Research Article
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Conditioned media of tonsil derived mesenchymal stem cells shows different rates of cytotoxicity on solid cancer cells

Year 2023, Volume: 5 Issue: 4, 503 - 510, 27.10.2023
https://doi.org/10.38053/acmj.1359905

Abstract

Aims: Mesenchymal stem cells (MSCs) are the apple of the eye of cancer studies. It was indicated that the secreted factors, especially released by MSCs, have tumoral or anti-tumoral effects on tumor progression. MSCs obtained from different sources show different anti-tumoral effects, while MSCs originating from the same source also show different tumoral effects in different cancer cells. Here, we investigated the anti-tumor effects of soluble factors secreted from palatine tonsil MSCs (TMSC) as a new source of MSC on human lung carcinoma (A549) and pancreatic cancer (PANC-1) cell lines.
Methods: Conditioned medium (CM) was obtained from TMSCs isolated from palatine tonsil tissue, and the cytotoxic effect of CM on the growth of A549 and PANC-1 in a dose-dependent manner was demonstrated by MTT analysis. In addition, the function of CM treatment on the cell cycle status of cancer cells and the apoptosis process were investigated through cell cycle analysis with propidium iodide (PI) and Annexin-V/PI detection method by flow cytometry analysis, respectively.
Results: We demonstrated that TMSC-CM treatment significantly decreased the viability of A549 and PANC-1 cell lines in a dose-dependent manner post-48 hours. In addition, CM treatment differentially induced the apoptosis on A549 and PANC-1 cells and also, caused G2/M arrest in the cells.
Conclusion: In light of these findings, our study is the first to show that TMSC-CM has an anti-tumoral effect by stimulating apoptosis on A549 and PANC-1 cells. These findings reveal that the usage of CM has a cell-free cellular therapeutic potential.

Ethical Statement

OMÜ Klinik Araştırmalar Etik Kurulu OMÜ KAEK 2021/347

Thanks

We would like to thank Assoc. Dr. Fatih Kocabaş, Yeditepe University Department of Genetics and Bioengineering faculty member for generously granting the cancer cell lines.

References

  • Chu D-T, Nguyen TT, Tien NLB, et al. Recent progress of stem cell therapy in cancer treatment: molecular mechanisms and potential applications. Cells. 2020;9(3):563.
  • Raj AT, Kheur S, Bhonde R, Gupta AA, Patil S. Assessing the effect of human mesenchymal stem cell-derived conditioned media on human cancer cell lines: a systematic review. Tissue Cell. 2021;71:101505.
  • Bhang SH, Lee S, Shin J-Y, Lee T-J, Jang H-K, Kim B-S. Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis. Molecul Ther. 2014;22(4):862-872.
  • Gunawardena TNA, Rahman MT, Abdullah BJJ, Abu Kasim NH. Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine. J Tissue Eng Regen Med. 2019;13(4):569-586.
  • Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. BioMed Res Int. 2014;2014
  • Oh S-Y, Choi YM, Kim HY, et al. Application of tonsil-derived mesenchymal stem cells in tissue regeneration: concise review. Stem Cells. 2019;37(10):1252-1260.
  • Cho K-A, Park M, Kim Y-H, Woo S-Y, Ryu K-H. RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells from bone marrow, adipose tissue, and palatine tonsils. Scientific Rep. 2017;7(1):17114.
  • Cho K-A, Lee HJ, Jeong H, et al. Tonsil-derived stem cells as a new source of adult stem cells. World J Stem Cells. 2019;11(8):506.
  • Gauthaman K, Yee FC, Cheyyatraivendran S, Biswas A, Choolani M, Bongso A. Human umbilical cord Wharton’s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro. J Cell Biochem. 2012;113(6):2027-2039.
  • Lin DH, Biswas A, Choolani M, Fong C-Y, Bongso A. Induction of immunogenic cell death in lymphoma cells by Wharton’s jelly mesenchymal stem cell conditioned medium. Stem Cell Rev Rep. 2017;13:801-816.
  • Onzi GR, Ledur PF, Hainzenreder LD, et al. Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Cytotherapy. 2016;18(7):828-837.
  • Cortes-Dericks L, Froment L, Kocher G, Schmid RA. Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines. Stem Cell Res Ther. 2016;7:1-8.
  • Hendijani F, Javanmard SH, Rafiee L, Sadeghi-Aliabadi H. Effect of human Wharton’s jelly mesenchymal stem cell secretome on proliferation, apoptosis and drug resistance of lung cancer cells. Res Pharmaceutical Sci. 2015;10(2):134.
  • Li L, Tian H, Chen Z, Yue W, Li S, Li W. Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells. Acta Biochim Biophys Sin. 2011;43(2):143-148.
  • Mirabdollahi M, Haghjooyjavanmard S, Sadeghi-Aliabadi H. An anticancer effect of umbilical cord-derived mesenchymal stem cell secretome on the breast cancer cell line. Cell Tissue Banking. 2019;20:423-434.
  • Lim Y-S, Lee J-C, Lee YS, Lee B-J, Wang S-G. Growth inhibitory effect of palatine tonsil-derived mesenchymal stem cells on head and neck squamous cell carcinoma cells. Clin Exp Otorhinolaryngol. 2012;5(2):86-93.
  • Yüce M, Albayrak E. Hyperthermia‐stimulated tonsil‐mesenchymal stromal cells suppress hematological cancer cells through downregulation of IL‐6. J Cell Biochem. 2022;123(12):1966-1979.
  • Mancini SJ, Balabanian K, Corre I, et al. Deciphering tumor niches: Lessons from solid and hematological malignancies. Front Immunol. 2021;12:766275.
  • Slingerland M, Guchelaar H-J, Gelderblom H. Histone deacetylase inhibitors: an overview of the clinical studies in solid tumors. Anti-Cancer Drugs. 2014;25(2):140-149.
  • Dhiman N, Shagaghi N, Bhave M, Sumer H, Kingshott P, Rath SN. Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model. Cytotherapy. 2021;23(1):25-36.
  • Qiao L, Xu Z, Zhao T, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18(4):500-507.
  • Khakoo AY, Pati S, Anderson SA, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006;203(5):1235-1247.
  • Bagheri R, Bitazar R, Talebi S, Alaeddini M, Etemad-Moghadam S, Eini L. Conditioned media derived from mesenchymal stem cells induces apoptosis and decreases cell viability and proliferation in squamous carcinoma cell lines. Gene. 2021;782:145542.
  • Shah K. Mesenchymal stem cells engineered for cancer therapy. Adv Drug Delivery Rev. 2012;64(8):739-748.
  • Eiró N, Sendon-Lago J, Seoane S, et al. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells. Oncotarget. 2014;5(21):10692.
  • Pan M, Hou L, Zhang J, et al. Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells. Molecul Cell Biochem. 2018;441:63-76.
  • Magatti M, De Munari S, Vertua E, Parolini O. Amniotic membrane‐derived cells inhibit proliferation of cancer cell lines by inducing cell cycle arrest. J Cell Molecul Med. 2012;16(9):2208-2218.
  • Rolfo A, Giuffrida D, Giuffrida MC, Todros T, Calogero AE. New perspectives for prostate cancer treatment: in vitro inhibition of LNCaP and PC3 cell proliferation by amnion-derived mesenchymal stromal cells conditioned media. Aging Male. 2014;17(2):94-101.
  • Cho K, Lee H, Jeong H, Kim M, Jung S, Park H. Tonsil-derived stem cells as a new source of adult stem cells. World J Stem Cells. 2019;11(8):506-518.
  • Ryu K-H, Cho K-A, Park HS, et al. Tonsil-derived mesenchymal stromal cells: evaluation of biologic, immunologic and genetic factors for successful banking. Cytotherapy. 2012;14(10):1193-1202.
Year 2023, Volume: 5 Issue: 4, 503 - 510, 27.10.2023
https://doi.org/10.38053/acmj.1359905

Abstract

References

  • Chu D-T, Nguyen TT, Tien NLB, et al. Recent progress of stem cell therapy in cancer treatment: molecular mechanisms and potential applications. Cells. 2020;9(3):563.
  • Raj AT, Kheur S, Bhonde R, Gupta AA, Patil S. Assessing the effect of human mesenchymal stem cell-derived conditioned media on human cancer cell lines: a systematic review. Tissue Cell. 2021;71:101505.
  • Bhang SH, Lee S, Shin J-Y, Lee T-J, Jang H-K, Kim B-S. Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis. Molecul Ther. 2014;22(4):862-872.
  • Gunawardena TNA, Rahman MT, Abdullah BJJ, Abu Kasim NH. Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine. J Tissue Eng Regen Med. 2019;13(4):569-586.
  • Pawitan JA. Prospect of stem cell conditioned medium in regenerative medicine. BioMed Res Int. 2014;2014
  • Oh S-Y, Choi YM, Kim HY, et al. Application of tonsil-derived mesenchymal stem cells in tissue regeneration: concise review. Stem Cells. 2019;37(10):1252-1260.
  • Cho K-A, Park M, Kim Y-H, Woo S-Y, Ryu K-H. RNA sequencing reveals a transcriptomic portrait of human mesenchymal stem cells from bone marrow, adipose tissue, and palatine tonsils. Scientific Rep. 2017;7(1):17114.
  • Cho K-A, Lee HJ, Jeong H, et al. Tonsil-derived stem cells as a new source of adult stem cells. World J Stem Cells. 2019;11(8):506.
  • Gauthaman K, Yee FC, Cheyyatraivendran S, Biswas A, Choolani M, Bongso A. Human umbilical cord Wharton’s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro. J Cell Biochem. 2012;113(6):2027-2039.
  • Lin DH, Biswas A, Choolani M, Fong C-Y, Bongso A. Induction of immunogenic cell death in lymphoma cells by Wharton’s jelly mesenchymal stem cell conditioned medium. Stem Cell Rev Rep. 2017;13:801-816.
  • Onzi GR, Ledur PF, Hainzenreder LD, et al. Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Cytotherapy. 2016;18(7):828-837.
  • Cortes-Dericks L, Froment L, Kocher G, Schmid RA. Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines. Stem Cell Res Ther. 2016;7:1-8.
  • Hendijani F, Javanmard SH, Rafiee L, Sadeghi-Aliabadi H. Effect of human Wharton’s jelly mesenchymal stem cell secretome on proliferation, apoptosis and drug resistance of lung cancer cells. Res Pharmaceutical Sci. 2015;10(2):134.
  • Li L, Tian H, Chen Z, Yue W, Li S, Li W. Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells. Acta Biochim Biophys Sin. 2011;43(2):143-148.
  • Mirabdollahi M, Haghjooyjavanmard S, Sadeghi-Aliabadi H. An anticancer effect of umbilical cord-derived mesenchymal stem cell secretome on the breast cancer cell line. Cell Tissue Banking. 2019;20:423-434.
  • Lim Y-S, Lee J-C, Lee YS, Lee B-J, Wang S-G. Growth inhibitory effect of palatine tonsil-derived mesenchymal stem cells on head and neck squamous cell carcinoma cells. Clin Exp Otorhinolaryngol. 2012;5(2):86-93.
  • Yüce M, Albayrak E. Hyperthermia‐stimulated tonsil‐mesenchymal stromal cells suppress hematological cancer cells through downregulation of IL‐6. J Cell Biochem. 2022;123(12):1966-1979.
  • Mancini SJ, Balabanian K, Corre I, et al. Deciphering tumor niches: Lessons from solid and hematological malignancies. Front Immunol. 2021;12:766275.
  • Slingerland M, Guchelaar H-J, Gelderblom H. Histone deacetylase inhibitors: an overview of the clinical studies in solid tumors. Anti-Cancer Drugs. 2014;25(2):140-149.
  • Dhiman N, Shagaghi N, Bhave M, Sumer H, Kingshott P, Rath SN. Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model. Cytotherapy. 2021;23(1):25-36.
  • Qiao L, Xu Z, Zhao T, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18(4):500-507.
  • Khakoo AY, Pati S, Anderson SA, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006;203(5):1235-1247.
  • Bagheri R, Bitazar R, Talebi S, Alaeddini M, Etemad-Moghadam S, Eini L. Conditioned media derived from mesenchymal stem cells induces apoptosis and decreases cell viability and proliferation in squamous carcinoma cell lines. Gene. 2021;782:145542.
  • Shah K. Mesenchymal stem cells engineered for cancer therapy. Adv Drug Delivery Rev. 2012;64(8):739-748.
  • Eiró N, Sendon-Lago J, Seoane S, et al. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells. Oncotarget. 2014;5(21):10692.
  • Pan M, Hou L, Zhang J, et al. Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells. Molecul Cell Biochem. 2018;441:63-76.
  • Magatti M, De Munari S, Vertua E, Parolini O. Amniotic membrane‐derived cells inhibit proliferation of cancer cell lines by inducing cell cycle arrest. J Cell Molecul Med. 2012;16(9):2208-2218.
  • Rolfo A, Giuffrida D, Giuffrida MC, Todros T, Calogero AE. New perspectives for prostate cancer treatment: in vitro inhibition of LNCaP and PC3 cell proliferation by amnion-derived mesenchymal stromal cells conditioned media. Aging Male. 2014;17(2):94-101.
  • Cho K, Lee H, Jeong H, Kim M, Jung S, Park H. Tonsil-derived stem cells as a new source of adult stem cells. World J Stem Cells. 2019;11(8):506-518.
  • Ryu K-H, Cho K-A, Park HS, et al. Tonsil-derived mesenchymal stromal cells: evaluation of biologic, immunologic and genetic factors for successful banking. Cytotherapy. 2012;14(10):1193-1202.
There are 30 citations in total.

Details

Primary Language English
Subjects Regenerative Medicine (Incl. Stem Cells)
Journal Section Research Articles
Authors

Melek Yüce 0000-0002-3791-838X

Esra Albayrak 0000-0002-9114-6253

Çağrı Gümüşkaptan 0000-0002-8600-172X

Early Pub Date October 26, 2023
Publication Date October 27, 2023
Published in Issue Year 2023 Volume: 5 Issue: 4

Cite

AMA Yüce M, Albayrak E, Gümüşkaptan Ç. Conditioned media of tonsil derived mesenchymal stem cells shows different rates of cytotoxicity on solid cancer cells. Anatolian Curr Med J / ACMJ / acmj. October 2023;5(4):503-510. doi:10.38053/acmj.1359905

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