From laboratory studies to clinical applications mesenchymal stem cells in cancer treatment: Translational oncology

Year 2023, Volume: 40 Issue: 1, 171 - 179, 18.03.2023

Melek Yüce

Abstract

Stem cell-based studies have accelerated to treat various pathologies, particularly neurological, cardiovascular, orthopedic diseases and cancer with the understanding of their therapeutic potential after their discovery. Stem cells have recently aroused great interest as a promising treatment option in the fighting to cancer with extensive study in the fields of cancer biology. Nevertheless, much uncertainty regarding the act of stem cells in cancer development and treatment remains obscure before the clinical use of stem cell investigation. Despite many obstacles, the migration ability of stem cells, the bioactive factors they secrete, and their immune regulatory properties make them advantageous for gene therapy strategies. However, unknowns and a lack of scientific data remain concerning the use of stem cell based therapies. Therefore, more experimental data are needed to confirm the different study results presented by different scientific communities. In this review, we focused on summarizing the available experimental and clinical data on the potential uses of mesenchymal stem cells in cancer therapy.

Keywords

Anti-tumoral activity, cellular therapy, cancer, mesenchymal stem cells

Supporting Institution

-

Project Number

-

Thanks

The author would like to thank Esra Albayrak for editing the writing.

References

• Friedenstein, A., R. Chailakhjan, and K. Lalykina, The development of fibroblast colonies in monolayer cultures of guinea‐pig bone marrow and spleen cells. Cell Proliferation, 1970. 3(4): p. 393-403.
• Čamernik, K., et al., Skeletal-muscle-derived mesenchymal stem/stromal cells from patients with osteoarthritis show superior biological properties compared to bone-derived cells. Stem Cell Research, 2019. 38: p. 101465.
• Wu, G., et al., Osteogenesis of peripheral blood mesenchymal stem cells in self assembling peptide nanofiber for healing critical size calvarial bony defect. Scientific reports, 2015. 5(1): p. 1-12.
• Wang, B., et al., Human hair follicle-derived mesenchymal stem cells: Isolation, expansion, and differentiation. World Journal of Stem Cells, 2020. 12(6): p. 462.
• Ledesma-Martínez, E., V.M. Mendoza-Núñez, and E. Santiago-Osorio, Mesenchymal stem cells derived from dental pulp: a review. Stem cells international, 2016. 2016.
• Wu, M., et al., Comparison of the biological characteristics of mesenchymal stem cells derived from the human placenta and umbilical cord. Scientific Reports, 2018. 8(1): p. 1-9.
• Mazini, L., et al., Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs). International journal of molecular sciences, 2019. 20(10): p. 2523.
• Hmadcha, A., et al., Therapeutic potential of mesenchymal stem cells for cancer therapy. Frontiers in Bioengineering and Biotechnology, 2020. 8: p. 43.
• Lv, F.-J., et al., Concise review: the surface markers and identity of human mesenchymal stem cells. Stem cells, 2014. 32(6): p. 1408-1419.
• Sheng, G., The developmental basis of mesenchymal stem/stromal cells (MSCs). BMC Developmental Biology, 2015. 15(1): p. 1-8.
• Pittenger, M.F., et al., Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regenerative medicine, 2019. 4(1): p. 1-15.
• Bonab, M.M., et al., Aging of mesenchymal stem cell in vitro. BMC cell biology, 2006. 7(1): p. 1-7.
• Choudhery, M.S., et al., Donor age negatively impacts adipose tissue-derived mesenchymal stem cell expansion and differentiation. Journal of translational medicine, 2014. 12(1): p. 1-14.
• Granero-Moltó, F., et al., Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem cells, 2009. 27(8): p. 1887-1898.
• Iijima, H., et al., Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: a meta-analysis toward the establishment of effective regenerative rehabilitation. NPJ Regenerative medicine, 2018. 3(1): p. 1-13.
• Mathiasen, A.B., et al., Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial). European heart journal, 2015. 36(27): p. 1744-1753.
• Mathiasen, A.B., et al., Bone marrow‐derived mesenchymal stromal cell treatment in patients with ischaemic heart failure: final 4‐year follow‐up of the MSC‐HF trial. European journal of heart failure, 2020. 22(5): p. 884-892.
• Donega, V., et al., Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury. Experimental neurology, 2014. 261: p. 53-64.
• McGrath, A.M., et al., Fibrin conduit supplemented with human mesenchymal stem cells and immunosuppressive treatment enhances regeneration after peripheral nerve injury. Neuroscience letters, 2012. 516(2): p. 171-176.
• Fouraschen, S.M., et al., Secreted factors of human liver-derived mesenchymal stem cells promote liver regeneration early after partial hepatectomy. Stem cells and development, 2012. 21(13): p. 2410-2419.
• Ullah, M., et al., Reversing acute kidney injury using pulsed focused ultrasound and MSC therapy: a role for HSP-mediated PI3K/AKT signaling. Molecular Therapy-Methods & Clinical Development, 2020. 17: p. 683-694.
• Berry, M.F., et al., Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. American Journal of Physiology-Heart and Circulatory Physiology, 2006. 290(6): p. H2196-H2203.
• Si, Y., et al., Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes, 2012. 61(6): p. 1616-1625.
• Brenner, A.K., I. Nepstad, and Ø. Bruserud, Mesenchymal stem cells support survival and proliferation of primary human acute myeloid leukemia cells through heterogeneous molecular mechanisms. Frontiers in immunology, 2017. 8: p. 106.
• Di, G.-h., et al., IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells. PloS one, 2014. 9(11): p. e113572.
• Li, T., et al., Umbilical cord-derived mesenchymal stem cells promote proliferation and migration in MCF-7 and MDA-MB-231 breast cancer cells through activation of the ERK pathway. Oncology reports, 2015. 34(3): p. 1469-1477.
• Liu, C., et al., Bone marrow mesenchymal stem cells interact with head and neck squamous cell carcinoma cells to promote cancer progression and drug resistance. Neoplasia, 2021. 23(1): p. 118-128.
• Wu, X.-B., et al., Mesenchymal stem cells promote colorectal cancer progression through AMPK/mTOR-mediated NF-κB activation. Scientific reports, 2016. 6(1): p. 1-12.
• Ayuzawa, R., et al., Naive human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo. Cancer letters, 2009. 280(1): p. 31-37.
• Cousin, B., et al., Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo. PloS one, 2009. 4(7): p. e6278.
• Dhiman, N., et al., 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): p. 25-36.
• Fathi, E., et al., Cytokines secreted from bone marrow derived mesenchymal stem cells promote apoptosis and change cell cycle distribution of K562 cell line as clinical agent in cell transplantation. PloS one, 2019. 14(4): p. e0215678.
• Fonseka, M., et al., Human umbilical cord blood‐derived mesenchymal stem cells (hUCB‐MSC) inhibit the proliferation of K562 (human erythromyeloblastoid leukaemic cell line). Cell biology international, 2012. 36(9): p. 793-801.
• Ganta, C., et al., Rat umbilical cord stem cells completely abolish rat mammary carcinomas with no evidence of metastasis or recurrence 100 days post–tumor cell inoculation. Cancer research, 2009. 69(5): p. 1815-1820.
• Gauthaman, K., et al., Human umbilical cord Wharton's jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro. Journal of cellular biochemistry, 2012. 113(6): p. 2027-2039.
• Khalil, C., et al., Anti-proliferative effects of mesenchymal stem cells (MSCs) derived from multiple sources on ovarian cancer cell lines: an in-vitro experimental study. Journal of Ovarian Research, 2019. 12(1): p. 1-12.
• Larmonier, N., et al., Freshly isolated bone marrow cells induce death of various carcinoma cell lines. International journal of cancer, 2003. 107(5): p. 747-756.
• Lim, Y.-S., et al., Growth inhibitory effect of palatine tonsil-derived mesenchymal stem cells on head and neck squamous cell carcinoma cells. Clinical and Experimental Otorhinolaryngology, 2012. 5(2): p. 86.
• Maj, M., et al., Influence of mesenchymal stem cells conditioned media on proliferation of urinary tract cancer cell lines and their sensitivity to ciprofloxacin. Journal of Cellular Biochemistry, 2017. 118(6): p. 1361-1368.
• Motaln, H., et al., Human mesenchymal stem cells exploit the immune response mediating chemokines to impact the phenotype of glioblastoma. Cell transplantation, 2012. 21(7): p. 1529-1545.
• Bortolotti, F., et al., In vivo therapeutic potential of mesenchymal stromal cells depends on the source and the isolation procedure. Stem cell reports, 2015. 4(3): p. 332-339.
• Lin, W., et al., Mesenchymal stem cells and cancer: clinical challenges and opportunities. BioMed Research International, 2019. 2019.
• Zachar, L., D. Bačenková, and J. Rosocha, Activation, homing, and role of the mesenchymal stem cells in the inflammatory environment. Journal of inflammation research, 2016. 9: p. 231.
• Akimoto, K., et al., Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation. Stem cells and development, 2013. 22(9): p. 1370-1386.
• Serhal, R., et al., Effect of adipose-derived mesenchymal stem cells on hepatocellular carcinoma: In vitro inhibition of carcinogenesis. World journal of gastroenterology, 2019. 25(5): p. 567.
• Li, X. and Z. Li, Effects of human umbilical cord mesenchymal stem cells on co‐cultured ovarian carcinoma cells. Microscopy Research and Technique, 2019. 82(6): p. 898-902.
• Yang, X., et al., Human umbilical cord mesenchymal stem cells promote carcinoma growth and lymph node metastasis when co-injected with esophageal carcinoma cells in nude mice. Cancer cell international, 2014. 14(1): p. 1-11.
• Kang, S.-G., et al., Cytotoxicity of human umbilical cord blood-derived mesenchymal stem cells against human malignant glioma cells. Child's Nervous System, 2008. 24(3): p. 293-302.
• Liu, J., et al., Quantitative Tracking Tumor Suppression Efficiency of Human Umbilical Cord-Derived Mesenchymal Stem Cells by Bioluminescence Imaging in Mice Hepatoma Model. International journal of stem cells, 2020. 13(1): p. 104-115.
• Zhao, J., et al., Effect of umbilical cord mesenchymal stem cells on biological characteristics of esophageal cancer EC1 cells. Zhonghua zhong liu za zhi [Chinese journal of oncology], 2019. 41(2): p. 97-101.
• Khakoo, A.Y., et al., Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. The Journal of experimental medicine, 2006. 203(5): p. 1235-1247.
• Li, Q., et al., Effects of human umbilical cord-derived mesenchymal stem cells on hematologic malignancies. Oncology Letters, 2018. 15(5): p. 6982-6990.
• Ramasamy, R., et al., Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia, 2007. 21(2): p. 304-310.
• Song, N., et al., Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant. International journal of molecular medicine, 2015. 36(1): p. 139-149.
• Zhu, Y., et al., Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia, 2009. 23(5): p. 925-933.
• Secchiero, P., et al., Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts. PloS one, 2010. 5(6): p. e11140.
• Lee, M.W., et al., Human adipose tissue stem cells promote the growth of acute lymphoblastic leukemia cells in NOD/SCID mice. Stem Cell Reviews and Reports, 2018. 14(3): p. 451-460.
• Lee, M.W., et al., Mesenchymal stem cells in suppression or progression of hematologic malignancy: current status and challenges. Leukemia, 2019. 33(3): p. 597-611.
• Gunawardena, T.N.A., et al., Conditioned media derived from mesenchymal stem cell cultures: The next generation for regenerative medicine. Journal of tissue engineering and regenerative medicine, 2019. 13(4): p. 569-586.
• Sagaradze, G., et al., Conditioned medium from human mesenchymal stromal cells: towards the clinical translation. International journal of molecular sciences, 2019. 20(7): p. 1656.
• Bhang, S.H., et al., Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis. Molecular Therapy, 2014. 22(4): p. 862-872.
• Pawitan, J.A., Prospect of stem cell conditioned medium in regenerative medicine. BioMed research international, 2014. 2014.
• Xie, L., et al., Signal factors secreted by 2D and spheroid mesenchymal stem cells and by cocultures of mesenchymal stem cells derived microvesicles and retinal photoreceptor neurons. Stem cells international, 2017. 2017.
• Onzi, G.R., et al., Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Cytotherapy, 2016. 18(7): p. 828-837.
• Cortes-Dericks, L., et al., Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines. Stem cell research & therapy, 2016. 7(1): p. 1-8.
• Hendijani, F., et al., Effect of human Wharton's jelly mesenchymal stem cell secretome on proliferation, apoptosis and drug resistance of lung cancer cells. Research in Pharmaceutical Sciences, 2015. 10(2): p. 134.
• Li, L., et al., Inhibition of lung cancer cell proliferation mediated by human mesenchymal stem cells. Acta Biochim Biophys Sin, 2011. 43(2): p. 143-148.
• Mirabdollahi, M., S. Haghjooyjavanmard, and H. Sadeghi-Aliabadi, An anticancer effect of umbilical cord-derived mesenchymal stem cell secretome on the breast cancer cell line. Cell and tissue banking, 2019. 20(3): p. 423-434.
• Zhou, J., et al., Mesenchymal stem cell derived exosomes in cancer progression, metastasis and drug delivery: a comprehensive review. Journal of Cancer, 2018. 9(17): p. 3129.
• Hassanzadeh, A., et al., Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities. Stem cell research & therapy, 2021. 12(1): p. 1-22.
• Sohrabi, B., et al., Mesenchymal stem cell (msc)-derived exosomes as novel vehicles for delivery of mirnas in cancer therapy. Cancer Gene Therapy, 2022: p. 1-12.
• Yin, K., S. Wang, and R.C. Zhao, Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm. Biomarker research, 2019. 7(1): p. 1-8.
• Yassine, S. and N. Alaaeddine, Mesenchymal stem cell exosomes and cancer: controversies and prospects. Advanced Biology, 2022. 6(2): p. 2101050.
• Lin, R., S. Wang, and R.C. Zhao, Exosomes from human adipose-derived mesenchymal stem cells promote migration through Wnt signaling pathway in a breast cancer cell model. Molecular and cellular biochemistry, 2013. 383(1): p. 13-20.
• Lee, J.-K., et al., Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PloS one, 2013. 8(12): p. e84256.
• Zhu, W., et al., Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer letters, 2012. 315(1): p. 28-37.
• Gu, H., et al., Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway. Molecular medicine reports, 2016. 14(4): p. 3452-3458.
• Wu, S., et al., 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): p. e61366.
• Kalimuthu, S., et al., In vivo therapeutic potential of mesenchymal stem cell-derived extracellular vesicles with optical imaging reporter in tumor mice model. Scientific reports, 2016. 6(1): p. 1-11.
• Mendt, M., et al., Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI insight, 2018. 3(8).