Araştırma Makalesi
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Wharton Jölesi Kökenli Mezenkimal Kök Hücrelerden Elde Edilen Eksozomların Akciğer, Pankreas ve Karaciğer Kanseri Hücrelerinin Canlılığı ve Metabolik Aktivitesi Üzerindeki Etkilerinin Araştırılması

Yıl 2025, Sayı: 27, 824 - 836, 31.12.2025
https://doi.org/10.38079/igusabder.1534054

Öz

Amaç: Mezenkimal kök hücreler (MKH) sitokinler, kemokinler, eksozomlar salgılayarak veya doğrudan temas yoluyla aynı mikroçevredeki kanser hücreleri üzerinde etki gösterir. WJ-MKH kökenli eksozomların akciğer, pankreas ve karaciğer kanseri hücre hatlarının canlılığı ve metabolik aktivitesi üzerindeki etkileri incelenmesi amaçlanmıştır.
Yöntem: Bu çalışmada Wharton Jölesi (WJ)-MKH kökenli eksozomlar A549, Panc-1 ve HepG2 hücrelerine 1-5-10-15 ve 20 milyon partikül eksozom olarak uygulandı. Canlılık üzerindeki etkiler 48 ve 96. saatlerde MTT analizi ile değerlendirilmiştir. Metabolik aktivitesi üzerindeki etkiler 96. saatin sonunda kalsein boyaması ile floresan yoğunluğu ile değerlendirilmiştir. Hücre metabolik aktivitesi floresan yoğunluğu kullanılarak hesaplanmıştır.
Bulgular: Kontrol grubunda 96. saatin sonunda A549 hücrelerinde % 62, Panc-1 hücrelerinde %95 ve HepG2 hücrelerinde %67 artış gözlemlenirken 20 milyon eksozom uygulanan grupta ise A549 hücrelerinde %36, Panc-1 hücrelerinde %43 ve HepG2 hücrelerinde %31 artış gözlenmiştir. Proliferasyon oranı 20 milyon eksozom uygulanan grupta kontrol grubuna göre (% 100) A549: %61, Panc-1: %64 ve HepG2: %68 olarak hesaplanmıştır. Ön bulgular, WJ-MSC kökenli eksozomların kanser hücrelerine uygulandığında kanser hücrelerinin canlılığını ve metabolik aktivitesini artırmadığını ve zaman-konsantrasyona bağlı olarak azalabildiği de gösterilmiştir.
Sonuç: WJ-MKH türevi eksozomlar, yüksek stroma içeriğine sahip tümörlerde in vitro hücre canlılığı ve metabolik aktivite üzerinde etkili olabilir ve tümör hücreleri üzerindeki diğer mekanizmalar üzerindeki etkilerinin araştırılması gerekmektedir.

Kaynakça

  • 1. Pountos I, Giannoudis PV. Biology of mesenchymal stem cells. Injury. 2005;36 Suppl 3:S8-S12.
  • 2. Carr RM, Fernandez-Zapico ME. Pancreatic cancer microenvironment, to target or not to target? EMBO Mol Med. 2016;8(2):80-82.
  • 3. Rahmatizadeh F, Gholizadeh-Ghaleh Aziz S, Khodadadi K, et al. Bidirectional and opposite effects of naïve mesenchymal stem cells on tumor growth and progression. Adv Pharm Bull. 2019;9(4):539-558.
  • 4. Pawitan JA, Bui TA, Mubarok W, et al. Enhancement of the therapeutic capacity of mesenchymal stem cells by genetic modification: a systematic review. Front Cell Dev Biol. 2020;8:587776.
  • 5. Lin Z, Wu Y, Xu Y, Li G, Li Z, Liu T. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Mol Cancer. 2022;21(1):179.
  • 6. Shojaei S, Hashemi SM, Ghanbarian H, Salehi M, Mohammadi-Yeganeh S. Effect of mesenchymal stem cells-derived exosomes on tumor microenvironment: Tumor progression versus tumor suppression. J Cell Physiol. 2019;234(4):3394-3409.
  • 7. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019;18(1):75.
  • 8. Zhou J, Tan X, Tan Y, Li Q, Ma J, Wang G. Mesenchymal stem cell derived exosomes in cancer progression, metastasis and drug delivery: a comprehensive review. J Cancer. 2018;9(17):3129-3137.
  • 9. Wu S, Ju GQ, Du T, Zhu YJ, Liu GH. Microvesicles derived from human umbilical cord Wharton's jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo. PLoS One. 2013;8(4):e61366.
  • 10. Pascucci L, Coccè V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release. 2014;192:262-270.
  • 11. Vakhshiteh F, Atyabi F, Ostad SN. Mesenchymal stem cell exosomes: a two-edged sword in cancer therapy. Int J Nanomedicine. 2019;14:2847-2859.
  • 12. Christodoulou I, Goulielmaki M, Devetzi M, Panagiotidis M, Koliakos G, Zoumpourlis V. Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review. Stem Cell Res Ther. 2018;9(1):336.
  • 13. Gu H, Ji R, Zhang X, et al. Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway. Mol Med Rep. 2016;14(4):3452–3458.
  • 14. Zhu W, Huang L, Li Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28–37.
  • 15. Roccaro AM, Sacco A, Maiso P, et al. Bone marrow mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest. 2013;123(4):1542–1555.
  • 16. Qi J, Zhou Y, Jiao Z, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth through Hedgehog signaling pathway. Cell Physiol Biochem. 2017;42(6):2242–2254.
  • 17. Gao G, Wang L, Li C. Circ_0006790 carried by bone marrow mesenchymal stem cell-derived exosomes regulates S100A11 DNA methylation through binding to CBX7 in pancreatic ductal adenocarcinoma. Am J Cancer Res. 2022;12(5):1934–1959.
  • 18. Xu Y, Shen L, Li F, Yang J, Wan X, Ouyang M. microRNA-16-5p-containing exosomes derived from bone marrow-derived mesenchymal stem cells inhibit proliferation, migration, and invasion, while promoting apoptosis of colorectal cancer cells by downregulating ITGA2. J Cell Physiol. 2019;234(11):21380–21394.
  • 19. Xu Y, Liu N, Wei Y, et al. Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells. Aging (Albany NY). 2020;12(19):19660–19676.
  • 20. Wang B, Xu Y, Wei Y, et al. Human mesenchymal stem cell-derived exosomal microRNA-143 promotes apoptosis and suppresses cell growth in pancreatic cancer via target gene regulation. Front Genet. 2021;12:581694.
  • 21. Kacaroglu D, Gurbuz N. Comparison of therapeutic potential of macrophage- or mesenchymal stem cell-derived exosomes in pancreatic cancer: An updated review. World J Stem Cells. 2025;17(8):107400.
  • 22. Ünal Halbutoğulları ZS, Utkan Korun ZE, Subaşı Demir C, Kılıç KC, Alper B, Yazır Y. Optimization of protein quantification in wharton jelly-derived mesenchymal stem cell exosomes. Acta Med Nicomedia. 2023;6(3):452-458.
  • 23. Ghasempour E, Hesami S, Movahed E, Keshel SH, Doroudian M. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy in the brain tumors. Stem Cell Res Ther. 2022;13(1):527.
  • 24. Liu Y, Song B, Wei Y, et al. Exosomes from mesenchymal stromal cells enhance imatinib-induced apoptosis in human leukemia cells via activation of caspase signaling pathway. Cytotherapy. 2018;20(2):181-188.
  • 25. Takahara K, Ii M, Inamoto T, et al. MicroRNA-145 mediates the inhibitory effect of adipose tissue-derived stromal cells on prostate cancer. Stem Cells Dev. 2016;25(17):1290-1298.
  • 26. Karaoz E, Sun E, Demir CS. Mesenchymal stem cell-derived exosomes do not promote the proliferation of cancer cells in vitro. Int J Physiol Pathophysiol Pharmacol. 2019;11(4):177-189.
  • 27. Rezaeian A, Khatami F, Heidari Keshel S, et al. The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines. Sci Rep. 2022;12(1):20924.
  • 28. Ding Y, Cao F, Sun H, et al. Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression. Cancer Lett. 2019;442:351-361.
  • 29. Shang S, Wang J, Chen S, et al. Exosomal miRNA-1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer. Cancer Med. 2019;8(18):7728-7740.
  • 30. Kumar D, Gupta D, Shankar S, Srivastava RK. Biomolecular characterization of exosomes released from cancer stem cells: Possible implications for biomarker and treatment of cancer. Oncotarget. 2015;6(5):3280-3291.
  • 31. Maia J, Caja S, Strano Moraes MC, Couto N, Costa-Silva B. Exosome-based cell-cell communication in the tumor microenvironment. Front Cell Dev Biol. 2018;6:18.
  • 32. Lin R, Wang S, Zhao RC. Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model. Mol Cell Biochem. 2013;383(1-2):13-20.
  • 33. Del Fattore A, Luciano R, Saracino R, et al. Differential effects of extracellular vesicles secreted by mesenchymal stem cells from different sources on glioblastoma cells. Expert Opin Biol Ther. 2015;15(4):495-504.
  • 34. Bruno S, Collino F, Deregibus MC, Grange C, Tetta C, Camussi G. Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth. Stem Cells Dev. 2014;23(24):3072.

Exploring the Effects of WJ-MSC-Derived Exosomes on the Viability and Metabolic Activity of Lung, Pancreatic and Liver Cancer Cells

Yıl 2025, Sayı: 27, 824 - 836, 31.12.2025
https://doi.org/10.38079/igusabder.1534054

Öz

Aim: Mesenchymal stem cells (MSCs) act on cancer cells in the same microenvironment by secreting cytokines, chemokines, exosomes, or by direct contact. The purpose of this study is to analyse the impact of WJ-MSC-derived exosomes on the viability and metabolic activity of lung, pancreatic, and liver cancer cells.
Method: In this study, Wharton's Jelly (WJ)-MSCs-derived exosomes were added to A549, Panc-1, and HepG2 cells as 1-5-10-15 and 20 million particle exosomes. The effects on viability were evaluated by MTT analysis at 48 and 96 hours. The effects on metabolic activity were evaluated by calcein staining at the end of the 96th hour. Cell metabolic activity was calculated using fluorescence intensity.
Results: At the end of the 96th hour, 62% increase in A549 cells, 95% increase in Panc-1 cells and 67% increase in HepG2 cells were detected in the control group. In the group which 20 million exosomes were applied, 36% increase in A549 cells, 43% increase in Panc-1 cells and 31% increase in HepG2 cells were observed. The fluorescence intensity of 20 million exosomes was calculated as: A549: 61%, Panc-1: 64% and HepG2: 68%. Preliminary findings indicate that WJ-MSC-derived exosomes do not increase the viability and metabolic activity of cancer cells when applied to them. It was also shown that the viability and metabolic activity can decrease depending on time and concentration.
Conclusion: WJ-MSC-derived exosomes may be effective on cell viability and metabolic activity in vitro in tumors with high stroma content, and their effects on other mechanisms on tumor cells need to be investigated.

Kaynakça

  • 1. Pountos I, Giannoudis PV. Biology of mesenchymal stem cells. Injury. 2005;36 Suppl 3:S8-S12.
  • 2. Carr RM, Fernandez-Zapico ME. Pancreatic cancer microenvironment, to target or not to target? EMBO Mol Med. 2016;8(2):80-82.
  • 3. Rahmatizadeh F, Gholizadeh-Ghaleh Aziz S, Khodadadi K, et al. Bidirectional and opposite effects of naïve mesenchymal stem cells on tumor growth and progression. Adv Pharm Bull. 2019;9(4):539-558.
  • 4. Pawitan JA, Bui TA, Mubarok W, et al. Enhancement of the therapeutic capacity of mesenchymal stem cells by genetic modification: a systematic review. Front Cell Dev Biol. 2020;8:587776.
  • 5. Lin Z, Wu Y, Xu Y, Li G, Li Z, Liu T. Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Mol Cancer. 2022;21(1):179.
  • 6. Shojaei S, Hashemi SM, Ghanbarian H, Salehi M, Mohammadi-Yeganeh S. Effect of mesenchymal stem cells-derived exosomes on tumor microenvironment: Tumor progression versus tumor suppression. J Cell Physiol. 2019;234(4):3394-3409.
  • 7. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol Cancer. 2019;18(1):75.
  • 8. Zhou J, Tan X, Tan Y, Li Q, Ma J, Wang G. Mesenchymal stem cell derived exosomes in cancer progression, metastasis and drug delivery: a comprehensive review. J Cancer. 2018;9(17):3129-3137.
  • 9. Wu S, Ju GQ, Du T, Zhu YJ, Liu GH. Microvesicles derived from human umbilical cord Wharton's jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo. PLoS One. 2013;8(4):e61366.
  • 10. Pascucci L, Coccè V, Bonomi A, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release. 2014;192:262-270.
  • 11. Vakhshiteh F, Atyabi F, Ostad SN. Mesenchymal stem cell exosomes: a two-edged sword in cancer therapy. Int J Nanomedicine. 2019;14:2847-2859.
  • 12. Christodoulou I, Goulielmaki M, Devetzi M, Panagiotidis M, Koliakos G, Zoumpourlis V. Mesenchymal stem cells in preclinical cancer cytotherapy: a systematic review. Stem Cell Res Ther. 2018;9(1):336.
  • 13. Gu H, Ji R, Zhang X, et al. Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway. Mol Med Rep. 2016;14(4):3452–3458.
  • 14. Zhu W, Huang L, Li Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012;315(1):28–37.
  • 15. Roccaro AM, Sacco A, Maiso P, et al. Bone marrow mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest. 2013;123(4):1542–1555.
  • 16. Qi J, Zhou Y, Jiao Z, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth through Hedgehog signaling pathway. Cell Physiol Biochem. 2017;42(6):2242–2254.
  • 17. Gao G, Wang L, Li C. Circ_0006790 carried by bone marrow mesenchymal stem cell-derived exosomes regulates S100A11 DNA methylation through binding to CBX7 in pancreatic ductal adenocarcinoma. Am J Cancer Res. 2022;12(5):1934–1959.
  • 18. Xu Y, Shen L, Li F, Yang J, Wan X, Ouyang M. microRNA-16-5p-containing exosomes derived from bone marrow-derived mesenchymal stem cells inhibit proliferation, migration, and invasion, while promoting apoptosis of colorectal cancer cells by downregulating ITGA2. J Cell Physiol. 2019;234(11):21380–21394.
  • 19. Xu Y, Liu N, Wei Y, et al. Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells. Aging (Albany NY). 2020;12(19):19660–19676.
  • 20. Wang B, Xu Y, Wei Y, et al. Human mesenchymal stem cell-derived exosomal microRNA-143 promotes apoptosis and suppresses cell growth in pancreatic cancer via target gene regulation. Front Genet. 2021;12:581694.
  • 21. Kacaroglu D, Gurbuz N. Comparison of therapeutic potential of macrophage- or mesenchymal stem cell-derived exosomes in pancreatic cancer: An updated review. World J Stem Cells. 2025;17(8):107400.
  • 22. Ünal Halbutoğulları ZS, Utkan Korun ZE, Subaşı Demir C, Kılıç KC, Alper B, Yazır Y. Optimization of protein quantification in wharton jelly-derived mesenchymal stem cell exosomes. Acta Med Nicomedia. 2023;6(3):452-458.
  • 23. Ghasempour E, Hesami S, Movahed E, Keshel SH, Doroudian M. Mesenchymal stem cell-derived exosomes as a new therapeutic strategy in the brain tumors. Stem Cell Res Ther. 2022;13(1):527.
  • 24. Liu Y, Song B, Wei Y, et al. Exosomes from mesenchymal stromal cells enhance imatinib-induced apoptosis in human leukemia cells via activation of caspase signaling pathway. Cytotherapy. 2018;20(2):181-188.
  • 25. Takahara K, Ii M, Inamoto T, et al. MicroRNA-145 mediates the inhibitory effect of adipose tissue-derived stromal cells on prostate cancer. Stem Cells Dev. 2016;25(17):1290-1298.
  • 26. Karaoz E, Sun E, Demir CS. Mesenchymal stem cell-derived exosomes do not promote the proliferation of cancer cells in vitro. Int J Physiol Pathophysiol Pharmacol. 2019;11(4):177-189.
  • 27. Rezaeian A, Khatami F, Heidari Keshel S, et al. The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines. Sci Rep. 2022;12(1):20924.
  • 28. Ding Y, Cao F, Sun H, et al. Exosomes derived from human umbilical cord mesenchymal stromal cells deliver exogenous miR-145-5p to inhibit pancreatic ductal adenocarcinoma progression. Cancer Lett. 2019;442:351-361.
  • 29. Shang S, Wang J, Chen S, et al. Exosomal miRNA-1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer. Cancer Med. 2019;8(18):7728-7740.
  • 30. Kumar D, Gupta D, Shankar S, Srivastava RK. Biomolecular characterization of exosomes released from cancer stem cells: Possible implications for biomarker and treatment of cancer. Oncotarget. 2015;6(5):3280-3291.
  • 31. Maia J, Caja S, Strano Moraes MC, Couto N, Costa-Silva B. Exosome-based cell-cell communication in the tumor microenvironment. Front Cell Dev Biol. 2018;6:18.
  • 32. Lin R, Wang S, Zhao RC. Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model. Mol Cell Biochem. 2013;383(1-2):13-20.
  • 33. Del Fattore A, Luciano R, Saracino R, et al. Differential effects of extracellular vesicles secreted by mesenchymal stem cells from different sources on glioblastoma cells. Expert Opin Biol Ther. 2015;15(4):495-504.
  • 34. Bruno S, Collino F, Deregibus MC, Grange C, Tetta C, Camussi G. Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth. Stem Cells Dev. 2014;23(24):3072.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Rejeneratif Tıp (kök hücreler dahil)
Bölüm Araştırma Makalesi
Yazarlar

Demet Kaçaroğlu 0000-0003-4920-0516

Alper Murat Ulaşlı 0000-0001-8872-1432

Seher Yaylacı 0000-0003-3309-2303

Gönderilme Tarihi 16 Ağustos 2024
Kabul Tarihi 10 Kasım 2025
Yayımlanma Tarihi 31 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Sayı: 27

Kaynak Göster

JAMA Kaçaroğlu D, Ulaşlı AM, Yaylacı S. Exploring the Effects of WJ-MSC-Derived Exosomes on the Viability and Metabolic Activity of Lung, Pancreatic and Liver Cancer Cells. IGUSABDER. 2025;:824–836.

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