolved differences requires comprehensive approaches, such as RNA sequencing, to analyze transcriptomic proﬁles in detail. METHODS: In this study, RNA-seq was employed to analyze MSC transcriptomes from BM, AD, and UC tissues. UCMSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes of early (P3–4) and late (P10) passages of smumf cells were compared. Differentially expressed genes (DEGs) were identiﬁed, followed by transcription factor (TF) and pathway analyses. RESULTS: Fetal MSCs (UC and smumf cells) exhibited distinct transcriptomic proﬁles compared to adult MSCs (BM and AD), with 2,208 upregulated and 2,594 downregulated DEGs. Key transcription factors, such as E2F1 and NF-jB1, and pathways, including glycolysis, cholesterol biosynthesis, and TNF-a signaling, were enriched in fetal MSCs. smumf cells demonstrated transcriptomic stability between early and late passages, with only 12 DEGs identiﬁed. Additionally, smumf cells showed enhanced innate immune responses and cholesterol metabolism compared to enzymatically isolated UCMSCs. CONCLUSION: This study provides a comprehensive transcriptomic comparison of MSCs, highlighting the superior transcriptional stability, immunomodulatory capacity, and metabolic ﬂexibility of fetal MSCs, particularly smumf cells. Min Ji Lee and Kyungtaek Park are the co-ﬁrst authors. & & 1 2 3 Sungho Won [won1@snu.ac.kr](won1@snu.ac.kr) Chris Hyunchul Jo [chrisjo@snu.ac.kr](chrisjo@snu.ac.kr) Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 07061, Korea Department of Translational Medicine, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea Institute of Health and Environment, Seoul National University, 1Gwanak-ro, Gwanak-gu, Seoul 08826, Korea 4 Interdisciplinary Program of Bioinformatics, College of Natural Sciences, Seoul National University, 1Gwanak-ro, Gwanak-gu, Seoul 08826, Korea 5 Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, 1Gwanak-ro, Gwanak-gu, Seoul 08826, Korea 6 Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea 7 RexSoft Corp, 1Gwanak-ro, Gwanak-gu, Seoul 08826, Korea 8 Department of Statistics (Institute of Applied Statistics), Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju 54896, Korea These ﬁndings underscore their potential as a reliable cell source for therapeutic applications and encourage further exploration of their clinical application. Keywords Mesenchymal stem cells 􀀂 RNA sequencing 􀀂 Immunomodulation 􀀂 Cell therapy 1 Introduction Mesenchymal stem cells (MSCs) have therapeutic potential due to their ability to differentiate, promote tissue repair, modul

FAQs

What study question addresses MSC variability across sources?

The study examines how MSC transcriptomic profiles vary with tissue origin and isolation method, and how these differences affect clinical standardization.

How were UC-derived smumf cells isolated and compared?

UCMSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes were compared between early (P3–4) and late (P10) passages.

What key transcriptomic findings differentiate fetal from adult MSCs?

Fetal MSCs (UC and smumf cells) showed distinct transcriptomic profiles versus adult MSCs (BM and AD), with thousands of differentially expressed genes and enrichment of transcription factors and metabolic and inflammatory pathways.

Sep 30, 2026

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