{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:07:14Z","timestamp":1767712034197,"version":"3.48.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI20C0386"],"award-info":[{"award-number":["HI20C0386"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013129","name":"Ministry of SMEs and Startups","doi-asserted-by":"publisher","award":["S3283968"],"award-info":[{"award-number":["S3283968"]}],"id":[{"id":"10.13039\/501100013129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["22C0608L1"],"award-info":[{"award-number":["22C0608L1"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015098","name":"Seoul Metropolitan Government Seoul National University Boramae Medical Center","doi-asserted-by":"publisher","award":["04-2024-0010"],"award-info":[{"award-number":["04-2024-0010"]}],"id":[{"id":"10.13039\/501100015098","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center","award":["04-2025-0000"],"award-info":[{"award-number":["04-2025-0000"]}]},{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Tissue Eng Regen Med"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>In this study, RNA-seq was employed to analyze MSC transcriptomes from BM, AD, and UC tissues. UC MSCs were isolated using enzymatic digestion or the Minimal Cube Explant (MCE) method (smumf cells), and transcriptomes of early (P3\u20134) and late (P10) passages of smumf cells were compared. Differentially expressed genes (DEGs) were identified, followed by transcription factor (TF) and pathway analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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-\u03baB1, and pathways, including glycolysis, cholesterol biosynthesis, and TNF-\u03b1 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 UC MSCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>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. These findings underscore their potential as a reliable cell source for therapeutic applications and encourage further exploration of their clinical application.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13770-025-00765-2","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T12:52:18Z","timestamp":1763988738000},"page":"157-173","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.1007","volume":"23","author":[{"given":"Min Ji","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyungtaek","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sungho","family":"Won","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-5442","authenticated-orcid":false,"given":"Chris Hyunchul","family":"Jo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"765_CR1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.4055\/cios.2018.10.3.271","volume":"10","author":"YZ Jin","year":"2018","unstructured":"Jin YZ, Lee JH. Mesenchymal stem cell therapy for bone regeneration. Clin Orthop Surg. 2018;10:271\u20138.","journal-title":"Clin Orthop Surg"},{"key":"765_CR2","doi-asserted-by":"publisher","first-page":"841","DOI":"10.2217\/rme-2018-0137","volume":"14","author":"D Alhattab","year":"2019","unstructured":"Alhattab D, Jamali F, Ali D, Hammad H, Adwan S, Rahmeh R, et al. An insight into the whole transcriptome profile of four tissue-specific human mesenchymal stem cells. Regen Med. 2019;14:841\u201365.","journal-title":"Regen Med"},{"key":"765_CR3","doi-asserted-by":"publisher","first-page":"8429042","DOI":"10.1155\/2018\/8429042","volume":"2018","author":"JH Kim","year":"2018","unstructured":"Kim JH, Jo CH, Kim HR, Hwang YI. Comparison of immunological characteristics of mesenchymal stem cells from the periodontal ligament, umbilical cord, and adipose tissue. Stem Cells Int. 2018;2018:8429042.","journal-title":"Stem Cells Int"},{"key":"765_CR4","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/s12015-018-9800-6","volume":"14","author":"K Camernik","year":"2018","unstructured":"Camernik K, Barlic A, Drobnic MJ, Jeras M, Zupan J. Mesenchymal stem cells in the musculoskeletal system: from animal models to human tissue regeneration? Stem Cell Rev Rep. 2018;14:346\u201369.","journal-title":"Stem Cell Rev Rep"},{"key":"765_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4055\/cios20128","volume":"13","author":"PW Yoon","year":"2021","unstructured":"Yoon PW, Kang JY, Kim CH, Lee SJ, Yoo JJ, Kim HJ, et al. Culture-expanded autologous adipose-derived mesenchymal stem cell treatment for osteonecrosis of the femoral head. Clin Orthop Surg. 2021;13:37\u201346.","journal-title":"Clin Orthop Surg"},{"key":"765_CR6","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1007\/s00441-008-0696-3","volume":"334","author":"CH Jo","year":"2008","unstructured":"Jo CH, Kim OS, Park EY, Kim BJ, Lee JH, Kang SB, et al. Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion. Cell Tissue Res. 2008;334:423\u201333.","journal-title":"Cell Tissue Res"},{"key":"765_CR7","doi-asserted-by":"publisher","first-page":"2","DOI":"10.5397\/CiSE.2012.15.2.65","volume":"15","author":"SWMY Sim","year":"2012","unstructured":"Sim SWMY, Kang JH. Differential potential of stem cells following their origin: subacromial bursa, bone marrow, umbilical cord blood. Clin Shoulder Elbow. 2012;15:2\u201365.","journal-title":"Clin Shoulder Elbow"},{"key":"765_CR8","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jcyt.2018.11.008","volume":"21","author":"VD Myneni","year":"2019","unstructured":"Myneni VD, McClain-Caldwell I, Martin D, Vitale-Cross L, Marko K, Firriolo JM, et al. Mesenchymal stromal cells from infants with simple polydactyly modulate immune responses more efficiently than adult mesenchymal stromal cells. Cytotherapy. 2019;21:148\u201361.","journal-title":"Cytotherapy"},{"key":"765_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-021-02176-1","volume":"12","author":"Y Yu","year":"2021","unstructured":"Yu Y, Valderrama AV, Han Z, Uzan G, Naserian S, Oberlin E. Human fetal liver MSCs are more effective than adult bone marrow MSCs for their immunosuppressive, immunomodulatory, and Foxp3(+) T reg induction capacity. Stem Cell Res Ther. 2021;12:1\u2013138.","journal-title":"Stem Cell Res Ther"},{"key":"765_CR10","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/430847","volume":"2015","author":"I Kalaszczynska","year":"2015","unstructured":"Kalaszczynska I, Ferdyn K. Wharton\u2019s jelly derived mesenchymal stem cells: future of regenerative medicine? Recent findings and clinical significance. Biomed Res Int. 2015;2015:430847.","journal-title":"Biomed Res Int"},{"key":"765_CR11","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1089\/ten.tea.2019.0254","volume":"26","author":"S Sahai","year":"2020","unstructured":"Sahai S, Wilkerson M, Xue H, Moreno N, Carrillo L, Flores R, et al. Wharton\u2019s jelly for augmented cleft palate repair in a rat critical-size alveolar bone defect model. Tissue Eng Part A. 2020;26:591\u2013601.","journal-title":"Tissue Eng Part A"},{"key":"765_CR12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031439","author":"I Song","year":"2022","unstructured":"Song I, Rim J, Lee J, et al. Therapeutic potential of human fetal mesenchymal stem cells in musculoskeletal disorders: a narrative review. Int J Mol Sci. 2022. https:\/\/doi.org\/10.3390\/ijms23031439.","journal-title":"Int J Mol Sci"},{"key":"765_CR13","doi-asserted-by":"publisher","first-page":"6901286","DOI":"10.1155\/2016\/6901286","volume":"2016","author":"I Arutyunyan","year":"2016","unstructured":"Arutyunyan I, Elchaninov A, Makarov A, Fatkhudinov T. Umbilical cord as prospective source for mesenchymal stem cell-based therapy. Stem Cells Int. 2016;2016:6901286.","journal-title":"Stem Cells Int"},{"key":"765_CR14","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1634\/stemcells.2007-0439","volume":"26","author":"DL Troyer","year":"2008","unstructured":"Troyer DL, Weiss ML. Wharton\u2019s jelly-derived cells are a primitive stromal cell population. Stem Cells. 2008;26:591\u20139.","journal-title":"Stem Cells"},{"key":"765_CR15","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.tibtech.2006.01.010","volume":"24","author":"JK Fraser","year":"2006","unstructured":"Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol. 2006;24:150\u20134.","journal-title":"Trends Biotechnol"},{"key":"765_CR16","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1159\/000080341","volume":"14","author":"RH Lee","year":"2004","unstructured":"Lee RH, Kim B, Choi I, Kim H, Choi HS, Suh K, et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem. 2004;14:311\u201324.","journal-title":"Cell Physiol Biochem"},{"key":"765_CR17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1089\/107632701300062859","volume":"7","author":"PA Zuk","year":"2001","unstructured":"Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7:211\u201328.","journal-title":"Tissue Eng"},{"key":"765_CR18","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-022-00440-w","author":"AY Lee","year":"2022","unstructured":"Lee AY, Jang KH, Jo CH. Minimal cube explant provides optimal isolation condition of mesenchymal stem cells from umbilical cord. Tissue Eng Regen Med. 2022;19:793\u2013807.","journal-title":"Tissue Eng Regen Med"},{"key":"765_CR19","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1002\/sctm.18-0246","volume":"8","author":"DM Wiese","year":"2019","unstructured":"Wiese DM, Ruttan CC, Wood CA, Ford BN, Braid LR. Accumulating transcriptome drift precedes cell aging in human umbilical cord-derived mesenchymal stromal cells serially cultured to replicative senescence. Stem Cells Transl Med. 2019;8:945\u201358.","journal-title":"Stem Cells Transl Med"},{"key":"765_CR20","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1007\/s13770-024-00673-x","volume":"21","author":"AY Lee","year":"2024","unstructured":"Lee AY, Park JY, Hwang SJ, Jang KH, Jo CH. Effects of late-passage small umbilical cord-derived fast proliferating cells on tenocytes from degenerative rotator cuff tears under an interleukin 1beta-induced tendinopathic environment. Tissue Eng Regen Med. 2024;21:1217\u201331.","journal-title":"Tissue Eng Regen Med"},{"key":"765_CR21","volume":"34","author":"JH Yea","year":"2023","unstructured":"Yea JH, Kim Y, Jo CH. Comparison of mesenchymal stem cells from bone marrow, umbilical cord blood, and umbilical cord tissue in regeneration of a full-thickness tendon defect in vitro and in vivo. Biochem Biophys Rep. 2023;34:101486.","journal-title":"Biochem Biophys Rep"},{"key":"765_CR22","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114\u201320.","journal-title":"Bioinformatics"},{"key":"765_CR23","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15\u201321.","journal-title":"Bioinformatics"},{"key":"765_CR24","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"DDanecek P, Bonfield JK, Liddle J, Marshall J, Ohan V, Pollard MO, et al. Twelve years of SAMtools and BCFtools. Gigascience. 2021;10:giab008.","journal-title":"Gigascience"},{"key":"765_CR25","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W. HTSeq\u2013a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31:2\u2013166-9.","journal-title":"Bioinformatics"},{"key":"765_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:12\u2013550.","journal-title":"Genome Biol"},{"key":"765_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128","volume":"14","author":"EY Chen","year":"2013","unstructured":"Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013;14:128.","journal-title":"BMC Bioinformatics"},{"key":"765_CR28","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1137\/18M1211350","volume":"80","author":"NB Erichson","year":"2020","unstructured":"Erichson NB, Zheng P, Manohar K, Brunton SL, Kutz JN, Aravkin AY. Sparse principal component analysis via variable projection. SIAM J Appl Math. 2020;80:977\u20131002.","journal-title":"SIAM J Appl Math"},{"key":"765_CR29","unstructured":"Kolde R, Kolde MR. Package \u2018pheatmap\u2019. R package. 2015;1:790."},{"key":"765_CR30","first-page":"1","volume":"224","author":"C Gene Ontology","year":"2023","unstructured":"Gene Ontology Consortium, Aleksander SA, Balhoff J, Carbon S, Cherry JM, Drabkin HJ, et al. The Gene Ontology knowledgebase in 2023. Genetics. 2023;224:1.","journal-title":"Genetics"},{"key":"765_CR31","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184:3573\u201387.","journal-title":"Cell"},{"key":"765_CR32","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184:3573\u201387.","journal-title":"Cell"},{"issue":"1","key":"765_CR33","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00441-013-1619-5","volume":"353","author":"CH Jo","year":"2013","unstructured":"Jo CH, Yoon PW, Kim H, Kang KS, Yoon KS. Comparative evaluation of in vivo osteogenic differentiation of fetal and adult mesenchymal stem cell in rat critical-sized femoral defect model. Cell Tissue Res. 2013;353:41\u201352.","journal-title":"Cell Tissue Res"},{"key":"765_CR34","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/scrt442","volume":"5","author":"PR Amable","year":"2014","unstructured":"Amable PR, Teixeira MV, Carias RB, Granjeiro JM, Borojevic R. Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton\u2019s jelly. Stem Cell Res Ther. 2014;5:2\u201353.","journal-title":"Stem Cell Res Ther"},{"key":"765_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/scd.2009.0177","volume":"19","author":"U Nekanti","year":"2010","unstructured":"Nekanti U, Rao VB, Bahirvani AG, Jan M, Totey S, Ta M. Long-term expansion and pluripotent marker array analysis of Wharton\u2019s jelly-derived mesenchymal stem cells. Stem Cells Dev. 2010;19:117\u201330.","journal-title":"Stem Cells Dev"},{"key":"765_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-020-01873-7","volume":"11","author":"DM Wiese","year":"2020","unstructured":"Wiese DM, Braid LR. Transcriptome profiles acquired during cell expansion and licensing validate mesenchymal stromal cell lineage genes. Stem Cell Res Ther. 2020;11:1\u2013357.","journal-title":"Stem Cell Res Ther"},{"key":"765_CR37","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1634\/stemcells.2008-0372","volume":"26","author":"P Dufourcq","year":"2008","unstructured":"Dufourcq P, Descamps B, Tojais NF, Leroux L, Oses P, Daret D, et al. Secreted frizzled-related protein-1 enhances mesenchymal stem cell function in angiogenesis and contributes to neovessel maturation. Stem Cells. 2008;26:2991\u20133001.","journal-title":"Stem Cells"},{"key":"765_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2020.115444","volume":"137","author":"H Gu","year":"2020","unstructured":"Gu H, Shi S, Xiao F, Huang Z, Xu J, Chen G, et al. Mir-1-3p regulates the differentiation of mesenchymal stem cells to prevent osteoporosis by targeting secreted frizzled-related protein 1. Bone. 2020;137:115444.","journal-title":"Bone"},{"key":"765_CR39","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.gendis.2014.09.007","volume":"1","author":"B Popov","year":"2014","unstructured":"Popov B, Petrov N. pRb-E2F signaling in life of mesenchymal stem cells: Cell cycle, cell fate, and cell differentiation. Genes Dis. 2014;1:174\u201387.","journal-title":"Genes Dis."},{"key":"765_CR40","doi-asserted-by":"publisher","first-page":"28556","DOI":"10.1074\/jbc.M111.256180","volume":"286","author":"C Buhrmann","year":"2011","unstructured":"Buhrmann C, Mobasheri A, Busch F, Aldinger C, Stahlmann R, Montaseri A, et al. Curcumin modulates nuclear factor kappaB (NF-kappaB)-mediated inflammation in human tenocytes in vitro: role of the phosphatidylinositol 3-kinase\/Akt pathway. J Biol Chem. 2011;286:28556\u201366.","journal-title":"J Biol Chem"},{"issue":"4","key":"765_CR41","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1007\/s13577-022-00711-7","volume":"35","author":"Q Mo","year":"2022","unstructured":"Mo Q, Zhang W, Zhu A, Backman LJ, Chen J. Regulation of osteogenic differentiation by the pro-inflammatory cytokines IL-1beta and TNF-alpha: current conclusions and controversies. Hum Cell. 2022;35:957\u201371.","journal-title":"Hum Cell"},{"key":"765_CR42","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.757830","volume":"9","author":"N Zhang","year":"2021","unstructured":"Zhang N, Utsunomiya T, Lin T, Kohno Y, Ueno M, Maruyama M, et al. Mesenchymal stem cells and NF-kappaB sensing interleukin-4 over-expressing mesenchymal stem cells are equally effective in mitigating particle-associated chronic inflammatory bone loss in mice. Front Cell Dev Biol. 2021;9:757830.","journal-title":"Front Cell Dev Biol"},{"key":"765_CR43","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/cells10082042","volume":"10","author":"C Kaltschmidt","year":"2021","unstructured":"Kaltschmidt C, Greiner JFW, Kaltschmidt B. The transcription factor NF-kappaB in stem cells and development. Cells. 2021;10:8.","journal-title":"Cells"},{"key":"765_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00311","volume":"8","author":"PD Denechaud","year":"2017","unstructured":"Denechaud PD, Fajas L, Giralt A. E2F1, a novel regulator of metabolism. Front Endocrinol (Lausanne). 2017;8:311.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"765_CR45","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1089\/ars.2009.2755","volume":"12","author":"MR Afzal","year":"2010","unstructured":"Afzal MR, Haider H, Idris NM, Jiang S, Ahmed RP, Ashraf M. Preconditioning promotes survival and angiomyogenic potential of mesenchymal stem cells in the infarcted heart via NF-kappaB signaling. Antioxid Redox Signal. 2010;12:693\u2013702.","journal-title":"Antioxid Redox Signal"},{"key":"765_CR46","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1089\/scd.2009.0365","volume":"19","author":"H Hemeda","year":"2010","unstructured":"Hemeda H, Jakob M, Ludwig AK, Giebel B, Lang S, Brandau S. Interferon-gamma and tumor necrosis factor-alpha differentially affect cytokine expression and migration properties of mesenchymal stem cells. Stem Cells Dev. 2010;19:693\u2013706.","journal-title":"Stem Cells Dev."},{"key":"765_CR47","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/ijms22179531","volume":"22","author":"L Lopez-Garcia","year":"2021","unstructured":"Lopez-Garcia L, Castro-Manrreza ME. TNF-alpha and IFN-gamma participate in improving the Immunoregulatory capacity of mesenchymal stem\/stromal cells: importance of cell-cell contact and extracellular vesicles. Int J Mol Sci. 2021;22:17.","journal-title":"Int J Mol Sci"},{"key":"765_CR48","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/stem.2298","volume":"34","author":"JD Anderson","year":"2016","unstructured":"Anderson JD, Johansson HJ, Graham CS, Vesterlund M, Pham MT, Bramlett CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappab signaling. Stem Cells. 2016;34:601\u201313.","journal-title":"Stem Cells"},{"key":"765_CR49","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41419-019-1336-4","volume":"10","author":"T Vigo","year":"2019","unstructured":"Vigo T, La Rocca C, Faicchia D, Procaccini C, Ruggieri M, Salvetti M, et al. IFNbeta enhances mesenchymal stromal (Stem) cells immunomodulatory function through STAT1-3 activation and mTOR-associated promotion of glucose metabolism. Cell Death Dis. 2019;10:2\u201385.","journal-title":"Cell Death Dis"},{"key":"765_CR50","doi-asserted-by":"publisher","first-page":"9221","DOI":"10.1016\/S0140-6736(00)02386-2","volume":"355","author":"N Lila","year":"2000","unstructured":"Lila N, Carpentier A, Amrein C, Khalil-Daher I, Dausset J, Carosella ED. Implication of HLA-G molecule in heart-graft acceptance. Lancet. 2000;355:9221\u20132138.","journal-title":"Lancet"},{"key":"765_CR51","doi-asserted-by":"publisher","first-page":"70","DOI":"10.3109\/14653249.2011.613926","volume":"14","author":"HM Yang","year":"2012","unstructured":"Yang HM, Sung JH, Choi YS, Lee HJ, Roh CR, Kim J, et al. Enhancement of the immunosuppressive effect of human adipose tissue-derived mesenchymal stromal cells through HLA-G1 expression. Cytotherapy. 2012;14:70\u20139.","journal-title":"Cytotherapy"},{"key":"765_CR52","doi-asserted-by":"publisher","first-page":"2865","DOI":"10.1634\/stemcells.2007-1028","volume":"26","author":"ML Weiss","year":"2008","unstructured":"Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, et al. Immune properties of human umbilical cord Wharton\u2019s jelly-derived cells. Stem Cells. 2008;26:2865\u201374.","journal-title":"Stem Cells"},{"key":"765_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-022-03178-3","volume":"13","author":"C Xu","year":"2022","unstructured":"Xu C, Feng C, Huang P, Li Y, Liu R, Liu C, et al. TNFalpha and IFNgamma rapidly activate PI3K-AKT signaling to drive glycolysis that confers mesenchymal stem cells enhanced anti-inflammatory property. Stem Cell Res Ther. 2022;13:491.","journal-title":"Stem Cell Res Ther"},{"key":"765_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-021-02194-z","volume":"12","author":"W Yan","year":"2021","unstructured":"Yan W, Diao S, Fan Z. The role and mechanism of mitochondrial functions and energy metabolism in the function regulation of the mesenchymal stem cells. Stem Cell Res Ther. 2021;12:140.","journal-title":"Stem Cell Res Ther"},{"issue":"3","key":"765_CR55","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/s12015-024-10681-y","volume":"20","author":"Y Liu","year":"2024","unstructured":"Liu Y, Wang L, Ai J, Li K. Mitochondria in mesenchymal stem cells: key to fate determination and therapeutic potential. Stem Cell Rev Rep. 2024;20:617\u201336.","journal-title":"Stem Cell Rev Rep."},{"key":"765_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.606781","volume":"12","author":"C Jorgensen","year":"2021","unstructured":"Jorgensen C, Khoury M. Musculoskeletal progenitor\/stromal cell-derived mitochondria modulate cell differentiation and therapeutical function. Front Immunol. 2021;12:606781.","journal-title":"Front Immunol"},{"key":"765_CR57","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.580070","volume":"8","author":"L Ren","year":"2020","unstructured":"Ren L, Chen X, Chen X, Li J, Cheng B, Xia J. Mitochondrial dynamics: fission and fusion in fate determination of mesenchymal stem cells. Front Cell Dev Biol. 2020;8:580070.","journal-title":"Front Cell Dev Biol"}],"container-title":["Tissue Engineering and Regenerative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-025-00765-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13770-025-00765-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-025-00765-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:03:19Z","timestamp":1767711799000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13770-025-00765-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["765"],"URL":"https:\/\/doi.org\/10.1007\/s13770-025-00765-2","relation":{},"ISSN":["1738-2696","2212-5469"],"issn-type":[{"type":"print","value":"1738-2696"},{"type":"electronic","value":"2212-5469"}],"subject":[],"published":{"date-parts":[[2025,11,24]]},"assertion":[{"value":"16 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Chris Jo owns shares of AcesoStem Biostrategies Inc. The other authors indicated no potential conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was approved by the Institutional Review Board at Seoul Metropolitan Government Seoul National University Boramae Medical Center (IRB No.06\u20132012-78).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}