Research Article
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Year 2025, Volume: 26 Issue: 2, 213 - 222, 15.10.2025

Ayşegül Yılmaz , Demet Kaçaroğlu

Abstract

Mezenkimal kök hücreler (MSC’ler), doku onarımı, bağışıklık desteği ve kanser karşıtı tedaviler açısından kritik öneme sahip progenitör hücrelerdir. Farklı dokulardan izole edilen MSC’lerin göç, immünomodülasyon ve rejenerasyon gibi fonksiyonları Toll-benzeri reseptörler (TLR’ler) aracılığıyla düzenlenmektedir. Özellikle, TLR3 aktivasyonu MSC’lerin immünosupresif ve terapötik özelliklerini artırmaktadır. Bu çalışmada, TLR3 uyarımının insan göbek kordonu kaynaklı MSC’lerin (UK-MSC’ler) canlılığı, fenotip ile ilişkili gen ekspresyonu üzerindeki etkileri ile bu hücrelerin Panc-1 pankreas kanseri hücreleriyle ortak kültürdeki etkileri araştırılmıştır. UK-MSC’ler kültür ortamında çoğaltıldı ve mezenkimal yüzey belirteçleri açısından akım sitometrisi ile karakterize edildi. TLR3 sinyali, Poly(A:U) agonisti ve CU-CPT4a antagonisti ile modüle edildi. Hücre canlılığı 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolyum bromür testi ile değerlendirildi ve gen ekspresyonu gliseraldehit- 3-fosfat dehidrogenaz referans geni kullanılarak kantitatif gerçek zamanlı ters transkripsiyon polimeraz zincir reaksiyonu ile ölçüldü. Panc-1 pankreas kanseri hücreleri UK-MSC’lerle ko-kültüre edilerek TLR3 aracılı etkiler analiz edildi. Tüm veriler ortalama ± ortalamanın standart hatası olarak sunuldu ve istatistiksel analiz varyans analizi veya t-test ile yapıldı (p ≤ 0,05). TLR3 agonistlerinin hücre canlılığını artırdığı, TLR3 antagonistlerinin ise azalttığı gözlemlenmiştir. Ayrıca, hem agonist hem de antagonistlerin CD44, CDH1 ve VIM genlerinin ekspresyonunu düzenlediği bulunmuştur. UK-MSC ve Panc-1 hücreleri 10:1 oranında ortak kültüre alındığında, TLR3 aktivasyonu ve inhibisyonunun CD44, CDH1, CLDN1, VIM, ZEB1, MMP9, MMP2, TIMP1, VEGFR2 ve PLAU gibi MSC ile ilişkili genlerin ekspresyon profillerini etkilediği gösterilmiştir. Sonuç olarak, TLR3 sinyal iletiminin UK-MSC’lerin canlılığını, mezenkimal fenotipin korunmasını ve Panc-1 kanser hücrelerine yanıtla ilişkili fenotipini etkilediği gözlemlenmiştir. Bu bulgular, TLR3 sinyal iletiminin UK-MSC fonksiyonlarını modüle etmedeki önemini vurgulamakta ve özellikle tümörle ilişkili uygulamalarda MSC tabanlı tedavi stratejilerini geliştirmede potansiyel bir araç olabileceğini düşündürmektedir. Bu çalışmanın, TLR3 sinyal iletiminin UK-MSC’lerin biyolojik işlevleri üzerindeki etkilerini aydınlatmaya yardımcı olacağına ve gelecekteki araştırmalara temel oluşturacağına inanmaktayız.

Project Number

124S740

References

  • Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001). Recognition of double-stranded RNA and activation of NF-κB by toll-like receptor 3. Nature, 413(6857), 732–738. https://doi.org/10.1038/35099560
  • Bhat, A. A., Syed, N., Therachiyil, L., Nisar, S., Hashem, S., Macha, M. A., Yadav, S. K., Krishnankutty, R., Muralitharan, S., Al-Naemi, H., Bagga, P., Reddy, R., Dhawan, P., Akobeng, A., Uddin, S., Frenneaux, M. P., El-Rifai, W., & Haris, M. (2020). Claudin-1, a double-edged sword in cancer. International Journal of Molecular Sciences, 21(2), 569. https://doi.org/10.3390/ijms21020569
  • Bhat, A. A., Uppada, S., Achkar, I. W., Hashem, S., Yadav, S. K., Shanmugakonar, M., Al-Naemi, H. A., Haris, M., & Uddin, S. (2019). Tight junction proteins and signaling pathways in cancer and inflammation: A functional crosstalk. Frontiers in Physiology, 10, 1942. https://doi.org/10.3389/fphys.2018.01942
  • Viswanathan, S., Wahab, M. R. A., Baskar, G., Natarajan, S., & Ranjan, K. (2023). Implications of toll-like receptors (TLRs) and their signaling mechanisms in human cancers. Pathology, Research and Practice, 248, 154673. https://doi. org/10.1016/j.prp.2023.154673
  • Chen, X., Zhang, Z. Y., Zhou, H., & Zhou, G. W. (2014). Characterization of mesenchymal stem cells under the stimulation of toll-like receptor agonists. Development, Growth & Differentiation, 56(3), 233–244. https://doi.org/10.1111/ dgd.12124
  • Chulpanova, D. S., Kitaeva, K. V., Tazetdinova, L. G., James, V., Rizvanov, A. A., & Solovyeva, V. V. (2018). Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Frontiers in Pharmacology, 9, 259. https://doi.org/10.3389/fphar.2018.00259
  • El Omar, R., Beroud, J., Stoltz, J. F., Menu, P., Velot, E., & Decot, V. (2014). Umbilical cord mesenchymal stem cells: The new gold standard for mesenchymal stem cell-based therapies? Tissue Engineering Part B: Reviews, 20(6), 523–544. https://doi.org/10.1089/ten.TEB.2013.0664
  • Eskandari, F., Zolfaghari, S., Yazdanpanah, A., Shabestari, R. M., Fomeshi, M. R., Milan, P. B., Kiani, J., Zomorrod, M. S., & Safa, M. (2023). TLR3 stimulation improves the migratory potency of adipose-derived mesenchymal stem cells through the stress response pathway in the melanoma mouse model. Molecular Biology Reports, 50(3), 2293–2304. https://doi.org/10.1007/s11033-022-08111-8
  • Fayyad-Kazan, M., Fayyad-Kazan, H., Lagneaux, L., & Najar, M. (2016). The potential of mesenchymal stromal cells in immunotherapy. Immunotherapy, 8(7), 839–842. https://doi.org/10.2217/imt-2016-0037
  • Gholizadeh-Ghaleh Aziz, S., Alipour, S., Ranjbarvan, P., Azari, A., Babaei, G., & Golchin, A. (2021). Critical roles of TLRs on the polarization of mesenchymal stem cells for cell therapy of viral infections: A notice for COVID-19 treatment. Comparative Clinical Pathology, 30(1), 119–128. https://doi.org/10.1007/ s00580-021-03209-0
  • Golchin, A., Seyedjafari, E., & Ardeshirylajimi, A. (2020). Mesenchymal stem cell therapy for COVID-19: Present or future. Stem Cell Reviews and Reports, 16(3), 427–433. https://doi.org/10.1007/s12015-020-09973-w
  • Hmadcha, A., Martin-Montalvo, A., Gauthier, B. R., Soria, B., & Capilla- Gonzalez, V. (2020). Therapeutic potential of mesenchymal stem cells for cancer therapy. Frontiers in Bioengineering and Biotechnology, 8, 43. https://doi. org/10.3389/fbioe.2020.00043
  • Huang, Y., & Chen, Z. (2016). Inflammatory bowel disease related innate immunity and adaptive immunity. American Journal of Translational Research, 8(6), 2490–2497.
  • Hwang, S., Sung, D. K., Kim, Y. E., Yang, M., Ahn, S. Y., Sung, S. I., & Chang, Y. S. (2023). Mesenchymal stromal cells primed by toll-like receptors 3 and 4 enhanced anti-inflammatory effects against LPS-induced macrophages via extracellular vesicles. International Journal of Molecular Sciences, 24(22), 16264. https://doi.org/10.3390/ijms242216264
  • Huerta, C. T., Voza, F. A., Ortiz, Y. Y., Liu, Z. J., & Velazquez, O. C. (2023). Mesenchymal stem cell-based therapy for non-healing wounds due to chronic limb-threatening ischemia: A review of preclinical and clinical studies. Frontiers in Cardiovascular Medicine, 10, 1113982. https://doi.org/10.3389/ fcvm.2023.1113982
  • Ishihara, S., Rumi, M. A., Ortega-Cava, C. F., Kazumori, H., Kadowaki, Y., Ishimura, N., & Kinoshita, Y. (2006). Therapeutic targeting of toll-like receptors in gastrointestinal inflammation. Current Pharmaceutical Design, 12(33), 4215– 4228. https://doi.org/10.2174/138161206778743448
  • Liu, X., Zhou, Z., Zeng, W. N., Zeng, Q., & Zhang, X. (2023). The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology. Frontiers in Cell and Developmental Biology, 11, 1277686. https://doi.org/10.3389/fcell.2023.1277686
  • Monguió-Tortajada, M., Bayes-Genis, A., Rosell, A., & Roura, S. (2021). Are mesenchymal stem cells and derived extracellular vesicles valuable to halt the COVID-19 inflammatory cascade? Current evidence and future perspectives. Thorax, 76(2), 196–200. https://doi.org/10.1136/thoraxjnl-2020-215717
  • Najar, M., Fayyad-Kazan, M., Merimi, M., Burny, A., Bron, D., Fayyad-Kazan, H., Meuleman, N., & Lagneaux, L. (2019). Mesenchymal stromal cells and natural killer cells: A complex story of love and hate. Current Stem Cell Research & Therapy, 14(1), 14–21. https://doi.org/10.2174/1574888X13666180912125736
  • Najar, M., Krayem, M., Meuleman, N., Bron, D., & Lagneaux, L. (2017). Mesenchymal stromal cells and toll-like receptor priming: A critical review. Immune Network, 17(2), 89–102. https://doi.org/10.4110/in.2017.17.2.89
  • Nwabo Kamdje, A. H., Seke Etet, P. F., Simo Tagne, R., Vecchio, L., Lukong, K. E., & Krampera, M. (2020). Tumor microenvironment uses a reversible reprogramming of mesenchymal stromal cells to mediate pro-tumorigenic effects. Frontiers in Cell and Developmental Biology, 8, 545126. https://doi.org/10.3389/ fcell.2020.545126
  • Raicevic, G., Najar, M., Stamatopoulos, B., De Bruyn, C., Meuleman, N., Bron, D., Toungouz, M., & Lagneaux, L. (2011). The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties. Cellular Immunology, 270(2), 207–216. https://doi.org/10.1016/j. cellimm.2011.05.010
  • Salaun, B., Coste, I., Rissoan, M.-C., Lebecque, S. J., & Renno, T. (2006). TLR3 can directly trigger apoptosis in human cancer cells. Journal of Immunology, 176(8), 4894–4901. https://doi.org/10.4049/jimmunol.176.8.4894
  • Tolstova, T., Dotsenko, E., Kozhin, P., Novikova, S., Zgoda, V., Rusanov, A., & Luzgina, N. (2023). The effect of TLR3 priming conditions on MSC immunosuppressive properties. Stem Cell Research & Therapy, 14, 344. https:// doi.org/10.1186/s13287-023-03579-y
  • Tomchuck, S. L., Zwezdaryk, K. J., Coffelt, S. B., Waterman, R. S., Danka, E. S., & Scandurro, A. B. (2008). Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells, 26(1), 99–107. https://doi.org/10.1634/stemcells.2007-0563
  • Waterman, R. S., Tomchuck, S. L., Henkle, S. L., & Betancourt, A. M. (2010). A new mesenchymal stem cell (MSC) paradigm: Polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One, 5(4), e10088. https://doi.org/10.1371/journal.pone.0010088
  • Yamamoto-Furusho, J. K., & Podolsky, D. K. (2007). Innate immunity in inflammatory bowel disease. World Journal of Gastroenterology, 13(42), 5577– 5580. https://doi.org/10.3748/wjg.v13.i42.5577
  • Zhang, H., Jin, C., Hua, J., Chen, Z., Gao, W., Xu, W., Zhou, L., & Shan, L. (2024). Roles of microenvironment on mesenchymal stem cells therapy for osteoarthritis. Journal of Inflammation Research, 17, 7069–7079. https://doi. org/10.2147/JIR.S475617
  • Zhao, C., Zhang, L., Kong, W., Liang, J., Xu, X., Wu, H., Feng, X., Hua, B., Wang, H., & Sun, L. (2015). Umbilical cord-derived mesenchymal stem cells inhibit cadherin-11 expression by fibroblast-like synoviocytes in rheumatoid arthritis. Journal of Immunology Research, 2015, 137695. https://doi. org/10.1155/2015/137695
  • Zheng, R., & Ma, J. (2022). Immunotherapeutic implications of toll-like receptors activation in tumor microenvironment. Pharmaceutics, 14(11), 2285. https://doi. org/10.3390/pharmaceutics14112285

Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture

Year 2025, Volume: 26 Issue: 2, 213 - 222, 15.10.2025

Ayşegül Yılmaz , Demet Kaçaroğlu

Abstract

Mesenchymal stem cells (MSCs) are progenitor cells isolated from various tissues and are crucial for tissue repair, immune support, and anticancer therapies. MSC functions such as migration, immunomodulation, and regeneration are regulated through Toll-like receptors (TLRs). In particular, TLR3 activation enhances the immunosuppressive and therapeutic capabilities of MSCs. This research employed human umbilical cord-derived MSCs (UCMSCs) and investigated the effects of TLR3 stimulation on their viability, phenotype-associated gene expression, and during co-culture with Panc-1 pancreatic cancer cells. UCMSCs were cultured and characterized for mesenchymal markers by flow cytometry. TLR3- based signaling was modulated using Poly(A:U) (an agonist) and CU-CPT4a (an antagonist). Cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, and relative gene expression was measured employing quantitative reverse transcription polymerase chain reaction. Panc-1 cells were co-cultured with UCMSCs to evaluate TLR3-mediated effects. Data are presented as the means ± standard error of the mean, with statistical significance determined by analysis of variance (p ≤ 0.05). The TLR3 agonist improved cell viability, whereas the antagonist reduced it. Additionally, both regulated the expression of CD44, CDH1, and VIMs. When UCMSCs and Panc-1 cells were cocultured at 10:1, TLR3 affected the expression of MSC-related genes, including CD44, CDH1, CLDN1, VIM, ZEB1, MMP9, MMP2, TIMP1, VEGFR2, and PLAU. Thus, TLR3-based signaling influenced the viability, maintenance of the mesenchymal phenotype, and Panc-1 coculture-associated phenotype in UCMSCs. These results underscore the crucial role of TLR3-based signaling in modulating UCMSC function and suggest its potential utility in enhancing MSC-based therapeutic strategies. We believe that these results can help elucidate the role of TLR3-based signaling on UCMSC functions and provide a basis for future research.

Keywords

Mesenchymal stem cell TLR3 UCMSC pancreatic ductal adenocarcinoma cancer biology

Ethical Statement

Since the article does not contain any studies with human or animal subject, its approval to the ethics committee was not required.

Supporting Institution

TÜBİTAK

Project Number

124S740

References

  • Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001). Recognition of double-stranded RNA and activation of NF-κB by toll-like receptor 3. Nature, 413(6857), 732–738. https://doi.org/10.1038/35099560
  • Bhat, A. A., Syed, N., Therachiyil, L., Nisar, S., Hashem, S., Macha, M. A., Yadav, S. K., Krishnankutty, R., Muralitharan, S., Al-Naemi, H., Bagga, P., Reddy, R., Dhawan, P., Akobeng, A., Uddin, S., Frenneaux, M. P., El-Rifai, W., & Haris, M. (2020). Claudin-1, a double-edged sword in cancer. International Journal of Molecular Sciences, 21(2), 569. https://doi.org/10.3390/ijms21020569
  • Bhat, A. A., Uppada, S., Achkar, I. W., Hashem, S., Yadav, S. K., Shanmugakonar, M., Al-Naemi, H. A., Haris, M., & Uddin, S. (2019). Tight junction proteins and signaling pathways in cancer and inflammation: A functional crosstalk. Frontiers in Physiology, 10, 1942. https://doi.org/10.3389/fphys.2018.01942
  • Viswanathan, S., Wahab, M. R. A., Baskar, G., Natarajan, S., & Ranjan, K. (2023). Implications of toll-like receptors (TLRs) and their signaling mechanisms in human cancers. Pathology, Research and Practice, 248, 154673. https://doi. org/10.1016/j.prp.2023.154673
  • Chen, X., Zhang, Z. Y., Zhou, H., & Zhou, G. W. (2014). Characterization of mesenchymal stem cells under the stimulation of toll-like receptor agonists. Development, Growth & Differentiation, 56(3), 233–244. https://doi.org/10.1111/ dgd.12124
  • Chulpanova, D. S., Kitaeva, K. V., Tazetdinova, L. G., James, V., Rizvanov, A. A., & Solovyeva, V. V. (2018). Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Frontiers in Pharmacology, 9, 259. https://doi.org/10.3389/fphar.2018.00259
  • El Omar, R., Beroud, J., Stoltz, J. F., Menu, P., Velot, E., & Decot, V. (2014). Umbilical cord mesenchymal stem cells: The new gold standard for mesenchymal stem cell-based therapies? Tissue Engineering Part B: Reviews, 20(6), 523–544. https://doi.org/10.1089/ten.TEB.2013.0664
  • Eskandari, F., Zolfaghari, S., Yazdanpanah, A., Shabestari, R. M., Fomeshi, M. R., Milan, P. B., Kiani, J., Zomorrod, M. S., & Safa, M. (2023). TLR3 stimulation improves the migratory potency of adipose-derived mesenchymal stem cells through the stress response pathway in the melanoma mouse model. Molecular Biology Reports, 50(3), 2293–2304. https://doi.org/10.1007/s11033-022-08111-8
  • Fayyad-Kazan, M., Fayyad-Kazan, H., Lagneaux, L., & Najar, M. (2016). The potential of mesenchymal stromal cells in immunotherapy. Immunotherapy, 8(7), 839–842. https://doi.org/10.2217/imt-2016-0037
  • Gholizadeh-Ghaleh Aziz, S., Alipour, S., Ranjbarvan, P., Azari, A., Babaei, G., & Golchin, A. (2021). Critical roles of TLRs on the polarization of mesenchymal stem cells for cell therapy of viral infections: A notice for COVID-19 treatment. Comparative Clinical Pathology, 30(1), 119–128. https://doi.org/10.1007/ s00580-021-03209-0
  • Golchin, A., Seyedjafari, E., & Ardeshirylajimi, A. (2020). Mesenchymal stem cell therapy for COVID-19: Present or future. Stem Cell Reviews and Reports, 16(3), 427–433. https://doi.org/10.1007/s12015-020-09973-w
  • Hmadcha, A., Martin-Montalvo, A., Gauthier, B. R., Soria, B., & Capilla- Gonzalez, V. (2020). Therapeutic potential of mesenchymal stem cells for cancer therapy. Frontiers in Bioengineering and Biotechnology, 8, 43. https://doi. org/10.3389/fbioe.2020.00043
  • Huang, Y., & Chen, Z. (2016). Inflammatory bowel disease related innate immunity and adaptive immunity. American Journal of Translational Research, 8(6), 2490–2497.
  • Hwang, S., Sung, D. K., Kim, Y. E., Yang, M., Ahn, S. Y., Sung, S. I., & Chang, Y. S. (2023). Mesenchymal stromal cells primed by toll-like receptors 3 and 4 enhanced anti-inflammatory effects against LPS-induced macrophages via extracellular vesicles. International Journal of Molecular Sciences, 24(22), 16264. https://doi.org/10.3390/ijms242216264
  • Huerta, C. T., Voza, F. A., Ortiz, Y. Y., Liu, Z. J., & Velazquez, O. C. (2023). Mesenchymal stem cell-based therapy for non-healing wounds due to chronic limb-threatening ischemia: A review of preclinical and clinical studies. Frontiers in Cardiovascular Medicine, 10, 1113982. https://doi.org/10.3389/ fcvm.2023.1113982
  • Ishihara, S., Rumi, M. A., Ortega-Cava, C. F., Kazumori, H., Kadowaki, Y., Ishimura, N., & Kinoshita, Y. (2006). Therapeutic targeting of toll-like receptors in gastrointestinal inflammation. Current Pharmaceutical Design, 12(33), 4215– 4228. https://doi.org/10.2174/138161206778743448
  • Liu, X., Zhou, Z., Zeng, W. N., Zeng, Q., & Zhang, X. (2023). The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology. Frontiers in Cell and Developmental Biology, 11, 1277686. https://doi.org/10.3389/fcell.2023.1277686
  • Monguió-Tortajada, M., Bayes-Genis, A., Rosell, A., & Roura, S. (2021). Are mesenchymal stem cells and derived extracellular vesicles valuable to halt the COVID-19 inflammatory cascade? Current evidence and future perspectives. Thorax, 76(2), 196–200. https://doi.org/10.1136/thoraxjnl-2020-215717
  • Najar, M., Fayyad-Kazan, M., Merimi, M., Burny, A., Bron, D., Fayyad-Kazan, H., Meuleman, N., & Lagneaux, L. (2019). Mesenchymal stromal cells and natural killer cells: A complex story of love and hate. Current Stem Cell Research & Therapy, 14(1), 14–21. https://doi.org/10.2174/1574888X13666180912125736
  • Najar, M., Krayem, M., Meuleman, N., Bron, D., & Lagneaux, L. (2017). Mesenchymal stromal cells and toll-like receptor priming: A critical review. Immune Network, 17(2), 89–102. https://doi.org/10.4110/in.2017.17.2.89
  • Nwabo Kamdje, A. H., Seke Etet, P. F., Simo Tagne, R., Vecchio, L., Lukong, K. E., & Krampera, M. (2020). Tumor microenvironment uses a reversible reprogramming of mesenchymal stromal cells to mediate pro-tumorigenic effects. Frontiers in Cell and Developmental Biology, 8, 545126. https://doi.org/10.3389/ fcell.2020.545126
  • Raicevic, G., Najar, M., Stamatopoulos, B., De Bruyn, C., Meuleman, N., Bron, D., Toungouz, M., & Lagneaux, L. (2011). The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties. Cellular Immunology, 270(2), 207–216. https://doi.org/10.1016/j. cellimm.2011.05.010
  • Salaun, B., Coste, I., Rissoan, M.-C., Lebecque, S. J., & Renno, T. (2006). TLR3 can directly trigger apoptosis in human cancer cells. Journal of Immunology, 176(8), 4894–4901. https://doi.org/10.4049/jimmunol.176.8.4894
  • Tolstova, T., Dotsenko, E., Kozhin, P., Novikova, S., Zgoda, V., Rusanov, A., & Luzgina, N. (2023). The effect of TLR3 priming conditions on MSC immunosuppressive properties. Stem Cell Research & Therapy, 14, 344. https:// doi.org/10.1186/s13287-023-03579-y
  • Tomchuck, S. L., Zwezdaryk, K. J., Coffelt, S. B., Waterman, R. S., Danka, E. S., & Scandurro, A. B. (2008). Toll-like receptors on human mesenchymal stem cells drive their migration and immunomodulating responses. Stem Cells, 26(1), 99–107. https://doi.org/10.1634/stemcells.2007-0563
  • Waterman, R. S., Tomchuck, S. L., Henkle, S. L., & Betancourt, A. M. (2010). A new mesenchymal stem cell (MSC) paradigm: Polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One, 5(4), e10088. https://doi.org/10.1371/journal.pone.0010088
  • Yamamoto-Furusho, J. K., & Podolsky, D. K. (2007). Innate immunity in inflammatory bowel disease. World Journal of Gastroenterology, 13(42), 5577– 5580. https://doi.org/10.3748/wjg.v13.i42.5577
  • Zhang, H., Jin, C., Hua, J., Chen, Z., Gao, W., Xu, W., Zhou, L., & Shan, L. (2024). Roles of microenvironment on mesenchymal stem cells therapy for osteoarthritis. Journal of Inflammation Research, 17, 7069–7079. https://doi. org/10.2147/JIR.S475617
  • Zhao, C., Zhang, L., Kong, W., Liang, J., Xu, X., Wu, H., Feng, X., Hua, B., Wang, H., & Sun, L. (2015). Umbilical cord-derived mesenchymal stem cells inhibit cadherin-11 expression by fibroblast-like synoviocytes in rheumatoid arthritis. Journal of Immunology Research, 2015, 137695. https://doi. org/10.1155/2015/137695
  • Zheng, R., & Ma, J. (2022). Immunotherapeutic implications of toll-like receptors activation in tumor microenvironment. Pharmaceutics, 14(11), 2285. https://doi. org/10.3390/pharmaceutics14112285
There are 30 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other), Genetic Immunology
Journal Section Research Article/Araştırma Makalesi
Authors

Ayşegül Yılmaz 0000-0002-9541-9853

Demet Kaçaroğlu 0000-0003-4920-0516

Project Number 124S740
Early Pub Date October 6, 2025
Publication Date October 15, 2025
Submission Date May 31, 2025
Acceptance Date September 17, 2025
Published in Issue Year 2025 Volume: 26 Issue: 2

Cite

APA Yılmaz, A., & Kaçaroğlu, D. (2025). Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture. Trakya University Journal of Natural Sciences, 26(2), 213-222.
AMA Yılmaz A, Kaçaroğlu D. Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture. Trakya Univ J Nat Sci. October 2025;26(2):213-222.
Chicago Yılmaz, Ayşegül, and Demet Kaçaroğlu. “Toll-Like Receptor 3-Mediated Modulation of Umbilical Cord Mesenchymal Stem Cell Phenotype and Pancreatic Cancer Cell Responses During Coculture”. Trakya University Journal of Natural Sciences 26, no. 2 (October 2025): 213-22.
EndNote Yılmaz A, Kaçaroğlu D (October 1, 2025) Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture. Trakya University Journal of Natural Sciences 26 2 213–222.
IEEE A. Yılmaz and D. Kaçaroğlu, “Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture”, Trakya Univ J Nat Sci, vol. 26, no. 2, pp. 213–222, 2025.
ISNAD Yılmaz, Ayşegül - Kaçaroğlu, Demet. “Toll-Like Receptor 3-Mediated Modulation of Umbilical Cord Mesenchymal Stem Cell Phenotype and Pancreatic Cancer Cell Responses During Coculture”. Trakya University Journal of Natural Sciences 26/2 (October2025), 213-222.
JAMA Yılmaz A, Kaçaroğlu D. Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture. Trakya Univ J Nat Sci. 2025;26:213–222.
MLA Yılmaz, Ayşegül and Demet Kaçaroğlu. “Toll-Like Receptor 3-Mediated Modulation of Umbilical Cord Mesenchymal Stem Cell Phenotype and Pancreatic Cancer Cell Responses During Coculture”. Trakya University Journal of Natural Sciences, vol. 26, no. 2, 2025, pp. 213-22.
Vancouver Yılmaz A, Kaçaroğlu D. Toll-like receptor 3-mediated modulation of umbilical cord mesenchymal stem cell phenotype and pancreatic cancer cell responses during coculture. Trakya Univ J Nat Sci. 2025;26(2):213-22.

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