Skip to main content

Advertisement

SpringerLink
Log in

Interplay between mesenchymal stem cell and tumor and potential application

  • Review Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Mesenchymal stem cells (MSCs) possess the capabilities of self-renewal and multipotent differentiation. Firstly isolated from bone marrow, MSCs are subsequently identified from various post-natal tissue types. Based the differentiation into tissue-specific cells, MSCs were capable of replacing damaged and diseased tissues. In addition, MSCs have been demonstrated to possess important immunomodulatory properties. Increasing data showed that MSCs exhibited tropism for sites of the tumor microenvironment and interacted with tumor cells closely through paracrine signaling. Therefore, better understanding of crosstalk between MSCs and tumor cells will be able to develop potential strategies in the treatment of tumors in the future. Herein, we summarize the research progress of the influence of MSCs on tumor cells and the prospect of their application in tumor therapy in this review.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002;418:41–9.

    CAS  PubMed  Google Scholar 

  2. Pratheesh MD, Gade NE, Katiyar AN, et al. Isolation, culture and characterization of caprine mesenchymal stem cells derived from amniotic fluid. Res Vet Sci. 2013;4:313–9.

    Google Scholar 

  3. Tan Q, Lui PP, Rui YF, Wong YM. Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Eng. 2012;18:840–51.

    CAS  Google Scholar 

  4. Veronesi F, Maglio M, Tschon M, Aldini NN, Fini M. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies. J Biomed Mater Res A. 2014;102:2448–666.

    PubMed  Google Scholar 

  5. Zhu SF, Zhong ZN, Fu XF, et al. Comparison of cell proliferation, apoptosis, cellular morphology and ultrastructure between human umbilical cord and placenta-derived mesenchymal stem cells. Neurosci Lett. 2013;541:77–82.

    CAS  PubMed  Google Scholar 

  6. Yang H, Gao LN, An Y, et al. Comparison of mesenchymal stem cells derived from gingival tissue and periodontal ligament in different incubation conditions. Biomaterials. 2013;34:7033–47.

    CAS  PubMed  Google Scholar 

  7. Radtke CL, Nino-Fong R, Esparza Gonzalez BP, Stryhn H, McDuffee LA. Characterization and osteogenic potential of equine muscle tissue- and periosteal tissue-derived mesenchymal stem cells in comparison with bone marrow- and adipose tissue-derived mesenchymal stem cells. Am J Vet Res. 2013;74:790–800.

    CAS  PubMed  Google Scholar 

  8. Lui PP, Wong OT. Tendon stem cells: experimental and clinical perspectives in tendon and tendon-bone junction repair. Muscles Ligaments Tendons J. 2012;2:163–8.

    PubMed  PubMed Central  Google Scholar 

  9. Hatsushika D, Muneta T, Horie M, et al. Intraarticular injection of synovial stem cells promotes meniscal regeneration in a rabbit massive meniscal defect model. J Orthop Res. 2013;31:1354–9.

    CAS  PubMed  Google Scholar 

  10. 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;8:315–7.

    CAS  PubMed  Google Scholar 

  11. Cihova M, Altanerova V, Altaner C. Stem cell based cancer gene therapy. Mol Pharm. 2011;8:1480–7.

    CAS  PubMed  Google Scholar 

  12. Spaeth E, Klopp A, Dembinski J, Andreeff M, Marini F. Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 2008;15:730–8.

    CAS  PubMed  Google Scholar 

  13. Studeny M, Marini FC, Champlin RE, et al. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res. 2002;62:3603–8.

    CAS  PubMed  Google Scholar 

  14. Beckermann BM, Kallifatidis G, Groth A, et al. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 2008;99:622–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Smith CL, Chaichana KL, Lee YM, et al. Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer. Stem Cells Transl Med. 2015;4:239–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Fakiruddin KS, Baharuddin P, Lim MN, et al. Nucleofection optimization and in vitro anti-tumourigenic effect of TRAIL-expressing human adipose-derived mesenchymal stromal cells. Cancer Cell Int. 2014;14:122.

    PubMed  PubMed Central  Google Scholar 

  17. Coffelt SB, Marini FC, Watson K, et al. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci USA. 2009;106:3806–11.

    CAS  PubMed  Google Scholar 

  18. Lourenco S, Teixeira VH, Kalber T, et al. Macrophage migration inhibitory factor-CXCR4 is the dominant chemotactic axis in human mesenchymal stem cell recruitment to tumors. J Immunol. 2015;194:3463–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Akimoto K, Kimura K, Nagano M, et al. Umbilical cord blood-derived mesenchymal stem cells inhibit, but adipose tissue-derived mesenchymal stem cells promote, glioblastoma multiforme proliferation. Stem Cells Dev. 2013;22:1370–86.

    CAS  PubMed  Google Scholar 

  20. Tian LL, Yue W, Zhu F, Li S, Li W. Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo. J Cell Physiol. 2011;226:1860–7.

    PubMed  Google Scholar 

  21. Powell DW, Adegboyega PA, Di Mari JF, Mifflin RC. Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am J Physiol Gastrointest Liver Physiol. 2005;289:G2–7.

    CAS  PubMed  Google Scholar 

  22. Galiè M, Sorrentino C, Montani M, et al. Mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells. Carcinogenesis. 2005;26:1868–78.

    PubMed  Google Scholar 

  23. Bagley RG, Weber W, Rouleau C, et al. Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers. Int J Oncol. 2009;34:619–27.

    CAS  PubMed  Google Scholar 

  24. Jeon ES, Moon HJ, Lee MJ, et al. Cancer-derived lysophosphatidic acid stimulates differentiation of human mesenchymal stem cells to myofibroblast-like cells. Stem Cells. 2008;26:789–97.

    CAS  PubMed  Google Scholar 

  25. Mishra PJ, Mishra PJ, Humeniuk R, et al. Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res. 2008;68:4331–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Au P, Tam J, Fukumura D, Jain RK. Bone marrow-derived mesenchymal stem cells facilitate engineering of long-lasting functional vasculature. Blood. 2008;111:4551–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Tasso R, Augello A, Carida' M, et al. Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds. Carcinogenesis. 2009;30:150–7.

    CAS  PubMed  Google Scholar 

  28. Qiao L, Xu ZL, Zhao TJ, et al. Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling. Cancer Lett. 2008;269:67–77.

    CAS  PubMed  Google Scholar 

  29. Sun B, Roh KH, Park JR, et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 2009;11:289–98.

    CAS  PubMed  Google Scholar 

  30. Dittmer A, Hohlfeld K, Lützkendorf J, et al. Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10. Cell Mol Life Sci. 2009;66:3053–65.

    CAS  PubMed  Google Scholar 

  31. He N, Kong Y, Lei X, et al. MSCs inhibit tumor progression and enhance radiosensitivity of breast cancer cells by down-regulating Stat3 signaling pathway. Cell Death Dis. 2018;9:1026.

    PubMed  PubMed Central  Google Scholar 

  32. Maestroni GJ, Hertens E, Galli P. Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice. Cell Mol Life Sci. 1999;55:663–7.

    CAS  PubMed  Google Scholar 

  33. François S, Usunier B, Forgue-Lafitte ME, et al. Mesenchymal stem cell administration attenuates colon cancer progression by modulating the immune component within the colorectal tumor microenvironment. Stem Cells Transl Med. 2019;8:285–300.

    PubMed  Google Scholar 

  34. 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:e61366.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhu Y, Sun Z, Han Q, et al. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia. 2009;23:925–33.

    CAS  PubMed  Google Scholar 

  36. Atsuta I, Liu S, Miura Y, et al. Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway. Stem Cell Res Ther. 2013;4:111.

    PubMed  PubMed Central  Google Scholar 

  37. Lu YR, Yuan Y, Wang XJ, et al. The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo. Cancer Biol Ther. 2008;7:245–51.

    CAS  PubMed  Google Scholar 

  38. 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):7728–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Coccè V, Franzè S, Brini AT, et al. In vitro anticancer activity of extracellular vesicles (EVs) secreted by gingival mesenchymal stromal cells primed with paclitaxel. Pharmaceutics. 2019;11(2):E61.

    PubMed  Google Scholar 

  40. Liu J, Han G, Liu H, Qin C. Suppression of cholangiocarcinoma cell growth by human umbilical cord mesenchymal stem cells: a possible role of Wnt and Akt signaling. PLoS ONE. 2013;8:e62844.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Qiao L, Xu Z, Zhao T, et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res. 2008;18:500–7.

    CAS  PubMed  Google Scholar 

  42. Li Y, Zhao Y, Cheng Z, et al. Mesenchymal stem cell-like cells from children foreskin inhibit the growth of SGC-7901 gastric cancer cells. Exp Mol Pathol. 2013;94:430–7.

    CAS  PubMed  Google Scholar 

  43. Zhang T, Lee YW, Rui YF, et al. Bone marrow-derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther. 2013;4:70.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 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;383:13–20.

    CAS  PubMed  Google Scholar 

  45. Martin FT, Dwyer RM, Kelly J, et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat. 2010;124:317–26.

    CAS  PubMed  Google Scholar 

  46. Muehlberg FL, Song YH, Krohn A, et al. Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis. 2009;30:589–97.

    CAS  PubMed  Google Scholar 

  47. Salha S, Gehmert S, Brébant V, et al. PDGF regulated migration of mesenchymal stem cells towards malignancy acts via the PI3K signaling pathway. Clin Hemorheol Microcirc. 2018;70:543–51.

    CAS  PubMed  Google Scholar 

  48. Ishihara S, Inman DR, Li WJ, Ponik SM, Keely PJ. Mechano-signal transduction in mesenchymal stem cells induces prosaposin secretion to drive the proliferation of breast cancer cells. Cancer Res. 2017;77:6179–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Yu JM, Jun ES, Bae YC, Jung JS. Mesenchymal stem cells derived from human adipose tissues favor tumor cell growth in vivo. Stem Cells Dev. 2008;17:463–73.

    CAS  PubMed  Google Scholar 

  50. Meng MY, Li L, Wang WJ, et al. Assessment of tumor promoting effects of amniotic and umbilical cord mesenchymal stem cells in vitro and in vivo. J Cancer Res Clin Oncol. 2019;145:1133–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Luo J, Ok Lee S, Liang L, et al. Infiltrating bone marrow mesenchymal stem cells increase prostate cancer stem cell population and metastatic ability via secreting cytokines to suppress androgen receptor signaling. Oncogene. 2014;33:2768–78.

    CAS  PubMed  Google Scholar 

  52. Lin G, Yang R, Banie L, et al. Effects of transplantation of adipose tissue-derived stem cells on prostate tumor. Prostate. 2010;70:1066–73.

    PubMed  PubMed Central  Google Scholar 

  53. Doğan A, Demirci S, Apdik H, Apdik EA, Şahin F. Dental pulp stem cells (DPSCs) increase prostate cancer cell proliferation and migration under in vitro conditions. Tissue Cell. 2017;49:711–8.

    PubMed  Google Scholar 

  54. Zhu W, Xu W, Jiang R, et al. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 2006;80:267–74.

    CAS  PubMed  Google Scholar 

  55. Mele V, Muraro MG, Calabrese D, et al. Mesenchymal stromal cells induce epithelial-to-mesenchymal transition in human colorectal cancer cells through the expression of surface-bound TGF-β. Int J Cancer. 2014;134:2583–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Sun T, Sun BC, Ni CS, et al. Pilot study on the interaction between B16 melanoma cell-line and bone-marrow derived mesenchymal stem cells. Cancer Lett. 2008;263:35–433.

    CAS  PubMed  Google Scholar 

  57. Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood. 2003;102:3837–44.

    CAS  PubMed  Google Scholar 

  58. Maj M, Kokocha A, Bajek A, Drewa T. The effects of adipose-derived stem cells on CD133-expressing bladder cancer cells. J Cell Biochem. 2019. https://doi.org/10.1002/jcb.28436[Epub ahead of print].

    Article  PubMed  Google Scholar 

  59. Zhong W, Zhu Z, Xu X, et al. Human bone marrow-derived mesenchymal stem cells promote the growth and drug-resistance of diffuse large B-cell lymphoma by secreting IL-6 and elevating IL-17A levels. J Exp Clin Cancer Res. 2019;38(1):73.

    PubMed  PubMed Central  Google Scholar 

  60. Jin J, Wang T, Wang Y, et al. SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43. Int J Oncol. 2017;51:1694–704.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Saito K, Sakaguchi M, Maruyama S, et al. Stromal mesenchymal stem cells facilitate pancreatic cancer progression by regulating specific secretory molecules through mutual cellular interaction. J Cancer. 2018;9(16):2916–29.

    PubMed  PubMed Central  Google Scholar 

  62. Zhou HS, Su XF, Fu XL, et al. Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-β1 induced epithelial-mesenchymal transition. Oncotarget. 2016;7(27):41294–305.

    PubMed  PubMed Central  Google Scholar 

  63. Kabashima-Niibe A, Higuchi H, Takaishi H, et al. Mesenchymal stem cells regulate epithelial-mesenchymal transition and tumor progression of pancreatic cancer cells. Cancer Sci. 2013;104:157–64.

    CAS  PubMed  Google Scholar 

  64. Yan XL, Jia YL, Chen L, et al. Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis. Hepatology. 2013;57:2274–86.

    CAS  PubMed  Google Scholar 

  65. Ma M, Chen S, Liu Z, et al. miRNA-221 of exosomes originating from bone marrow mesenchymal stem cells promotes oncogenic activity in gastric cancer. Onco Targets Ther. 2017;10:4161–71.

    PubMed  PubMed Central  Google Scholar 

  66. He W, Liang B, Wang C, et al. MSC-regulated lncRNA MACC1-AS1 promotes stemness and chemoresistance through fatty acid oxidation in gastric cancer. Oncogene. 2019;38(23):4637–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Chen B, Yu J, Wang Q, et al. Human bone marrow mesenchymal stem cells promote gastric cancer growth via regulating c-Myc. Stem Cells Int. 2018;2018:9501747.

    PubMed  PubMed Central  Google Scholar 

  68. 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):2242–54.

    CAS  PubMed  Google Scholar 

  69. Hall B, Dembinski J, Sasser AK, et al. Mesenchymal stem cells in cancer: tumor-associated fibroblasts and cell-based delivery vehicles. Int J Hematol. 2007;86:8–16.

    CAS  PubMed  Google Scholar 

  70. Dwyer RM, Khan S, Barry FP, et al. Advances in mesenchymal stem cell-mediated gene therapy for cancer. Stem Cell Res Ther. 2010;1:25.

    PubMed  PubMed Central  Google Scholar 

  71. Corsten MF, Shah K. Therapeutic stem-cells for cancer treatment: hopes and hurdles in tactical warfare. Lancet Oncol. 2008;9:376–84.

    PubMed  Google Scholar 

  72. Zhang X, Zhang L, Xu W, et al. Experimental therapy for lung cancer: umbilical cord-derived mesenchymal stem cell-mediated interleukin-24 delivery. Curr Cancer Drug Targets. 2013;13:92–102.

    CAS  PubMed  Google Scholar 

  73. Zhu X, Su D, Xuan S, et al. Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells. Gastric Cancer. 2013;16:155–66.

    CAS  PubMed  Google Scholar 

  74. Dembinski JL, Wilson SM, Spaeth EL, et al. Tumor stroma engraftment of gene-modified mesenchymal stem cells as anti-tumor therapy against ovarian cancer. Cytotherapy. 2013;15:20–322.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Stoff-Khalili MA, Rivera AA, Mathis JM, et al. Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung metastases of breast carcinoma. Breast Cancer Res Treat. 2007;105:157–67.

    PubMed  Google Scholar 

  76. von Einem JC, Guenther C, Volk HD, et al. Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: results from the phase 1/2 TREAT-ME-1 trial. Int J Cancer. 2019;145:1538–46.

    Google Scholar 

  77. Wang X, Chen H, Zeng X, et al. Efficient lung cancer-targeted drug delivery via a nanoparticle/MSC system. Acta Pharm Sin B. 2019;9:167–76.

    PubMed  Google Scholar 

  78. Spano C, Grisendi G, Golinelli G, et al. Soluble TRAIL armed human MSC as gene therapy for pancreatic cancer. Sci Rep. 2019;9:1788.

    PubMed  PubMed Central  Google Scholar 

  79. Lu JH, Peng BY, Chang CC, et al. Tumor-targeted immunotherapy by using primary adipose-derived stem cells and an antigen-specific protein vaccine. Cancers (Basel). 2018;10:E446.

    Google Scholar 

  80. Altanerova U, Babincova M, Babinec P, et al. Human mesenchymal stem cell-derived iron oxide exosomes allow targeted ablation of tumor cells via magnetic hyperthermia. Int J Nanomed. 2017;12:7923–36.

    CAS  Google Scholar 

  81. Tolar J, Nauta AJ, Osborn MJ, et al. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007;25:371–9.

    CAS  PubMed  Google Scholar 

  82. Houghton J, Stoicov C, Nomura S, et al. Gastric cancer originating from bone marrow-derived cells. Science. 2004;306:1568–71.

    CAS  PubMed  Google Scholar 

  83. Compte M, Cuesta AM, Sánchez-Martín D, et al. Tumor immunotherapy using gene-modified human mesenchymal stem cells loaded into synthetic extracellular matrix scaffolds. Stem Cells. 2009;27:753–60.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Health Commission of Weifang (No. wfwsjk_2019_004 to Qing Wang), the National Natural Science Foundation of China (No. 81570945 to Gang Ding), and the Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction (No. KFKT2019013 to Gang Ding).

Author information

Authors and Affiliations

  1. Department of Dentistry, Weifang People’s Hospital, Weifang, 261000, Shandong, People’s Republic of China

    Qing Wang, Ti Li & Wei Wu

  2. Department of Stomatology, Yidu Central Hospital, Weifang Medical University, Linglongshan South Road No. 4138, Qingzhou, 262500, Shandong, People’s Republic of China

    Gang Ding

Authors
  1. Qing Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ti Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gang Ding.

Ethics declarations

Conflict of interest

The authors declare no financial conflicts of interest in association with the present study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Q., Li, T., Wu, W. et al. Interplay between mesenchymal stem cell and tumor and potential application. Human Cell 33, 444–458 (2020). https://doi.org/10.1007/s13577-020-00369-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-020-00369-z

Keywords

Search

Navigation