An Engineered Mesenchymal Stem Cell by Lentiviral Vector Expressing CD44 as a Candidate to Target Colon Cancer Tissue in Mice Model

Document Type : Original Research

Authors
A. Nabizadeh
M. Ravanshad
Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University
10.52547/iem.8.1.69
Abstract
Backgrounds: It is evident that the success of common cancer treatments is reduced due to limited drug access to tumor tissue, the drug toxicity intolerance in healthy cells, as well as the exposure of the immune system to the drug. Cancer stem cells are also a small population of tumor cells, which have different potentials for regeneration, proliferation, and differentiation and serve as a carcinogenic driving force. They are believed to play a key role in the onset, progression, drug resistance, recurrence of cancer, or metastasis. Although mesenchymal stem cells (MSC) have a slight ability to migrate toward the tumor, they could be considered as a cellular carrier for tumor targeting due to lack of recognition by the host immune system. Stem cells with their own ligands could effectively target cancer cells. One of the CD markers that exist on the surface of stem cells is CD44v6, which is considered as a homing receptor. Given that the expression level of stem cell markers is reduced during consecutive cultures in vitro environment; therefore, in the present study, stem cells were engineered using CD44 lentiviral vectors to more effectively improve the implantation and targeting of the colon cancer cell model.

Materials & Methods: In this study, the structure of the CD44 gene was designed in lentiviral vectors and transfected to the HEK293T cell line along with auxiliary plasmids PSPAX2 and PMDG2. The growth medium of virus-containing cells was collected at optimized intervals, and transduction into mice mesenchymal stem cells, injection into mice, and homing processes were traced.

Findings: Successful production of lentiviral vectors and proper expression of the corresponding factor after transduction were effective in improving the MSC homing in cancer cell.

Findings: According to these findings, it could be suggested that high expression of CD44v6 factor could be effective in improving the implantation process in cancer cells and targeting treatment.

Keywords

1. Stidham RW, Higgins PD. Translational Research in Colorectal Cancer: Colorectal Cancer in Inflammatory Bowel Disease. Clinics in colon and rectal surgery. 2018;31(3):168.
2. Hammond WA, Swaika A, Mody K. Pharmacologic resistance in colorectal cancer: a review. Therapeutic advances in medical oncology. 2016;8(1):57-84.
3. Van der Jeught K, Xu H-C, Li Y-J, Lu X-B, Ji G. Drug resistance and new therapies in colorectal cancer. World journal of gastroenterology. 2018;24(34):3834.
4. Zhai Z, Yu X, Yang B, Zhang Y, Zhang L, Li X, et al., editors. Colorectal cancer heterogeneity and targeted therapy: Clinical implications, challenges and solutions for treatment resistance. Seminars in cell & developmental biology; 2017: Elsevier.
5. Chou K-J, Lee P-T, Chen C-L, Hsu C-Y, Huang W-C, Huang C-W, et al. CD44 fucosylation on mesenchymal stem cell enhances homing and macrophage polarization in ischemic kidney injury. Experimental cell research. 2017;350(1):91-102.
6. Chulpanova DS, Kitaeva KV, Tazetdinova LG, James V, Rizvanov AA, Solovyeva VV. Application of mesenchymal stem cells for therapeutic agent delivery in anti-tumor treatment. Frontiers in pharmacology. 2018;9:259.
7. Squillaro T, Peluso G, Galderisi U. Clinical trials with mesenchymal stem cells: an update. Cell transplantation. 2016;25(5):829-48.
8. O’brien K, Khan S, Gilligan K, Zafar H, Lalor P, Glynn C, et al. Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379. Oncogene. 2018;37(16):2137-49.
9. Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. Journal of hematology & oncology. 2018;11(1):64.
10. Ma L, Dong L, Chang P. CD44v6 engages in colorectal cancer progression. Cell death & disease. 2019;10(1):1-13.
11. De Becker A, Van Riet I. Homing and migration of mesenchymal stromal cells: how to improve the efficacy of cell therapy? World journal of stem cells. 2016;8(3):73.
12. Das J, Choi Y-J, Yasuda H, Han JW, Park C, Song H, et al. Efficient delivery of C/EBP beta gene into human mesenchymal stem cells via polyethylenimine-coated gold nanoparticles enhances adipogenic differentiation. Scientific reports. 2016;6:33784.
13. Hill BS, Pelagalli A, Passaro N, Zannetti A. Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype. Oncotarget. 2017;8(42):73296.
14. Venkatesh V, Nataraj R, Thangaraj GS, Karthikeyan M, Gnanasekaran A, Kaginelli SB, et al. Targeting Notch signalling pathway of cancer stem cells. Stem cell investigation. 2018;5.
15. Ramdasi S, Sarang S, Viswanathan C. Potential of mesenchymal stem cell based application in cancer. International journal of hematology-oncology and stem cell research. 2015;9(2):95.
16. Su P, Tian Y, Yang C, Ma X, Wang X, Pei J, et al. Mesenchymal stem cell migration during bone formation and bone diseases therapy. International journal of molecular sciences. 2018;19(8):2343.
17. Morath I, Hartmann T, Orian-Rousseau V. CD44: More than a mere stem cell marker. The international journal of biochemistry & cell biology. 2016;81:166-73.
Infection Epidemiology and Microbiology
Volume 8, Issue 1
February 2022
Pages 69-76