The study of migration of the multipotent mesenchymal stromal cells in the body of animal with a tumor

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The study of stem and progenitor cells role in carcinogenesis is the subject of intense investigation. At the same time fluorescent methods become more common for the studying of the stem cells migration into recipient organism and their involvement in tumor pathogenesis. In this study the interaction between bone marrow multipotent mesenchymal stromal cells (MMSC) and allogenic tumor (Lewis lung carcinoma) was investigated using the methods of the flow cytometry and a confocal laser scanning microscopy. MMSC were isolated from bone marrow of the males GFP+-transgenic mice C57/Bl6. The tumors were implanted in mice C57/Bl6 by subcutaneous injection of Lewis lung carcinoma tumor cells. The day before that myeloablation was performed by irradiation. GFP+-MMSC and bone marrow cells from the males C57/Bl6 were administrated into mice C57/Bl6 systemically on the following day after irradiation. The animals were divided into two groups: 1 — irradiated mice with tumor inoculation and injection of bone marrow cells including GFP+-MMSC; 2 (control) — unirradiated mice with tumor inoculation but without cells transplantation. The fluorescence level of freshly isolated bone marrow cells from animals of the first and control groups was evaluated by flow cytometry on the 7, 12 and 15 days after GFP+-MMSC transplantation. In these groups of animals we analyzed the distribution of the labeled GFP+-MMSC and their descendants in the organs and tumor tissues by laser scanning microscopy also on the 7, 12 and 15 days after transplantation. It was established that in systemic administration donor GFP+-MMSC were absent in the bone marrow and tissues of induced tumors, but at the same time they were able to migrate into recipients accumulating in the potential niches (spleen, liver) and proliferate actively.

Full Text

Restricted Access

About the authors

A. V Meleshina

Nizhny Novgorod State University, Nizhny Novgorod

E. I Cherkasov

Nizhny Novgorod State University, Nizhny Novgorod

E. A Sergeeva

Institute of Applied Physics of Russian Academy of Science, Nizhny Novgorod

M. V Shirmanova

Nizhny Novgorod State Medical Academy, Nizhny Novgorod

I. V Balalaeva

Institute of Applied Physics of Russian Academy of Science, Nizhny Novgorod

E. V Kiseleva

N.K. Koltzov Institute of Developmental Biology of RAS, Moscow

E. V Zayganova

Nizhny Novgorod State Medical Academy, Nizhny Novgorod

References

  1. Nolan D.J., Ciarrocchi A., Mellick A. S. Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization. Gen. Dev. 2007; 21:1546-58.
  2. Shen J., Tsai Y.-T., DiMarco N.M. Transplantation of mesenchymal stem cells from young donors delays aging in mice. Scientific reports 2011; 67 (1):1 —7.
  3. Генин А.М., Капланский А.С. Биоэтические правила проведения исследований на человеке и животных в авиационной, космической и морской медицине. Авиационная и экологическая медицина 2001; 4:14-20.
  4. Evrogen Joint Stock Company. Basic fluorescent proteins, http://www.evrogen.ru/products/TagGFP2/TagGFP2.shtml.
  5. Мелешина А.В., Черкасова Е.И., Сергеева Е.А. Исследование взаимодействия мезенхимных стволовых клеток и опухоли методами флюоресцентного биоимиджинга. Современные технологии в медицине 2012; 4:7-16.
  6. Wolf D., Rumpold H., Koeck R. Mesenchymal stem cells: potential precursors for tumor stroma and targeted delivery vehicles for anticancer agents. J. Nation. Cancer Inst. 2005; 97t7):540-2.
  7. Bell E.L., Klimova T.A., Eisenbart J. Mitochondrial reactive oxygen species trigger hypoxia inducible factor dependent extension of the replicative life span during hypoxia. Mol. Cell Biol. 2007; 27:5737-45.
  8. Wang H., Cao F., De A. Trafficking mesenchymal stem cell engraftment and differentiation in tumor-bearing mice by bioluminescence imaging. Stem cells 2009; 27:1548-58.
  9. Spaeth E. L., Dembinski L., Sasser A.K. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. Plos One 2009; 4:1-11.
  10. Kidd S., Spaeth E., Dembinski J. L. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 2009; 27:2614-23
  11. Cheng L., Hammond H., Ye Z. Human adult marrow cells support prolonged expansion of human embryonic stem cells in culture. Stem Cells 2003; 21(2):131-42.
  12. Пыко И.В., Корень С.В., Квачева З.Б. Мезенхимальные стволовые клетки костного мозга: свойства, функции, возможность использования в регенеративной и восстановительной терапии. Мед. Журн. 2007; 4:18-22.
  13. Ren C., Kumar S., Chanda D. Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model. Stem Cells 2008; 26:2332-8.
  14. Komarova S., Kawakami Y., Stoff-Khalili M.A. Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol. Cancer Ther. 2006; 5:755-66.
  15. Karnoub A.E., Dash A.B., Vo A.P. Mesenchymal stem cells within tumor stroma promote breast cancer metastasis. Nature 2007; 449:557-63.
  16. Niess H., Bao Q., Conrad C. Selective targeting of genetically engineered mesenchymal stem cells to tumor stroma microenvironments using tissuespecific suicide gene expression suppresses growth of hepatocellular carcinoma. Ann. Surg. 2011; 254:767-74.
  17. Cuiffo B.G., Karnoub A.E. Mesenchymal stem cells in tumor development. Emerging roles and concepts. Cell Adhes. Migrat. 2012; 6(3):220-30.
  18. Furia L., Cicalese A., Rancati I. et al. Stem Cell Biology in Cancer Research. A New Challenge for Fluorescence Microscopy, http://www. leica-microsystems.com/science-lab/stem-cell-biology-in-cancer-research/.
  19. Hogan C., Dupre-Crochet S., Norman M. Characterization of the interface between normal and transformed epithelial cells. Nat. Cell Biol. 2009; 11(4):460-7.
  20. Saton A., Saito T., Sato Y. et al. Traffic of infused bone marrow cells after genetically labeled syngeneic bone marrow transplantation following lethal irradiation in mice. Fukushima J. Med. Sci. 2008; 54(1):11-24.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2013 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: 

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies