{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T19:22:22Z","timestamp":1788895342533,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T00:00:00Z","timestamp":1733875200000},"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":["RS-2023-KH140392"],"award-info":[{"award-number":["RS-2023-KH140392"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin-6 (IL-6) expression in mesenchymal stem cells (MSCs) has been shown to play a pivotal role in modulating cartilage regeneration and immune responses, particularly in the context of diseases that involve both degenerative processes and inflammation, such as osteoarthritis (OA). However, the precise mechanism through which IL-6 and other immune-regulatory factors influence the therapeutic efficacy of autologous adipose-derived stem cells (ASCs) transplantation in OA treatment remains to be fully elucidated. This study aims to investigate the relationship between IL-6 expression in autologous ASCs isolated from OA patients and their impact on immune modulation, particularly focusing on the regulation of Receptor Activator of Nuclear factor Kappa-\u0392 Ligand (RANKL), a key mediator of immune-driven cartilage degradation in OA. Autologous ASCs were isolated from the stromal vascular fraction (SVF) of adipose tissue obtained from 22 OA patients. The isolated ASCs were cultured and characterized using reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to the phenotype and immune regulatory factors of MSCs. Based on IL-6 expression levels, ASCs were divided into high and low IL-6 expression groups. These groups were then co-cultured with activated peripheral blood mononuclear cells (PBMCs) to evaluate their immune-modulatory capacity, including the induction of regulatory T cells, inhibition of immune cell proliferation, and regulation of key cytokines, such as interferon-gamma (IFN-\u03b3). Additionally, RANKL expression, a critical factor in osteoclastogenesis and cartilage degradation, was assessed in both ASC groups. High IL-6-expressing ASCs demonstrated a significantly greater capacity to inhibit immune cell proliferation and IFN-\u03b3 production compared to their low IL-6-expressing counterparts under co-culture conditions. Moreover, the group of ASCs with high IL-6 expression showed a marked reduction in RANKL expression, suggesting enhanced potential to control osteoclast activity and subsequent cartilage defect in OA. Conclusion: Autologous ASCs with elevated IL-6 expression exhibit enhanced immunomodulatory properties, particularly in regulating over-activated immune response and reducing osteoclastogenesis through RANKL suppression. These findings indicate that selecting ASCs based on IL-6 expression could enhance the therapeutic efficacy of ASC-based treatments for OA by mitigating immune-driven joint inflammation and cartilage degradation, potentially slowing disease progression.<\/jats:p>","DOI":"10.3390\/cells13242046","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T12:58:49Z","timestamp":1733921929000},"page":"2046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Elevated IL-6 Expression in Autologous Adipose-Derived Stem Cells Regulates RANKL Mediated Inflammation in Osteoarthritis"],"prefix":"10.3390","volume":"13","author":[{"given":"Hyun-Joo","family":"Lee","sequence":"first","affiliation":[{"name":"Stem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Stem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of Korea"},{"name":"N-BIOTEK, Inc., 402-803, Technopark, 655, Pyeongcheon-ro, Bucheon-si 14502, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon jeong","family":"Noh","sequence":"additional","affiliation":[{"name":"Stem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of Korea"},{"name":"N-BIOTEK, Inc., 402-803, Technopark, 655, Pyeongcheon-ro, Bucheon-si 14502, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song Yi","family":"Lee","sequence":"additional","affiliation":[{"name":"Stem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Ae","family":"Yoo","sequence":"additional","affiliation":[{"name":"Stem Cell R&D Center, N-BIOTEK, Inc., 104-706, Technopark Ssangyong 3Cha, 397, Seokcheon-ro, Bucheon-si 14449, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7907-7283","authenticated-orcid":false,"given":"Samuel Jaeyoon","family":"Won","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Sang","family":"Jeon","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of Korea"},{"name":"School of Medicine, Inha University, Incheon 22013, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hoon","family":"Baek","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2455-5230","authenticated-orcid":false,"given":"Dong Jin","family":"Ryu","sequence":"additional","affiliation":[{"name":"Orthopedic Surgery, Inha University Hospital, Incheon 22332, Republic of Korea"},{"name":"School of Medicine, Inha University, Incheon 22013, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nrrheum.2014.44","article-title":"The individual and socioeconomic impact of osteoarthritis","volume":"10","author":"Hunter","year":"2014","journal-title":"Nat. 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