A Novel Combined Therapeutic Approach to Endometriosis: Exosomes Derived from Human Wharton's Jelly Mesenchymal Stem Cells and Etanercept

Mahdavi R, Roya Mahdavi, Dayer D, Dian Dayer, Amari A, Afshin Amari, Zorvan Jalili, Jalili Z, Mehri Ghafourian, Ghafourian M, Maryam Farzaneh, Farzaneh M
Current Molecular Medicine · 2025 · vol. 25 · doi:10.2174/0115665240386032250914233540 · PMID:40993922 · W4414523418
article OA: closed CC0
Full text JSON View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-07-09 ⓘ

This study found that a combination of etanercept and exosomes derived from human Wharton's jelly mesenchymal stem cells synergistically reduced inflammatory cytokines and enzymes in endometriosis cells.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-07, 2026-07-09 · read from full text ⓘ

This study evaluated a combined immunomodulatory treatment using etanercept (ETN) and exosomes derived from human Wharton’s jelly mesenchymal stem cells (hWJMSC-Exo) on endometrial stromal cells collected from eutopic and ectopic endometriosis tissues and non-endometriotic controls. Endometrial stromal cells were exposed to ETN (0–40 μg/ml), hWJMSC-Exo (0–15 μg/ml), or their combination, and effects on metabolic viability (MTT) plus protein levels of TNF-α, VEGF-A, and IL-10 (ELISA) and mRNA expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 (RT-PCR) were measured over 24–72 hours. The ETN+hWJMSC-Exo combination (10 μg/ml each) reduced TNF-α, VEGF-A, and IL-10 proteins and also significantly lowered the mRNA levels of the measured remodeling/inflammatory/angiogenic and immune-regulatory markers compared with untreated groups across all cell sources (P < 0.001). The authors note that clinical validation and long-term safety require further in vivo studies with larger sample sizes. This paper is centrally about endometriosis — it tests an ETN plus hWJMSC-derived exosome combination to modulate inflammatory, angiogenic, and tissue remodeling mediators in endometriosis-derived stromal cells.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

INTRODUCTION: Endometriosis is a chronic disorder characterized by abnormal endometrial tissue growth. This study evaluates a novel combination immunomodulatory treatment involving etanercept (ETN) and exosomes derived from human Wharton's jelly mesenchymal stem cells (hWJMSC-Exo) as a promising alternative to conventional therapies for modulating inflammation in endometriosis. METHODS: Endometrial stromal cells were isolated by enzymatic digestion of eutopic (EuESCs, N = 6) and ectopic (EESCs, N = 6) tissues of endometriosis patients and non-endometriotic controls (CESCs, N = 6). hWJMSC-Exo were confirmed by flow cytometry, SEM, and DLS tests. Cells were treated with varying concentrations of ETN (0-40 μg/ml), hWJMSC-Exo (0-15 μg/ml), and their combination (E+E). IC50 values were determined using the MTT assay at 24, 48, and 72 hours. Protein levels of TNF- α, VEGF-A, and IL-10, and gene expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 were measured using ELISA and RT-PCR, respectively. RESULTS: The combination of ETN (10 μg/ml) and hWJMSC-Exo (10 μg/ml) at 24 and 48 hours, respectively, reduced protein expression of TNF-α, VEGF-A, and IL-10 in EESCs, EuESCs, and CESCs compared with untreated groups (P < 0.001). Additionally, E+E treatment significantly reduced mRNA expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 in all three groups compared to untreated groups. DISCUSSION: This combination therapy improves inflammation, angiogenesis, tissue remodeling, and immune regulation in endometriosis. However, clinical validation and long-term safety require further in vivo studies with larger sample sizes. CONCLUSION: E+E treatment synergistically reduced key cytokines and enzymes in endometriosis. This approach is a promising means of regulating inflammation.
Full text 6,474 characters · extracted from oa-doi-fallback · 6 sections · click to expand

Abstract

Introduction: Endometriosis is a chronic disorder characterized by abnormal endometrial tissue growth. This study evaluates a novel combination immunomodulatory treatment involving etanercept (ETN) and exosomes derived from human Wharton's jelly mesenchymal stem cells (hWJMSC-Exo) as a promising alternative to conventional therapies for modulating inflammation in endometriosis.

Methods

Endometrial stromal cells were isolated by enzymatic digestion of eutopic (EuESCs, N = 6) and ectopic (EESCs, N = 6) tissues of endometriosis patients and non-endometriotic controls (CESCs, N = 6). hWJMSC-Exo were confirmed by flow cytometry, SEM, and DLS tests. Cells were treated with varying concentrations of ETN (0-40 μg/ml), hWJMSC-Exo (0-15 μg/ml), and their combination (E+E). IC50 values were determined using the MTT assay at 24, 48, and 72 hours. Protein levels of TNF- α, VEGF-A, and IL-10, and gene expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 were measured using ELISA and RT-PCR, respectively.

Results

The combination of ETN (10 μg/ml) and hWJMSC-Exo (10 μg/ml) at 24 and 48 hours, respectively, reduced protein expression of TNF-α, VEGF-A, and IL-10 in EESCs, EuESCs, and CESCs compared with untreated groups (P < 0.001). Additionally, E+E treatment significantly reduced mRNA expression of MMP-2, MMP-9, MCP-1, aromatase, TSLP, and TGF-β1 in all three groups compared to untreated groups.

Discussion

This combination therapy improves inflammation, angiogenesis, tissue remodeling, and immune regulation in endometriosis. However, clinical validation and long-term safety require further in vivo studies with larger sample sizes.

Conclusion

E+E treatment synergistically reduced key cytokines and enzymes in endometriosis. This approach is a promising means of regulating inflammation.

Keywords

Combination therapy, endometriosis, etanercept, exosome, inflammation, mesenchymal stem cell, wharton jelly. [http://dx.doi.org/10.2174/0115665240311438241011052341] [PMID: 39501947] [PMID: 38375785] [http://dx.doi.org/10.3389/fendo.2022.858176] [PMID: 35784569] [PMCID: PMC9245568] [http://dx.doi.org/10.1016/j.yexcr.2025.114553] [PMID: 40216010] [http://dx.doi.org/10.3390/biom11111739] [PMID: 34827737] [http://dx.doi.org/10.3389/fonc.2019.01370] [PMID: 31921634] [http://dx.doi.org/10.1038/srep16859] [PMID: 26577912] [http://dx.doi.org/10.1093/humrep/dex067] [PMID: 28383711] [http://dx.doi.org/10.5603/gpl.103148] [PMID: 39878755] [PMID: 8923461] [PMID: 24966899] [http://dx.doi.org/10.1016/j.jri.2022.103515] [PMID: 35381481] [http://dx.doi.org/10.1016/j.ejogrb.2016.07.513] [PMID: 27544308] [http://dx.doi.org/10.3390/ph17070827] [PMID: 39065678] [http://dx.doi.org/10.1080/14712598.2024.2436094] [PMID: 39663567] [http://dx.doi.org/10.1016/j.jri.2024.104415] [PMID: 39700679] [http://dx.doi.org/10.1007/s00404-010-1543-9] [PMID: 20544212] [http://dx.doi.org/10.1016/j.ejogrb.2011.06.029] [PMID: 21741153] [http://dx.doi.org/10.1007/s00404-010-1434-0] [PMID: 20333392] [http://dx.doi.org/10.1016/j.cellimm.2024.104813] [PMID: 38364454] [http://dx.doi.org/10.1016/j.intimp.2023.110405] [PMID: 37270928] [http://dx.doi.org/10.1186/s12964-022-00853-z] [PMID: 35414084] [http://dx.doi.org/10.1038/ncomms8321] [PMID: 26084661] [http://dx.doi.org/10.2217/rme-2021-0169] [PMID: 35938412] [http://dx.doi.org/10.1007/s11356-021-18401-6] [PMID: 34993805] [http://dx.doi.org/10.34172/apb.2024.027] [PMID: 39206409] [http://dx.doi.org/10.1016/j.jri.2022.103638] [PMID: 35588629] [http://dx.doi.org/10.1186/s13287-021-02244-6] [PMID: 33761997] [http://dx.doi.org/10.1186/s13287-022-03079-5] [PMID: 35897039] [http://dx.doi.org/10.1016/j.intimp.2023.110294] [PMID: 37167639] [http://dx.doi.org/10.1016/S0015-0282(97)81391-X] [PMID: 9130884] [http://dx.doi.org/10.1373/clinchem.2008.112797] [PMID: 19246619] [http://dx.doi.org/10.1002/cpt.1827] [PMID: 32153014] [http://dx.doi.org/10.1186/s12348-023-00375-w] [PMID: 38017191] [http://dx.doi.org/10.3389/fimmu.2020.00312] [PMID: 32174918] [http://dx.doi.org/10.1007/s00404-003-0591-9] [PMID: 14745563] [http://dx.doi.org/10.1177/22840265241231722] [http://dx.doi.org/10.3390/ijms25094802] [PMID: 38732021] [PMID: 39717957] [http://dx.doi.org/10.1016/j.fertnstert.2003.09.034 ] [PMID: 15019808] [http://dx.doi.org/10.3389/fimmu.2023.1128301] [PMID: 37138868] [http://dx.doi.org/10.1016/j.genrep.2021.101298] [http://dx.doi.org/10.1016/j.ebiom.2016.04.030] [PMID: 27428420] [http://dx.doi.org/10.1007/s10815-019-01687-4] [PMID: 31938932] [http://dx.doi.org/10.3892/mmr.2024.13167] [PMID: 38240108] [http://dx.doi.org/10.1016/j.jri.2021.103340] [PMID: 34139652] [http://dx.doi.org/10.18240/ijo.2024.07.07] [PMID: 39026907] [http://dx.doi.org/10.1080/09513590.2017.1409717] [PMID: 29308924] [http://dx.doi.org/10.1038/cddis.2014.414] [PMID: 25275597] [http://dx.doi.org/10.1038/cddis.2017.95] [PMID: 28300844] [http://dx.doi.org/10.3389/fimmu.2019.00003] [PMID: 30713533] [http://dx.doi.org/10.1093/humrep/deac248] [PMID: 36413036] [http://dx.doi.org/10.1002/path.5339] [PMID: 31418859] [http://dx.doi.org/10.25122/jml-2020-0117] [PMID: 33072202] [http://dx.doi.org/10.1016/j.pupt.2012.02.006] [PMID: 22724137] [http://dx.doi.org/10.1186/s13018-020-1553-7] [PMID: 32054483] [http://dx.doi.org/10.3389/fimmu.2020.610963] [PMID: 33381124] [http://dx.doi.org/10.1016/j.jdermsci.2017.12.008] [PMID: 29279286] [http://dx.doi.org/10.1124/mol.107.042176] [PMID: 18252806] [http://dx.doi.org/10.1016/j.fertnstert.2007.12.067] [PMID: 18314120] [http://dx.doi.org/10.1186/s12905-021-01560-6] [PMID: 34930225] [http://dx.doi.org/10.3109/s10165-009-0175-z] [PMID: 19458908] [http://dx.doi.org/10.18632/aging.205034] [PMID: 37724890] [PMID: 39306730] [http://dx.doi.org/10.2174/1566524023666220819122948] [PMID: 35986537] [http://dx.doi.org/10.1016/j.fertnstert.2005.08.017] [PMID: 16595205] [http://dx.doi.org/10.5301/JE.2012.9070] [http://dx.doi.org/10.21873/invivo.11970] [PMID: 32606145] [PMCID: PMC7439897] [http://dx.doi.org/10.1210/en.2008-0352] [PMID: 18703630] [http://dx.doi.org/10.2147/OTT.S493643] [PMID: 39989503] [PMID: 35875336] [http://dx.doi.org/10.1093/humupd/dmx016] [PMID: 28903471] [http://dx.doi.org/10.1165/rcmb.2004-0288OC] [PMID: 15653932] [http://dx.doi.org/10.1111/j.1582-4934.2008.00647.x] [PMID: 20141610] [http://dx.doi.org/10.1016/j.yexmp.2020.104468] [PMID: 32445750] [http://dx.doi.org/10.1530/REP-19-0597] [PMID: 32155128] [http://dx.doi.org/10.3389/fonc.2018.00592] [PMID: 30581772]

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-08-20T06:14:21.026120+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-08-20T06:10:16.490565+00:00
unpaywall
last seen: 2026-08-20T06:30:07.000247+00:00
License: CC0 · commercial use OK