Increasing Apoptotic Effect of Cord Blood and Wharton's Jelly-derived Mesenchymal Stem Cells on HT-29

Page: [1133 - 1141] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Recently, mesenchymal stem cells (MSCs) have been considered a suitable cell therapy option for cancer due to their high migration rate to the tumor site.

Objectives: The study aimed to compare the effects of human umbilical cord blood derived-MSC (UCMSC) and human Wharton’s Jelly derived-MSC (WJ-MSC) on the HT-29 cell line.

Methods: UC-MSC was obtained by Ficoll-Paque density gradient and WJ-MSC by explant method. The characterizations of MSCs and apoptosis assays were performed by flow cytometry, and caspase-3 protein levels were measured by ELISA.

Results: After 72 hours of HT-29 cancer cells incubation, it was indicated that WJ-MSC was more effective at 1:5 and 1:10 ratios. Similar results were found for caspase-3 by ELISA. Moreover, WJ-MSC (1:5, p < 0.006; 1:10, p < 0.007) was found to be more effective at both doses compared to UC-MSC.

Conclusion: In this study, we used two different MSC sources at two different ratios to evaluate the apoptotic effect of MSC in vitro on HT-29 CRC cells. As a result, WJ-MSC indicated a more apoptotic effect on HT-29 cells compared to CB-MSC. We anticipated that this preliminary in vitro study would be extended in future in vitro/in vivo studies. Moreover, investigating the behavior of MSC in colorectal tumor microenvironment will be beneficial for the stem cell therapy approach.

Graphical Abstract

[1]
Balchen V, Simon K. Colorectal cancer development and advances in screening. Clin Interv Aging 2016; 11: 967-76.
[http://dx.doi.org/10.2147/CIA.S109285] [PMID: 27486317]
[2]
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Wang S, Miao Z, Yang Q, Wang Y, Zhang J. The dynamic roles of mesenchymal stem cells in colon cancer. Can J Gastroenterol Hepatol 2018; 2018: 7628763.
[http://dx.doi.org/10.1155/2018/7628763] [PMID: 30533404]
[4]
Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet 2016; 7(3): 105-14.
[PMID: 27766137]
[5]
Hmadcha A, Martin-Montalvo A, Gauthier BR, Soria B, Capilla-Gonzalez V. Therapeutic potential of mesenchymal stem cells for cancer therapy. Front Bioeng Biotechnol 2020; 8: 43.
[http://dx.doi.org/10.3389/fbioe.2020.00043] [PMID: 32117924]
[6]
Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2018; 93(1): 19-31.
[http://dx.doi.org/10.1002/cyto.a.23242] [PMID: 29072818]
[7]
Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315-7.
[http://dx.doi.org/10.1080/14653240600855905] [PMID: 16923606]
[8]
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 Bank 2019; 20(3): 423-34.
[http://dx.doi.org/10.1007/s10561-019-09781-8] [PMID: 31338647]
[9]
Ahn SY. The role of MSCs in the tumor microenvironment and tumor progression. Anticancer Res 2020; 40(6): 3039-47.
[http://dx.doi.org/10.21873/anticanres.14284] [PMID: 32487597]
[10]
Rodríguez-Fuentes DE, Fernández-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldaña HA. Mesenchymal stem cells current clinical applications: A systematic review. Arch Med Res 2021; 52(1): 93-101.
[http://dx.doi.org/10.1016/j.arcmed.2020.08.006] [PMID: 32977984]
[11]
Yoo J, Kim CH, Song SH, et al. Expression of caspase-3 and c-myc in non-small cell lung cancer. Cancer Res Treat 2004; 36(5): 303-7.
[http://dx.doi.org/10.4143/crt.2004.36.5.303] [PMID: 20368820]
[12]
Pu X, Storr SJ, Zhang Y, et al. Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival. Apoptosis 2017; 22(3): 357-68.
[http://dx.doi.org/10.1007/s10495-016-1323-5] [PMID: 27798717]
[13]
Asadi M, Shanehbandi D, Asvadi Kermani T, Sanaat Z, Zafari V, Hashemzadeh S. Expression level of caspase genes in colorectal cancer. Asian Pac J Cancer Prev 2018; 19(5): 1277-80.
[PMID: 29801534]
[14]
Tan YS, Lei YL. Isolation of tumor-ınfiltrating lymphocytes by ficoll-paque density gradient centrifugation. Methods Mol Biol 2019; 1960: 93-9.
[http://dx.doi.org/10.1007/978-1-4939-9167-9_8] [PMID: 30798524]
[15]
Skiles ML, Marzan AJ, Brown KS, Shamonki JM. Comparison of umbilical cord tissue-derived mesenchymal stromal cells isolated from cryopreserved material and extracted by explantation and digestion methods utilizing a split manufacturing model. Cytotherapy 2020; 22(10): 581-91.
[http://dx.doi.org/10.1016/j.jcyt.2020.06.002] [PMID: 32718875]
[16]
Martínez-Maqueda D, Miralles B, Recio I. HT29 cell line. In: Verhoeckx K, Cotter P, López-Expósito I, Eds. The Impact of Food Bioactivity on Health: in vitro and ex vivo models. Cham: Springer Nature 2015; pp. 113-24.
[17]
Morata-Tarifa C, Jiménez G, García MA, et al. Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells. Sci Rep 2016; 6(1): 18772.
[http://dx.doi.org/10.1038/srep18772] [PMID: 26752044]
[18]
Renaud J, Martinoli MG. Development of an insert co-culture system of two cellular types in the absence of cell-cell contact. J Vis Exp 2016; 113: 10.3791/54356.
[http://dx.doi.org/10.3791/54356] [PMID: 27500972]
[19]
Crowley LC, Marfell BJ, Scott AP, Waterhouse NJ. Quantitation of apoptosis and necrosis by Annexin V binding, propidium iodide uptake, and flow cytometry. Cold Spring Harb Protoc 2016; 2016(11): pdb.prot087288.
[http://dx.doi.org/10.1101/pdb.prot087288] [PMID: 27803250]
[20]
Rosell A, Cuadrado E, Alvarez-Sabín J, et al. Caspase-3 is related to infarct growth after human ischemic stroke. Neurosci Lett 2008; 430(1): 1-6.
[http://dx.doi.org/10.1016/j.neulet.2007.05.006] [PMID: 18055116]
[21]
Bharti D, Belame Shivakumar S, Baregundi Subbarao R, Rho GJ. Research advancements in porcine derived mesenchymal stem cells. Curr Stem Cell Res Ther 2016; 11(1): 78-93.
[http://dx.doi.org/10.2174/1574888X10666150723145911] [PMID: 26201864]
[22]
Chang HY, Yang X. Proteases for cell suicide: Functions and regulation of caspases. Microbiol Mol Biol Rev 2000; 64(4): 821-46.
[http://dx.doi.org/10.1128/MMBR.64.4.821-846.2000] [PMID: 11104820]
[23]
Mirabdollahi M, Sadeghi-Aliabadi H, Haghjooy Javanmard S. Human Wharton’s jelly mesenchymal stem cells-derived secretome could inhibit breast cancer growth in vitro and in vivo. Iran J Basic Med Sci 2020; 23(7): 945-53.
[PMID: 32774818]
[24]
Rezaei-Tazangi F, Alidadi H, Samimi A, Karimi S, Kahorsandi L. Effects of Wharton’s jelly mesenchymal stem cells-derived secretome on colon carcinoma HT-29 cells. Tissue Cell 2020; 67: 101413.
[http://dx.doi.org/10.1016/j.tice.2020.101413] [PMID: 32835945]
[25]
Tang R, Shen S, Zhao X, et al. Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer. Stem Cell Res Ther 2015; 6(1): 71.
[http://dx.doi.org/10.1186/s13287-015-0055-8] [PMID: 25889203]
[26]
Kim HS, Shin TH, Lee BC, et al. Human umbilical cord blood mesenchymal stem cells reduce colitis in mice by activating NOD2 signaling to COX2. Gastroenterology 2013; 145(6): 1392-1403.e8, 8.
[http://dx.doi.org/10.1053/j.gastro.2013.08.033] [PMID: 23973922]
[27]
Hass R. Role of MSC in the tumor microenvironment. Cancers 2020; 12(8): 2107.
[http://dx.doi.org/10.3390/cancers12082107] [PMID: 32751163]
[28]
Hass R, von der Ohe J, Ungefroren H. Potential role of MSC/cancer cell fusion and EMT for breast cancer stem cell formation. Cancers 2019; 11(10): 1432.
[http://dx.doi.org/10.3390/cancers11101432] [PMID: 31557960]
[29]
Nishikawa G, Kawada K, Nakagawa J, et al. Bone marrow-derived mesenchymal stem cells promote colorectal cancer progression via CCR5. Cell Death Dis 2019; 10(4): 264.
[http://dx.doi.org/10.1038/s41419-019-1508-2] [PMID: 30890699]