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Umezu T, Imanishi S, Azuma K, et al. Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis. Blood Adv. 2017;1(13):812-823doi: 10.1182/bloodadvances.2016003251.
Umezu, T., Imanishi, S., Azuma, K., Kobayashi, C., Yoshizawa, S., Ohyashiki, K., & Ohyashiki, J. H. (2017). Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis. Blood advances, 1(13), 812-823. https://doi.org/10.1182/bloodadvances.2016003251
Umezu, Tomohiro, et al. "Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis." Blood advances vol. 1,13 (2017): 812-823. doi: https://doi.org/10.1182/bloodadvances.2016003251
Umezu T, Imanishi S, Azuma K, Kobayashi C, Yoshizawa S, Ohyashiki K, Ohyashiki JH. Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis. Blood Adv. 2017 May 16;1(13):812-823. doi: 10.1182/bloodadvances.2016003251. eCollection 2017 May 23. PMID: 29296725; PMCID: PMC5727805.
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Blood Adv. 2017 May 16;1(13):812-823. doi: 10.1182/bloodadvances.2016003251. eCollection 2017 May 23.

Replenishing exosomes from older bone marrow stromal cells with miR-340 inhibits myeloma-related angiogenesis.

Blood advances

Tomohiro Umezu, Satoshi Imanishi, Kenko Azuma, Chiaki Kobayashi, Seiichiro Yoshizawa, Kazuma Ohyashiki, Junko H Ohyashiki

Affiliations

  1. Department of Hematology and.
  2. Department of Molecular Oncology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.

PMID: 29296725 PMCID: PMC5727805 DOI: 10.1182/bloodadvances.2016003251

Abstract

The study of bone marrow stromal cells (BMSCs) and the exosomes they secrete is considered promising for cancer therapy. However, little is known about the effect of donor age on BMSCs. In the present study, we investigated the therapeutic potential of BMSC exosomes derived from donors of different ages using an in vivo model of hypoxic bone marrow in multiple myeloma (MM). We found that donor age was strongly related to senescent changes in BMSCs. Exosomes derived from young BMSCs significantly inhibited MM-induced angiogenesis in Matrigel plugs. The exosomal microRNA (miRNA) expression profile was different between young and older BMSCs, despite similarities in the size and quantity of exosomes. Of note was the observation that the antiangiogenic effect of older BMSCs was enhanced by direct transfection of miR-340 that was preferentially expressed in exosomes derived from young BMSCs. We found that miR-340 inhibited angiogenesis via the hepatocyte growth factor/c-MET (HGF/c-MET) signaling pathway in endothelial cells. Our data provide new insights into exosome-based cancer therapy by modification of BMSC-derived exosomes.

Conflict of interest statement

Conflict of interest disclosure: K.O. received research support from Celgene KK, Chugai Pharmaceutical KK, and Janssen Pharma KK. The remaining authors declare no competing financial interests.

References

  1. J Clin Invest. 2013 Apr;123(4):1542-55 - PubMed
  2. Sci Rep. 2015 Nov 19;5:16765 - PubMed
  3. J Biol Chem. 2010 Jul 2;285(27):20532-40 - PubMed
  4. N Engl J Med. 2011 Mar 17;364(11):1046-60 - PubMed
  5. Nat Med. 2013 Nov;19(11):1423-37 - PubMed
  6. Cell. 2008 Feb 22;132(4):681-96 - PubMed
  7. Stem Cells Dev. 2013 Mar 1;22(5):772-80 - PubMed
  8. Leukemia. 2001 Dec;15(12):1950-61 - PubMed
  9. J Biol Chem. 2013 Nov 29;288(48):34343-51 - PubMed
  10. Regen Med. 2011 Jul;6(4):481-92 - PubMed
  11. Nat Cell Biol. 2007 Jun;9(6):654-9 - PubMed
  12. Blood. 2008 Mar 15;111(6):2962-72 - PubMed
  13. Acta Pharm Sin B. 2016 Jul;6(4):287-96 - PubMed
  14. Stem Cells. 2014 Jan;32(1):116-25 - PubMed
  15. Am J Cancer Res. 2011;1(1):98-110 - PubMed
  16. Blood. 2014 Dec 11;124(25):3748-57 - PubMed
  17. Leukemia. 2014 Apr;28(4):970-3 - PubMed
  18. Nat Biotechnol. 2011 Apr;29(4):341-5 - PubMed
  19. Oncogene. 2013 May 30;32(22):2747-55 - PubMed
  20. J Biol Chem. 2010 Jun 4;285(23):17442-52 - PubMed
  21. J Biomed Biotechnol. 2012;2012:157496 - PubMed
  22. Nat Rev Immunol. 2009 Jan;9(1):57-62 - PubMed
  23. Stem Cell Res Ther. 2014 Jun 10;5(3):76 - PubMed
  24. Cytotherapy. 2009;11(5):503-15 - PubMed
  25. PLoS One. 2013;8(3):e59756 - PubMed
  26. Clin Cancer Res. 2014 Nov 15;20(22):5796-807 - PubMed
  27. Biochim Biophys Acta. 2012 Jul;1820(7):940-8 - PubMed
  28. Transpl Immunol. 2014 May;30(4):122-7 - PubMed
  29. Cell Biol Int. 2012 Aug 1;36(8):747-53 - PubMed
  30. BMC Med. 2013 Jun 11;11:146 - PubMed
  31. Clin Cancer Res. 2013 Aug 15;19(16):4371-82 - PubMed
  32. ISRN Biochem. 2014 Apr 10;2014:351959 - PubMed
  33. Cancer. 2011 Jul 1;117(13):2842-52 - PubMed
  34. Pharmaceuticals (Basel). 2013;6(5):659-80 - PubMed
  35. Antioxid Redox Signal. 2014 Nov 1;21(13):1905-15 - PubMed
  36. PLoS One. 2012;7(9):e44092 - PubMed
  37. J Biol Chem. 2012 Jan 6;287(2):1397-405 - PubMed
  38. Nucleic Acids Res. 2011 Jan;39(Database issue):D163-9 - PubMed
  39. BMC Med. 2015 Mar 05;13:45 - PubMed

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