OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press765BASIC RESEARCHФУНДАМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ В ПРАКТИЧЕСКОЙ МЕДИЦИНЕ НА СОВРЕМЕННОМ ЭТАПЕInfluence of allogeneic mesenchymal stem cells on leukemic cells in vitro sensitivity to antileukemic drugsВлияние аллогенных мезенхимальных стволовых клеток на чувствительность лейкемических клеток к противолейкемическим препаратам in vitroTatarinovaO. S.ТатариноваО. С.
Russian Federation

Moscow

ФГУ Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии

Москва

OsipovaE. Yu.ОсиповаЕ. Ю.
Russian Federation

Moscow

Елена Юрьевна Осипова

ФГУ Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии

Москва

e_ossipova@mail.ruRumyantsevS. A.РумянцевС. А.
Russian Federation

Moscow

ФГУ Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии

Москва

Federal Research Center of Pediatric Hematology, Oncology and ImmunologyРосздрав271120104333827112022271120222010https://oncohematology.abvpress.ru/ongm/article/view/765

   In present study influence of allogeneic bone marrow mesenchymal stem cells (MSC) on patients’ leukemic cells is investigated. Influence on in vitro sensitivity to antileukemic drugs and spontaneous and cytarabine-induced apoptosis of leukemic cells was studied. It has`been shown that MSC reduce myeloid leukemic cells sensitivity to daunorubicine. However, MSC did not statistically significant influence on spontaneous and cytarabine-induced apoptosis of leukemic cells.

   В настоящем исследовании изучено влияние аллогенных мезенхимальных стволовых клеток (МСК) костного мозга доноров на лейкемические клетки пациентов. В ходе работы исследовались действие на чувствительность к противолейкемическим препаратам in vitro и способность лейкемических клеток к спонтанному и индуцированному цитарабином апоптозу. Было показано, что МСК снижают чувствительность лейкемических клеток миелоидного ряда к даунорубицину. Однако МСК не оказывали статистически значимого влияния на уровни спонтанного и индуцированного цитарабином апоптоза лейкемических клеток.

mesenchymal stem cellsantileukemic drug sensitivityleukemic cellsspontaneous apoptosiscytarabine-induced apoptosisмезенхимальные стволовые клеткичувствительность к противолейкемическим препаратамлейкемические клеткиспонтанный апоптозиндуцированный цитарабином апоптоз1. Haynesworth S. E., Baber M. A., Caplan A. I. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996; 166: 585–92.Haynesworth S. E., Baber M. A., Caplan A. I. Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996; 166: 585–92.2. Cheng L., Qasba P., Vanguri P., Thiede M. A. Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34+ hematopoietic progenitor cells. J Cell Physiol 2000; 184: 58–69.Cheng L., Qasba P., Vanguri P., Thiede M. A. Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34+ hematopoietic progenitor cells. J Cell Physiol 2000; 184: 58–69.3. Le Blanc K., Rasmusson I., Sundberg B., Götherström C., Hassan M., Uzunel M., Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439–41.Le Blanc K., Rasmusson I., Sundberg B., Götherström C., Hassan M., Uzunel M., Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439–41.4. Rasmusson I., Ringden O., Sundberg B., Le Blanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76: 1208–13.Rasmusson I., Ringden O., Sundberg B., Le Blanc K. Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transplantation 2003; 76: 1208–13.5. Le Blanc K., Rasmusson I., Götherström C., Seidel C., Sundberg B., Sundin M., Rosendahl K., Tammik C., Ringdén O. Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes. Scand J Immunol 2004; 60: 307–15.Le Blanc K., Rasmusson I., Götherström C., Seidel C., Sundberg B., Sundin M., Rosendahl K., Tammik C., Ringdén O. Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes. Scand J Immunol 2004; 60: 307–15.6. Liang R., Huang G. S., Chen X. Q., Wang Z., Feng J. L., Zhang W. P., Guo Y., Yang G. Y. Effects of human fibroblastoid stromal cell line on proliferation of HL-60 cells and expression of VEGF. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2003; 11 (5): 476–9.Liang R., Huang G. S., Chen X. Q., Wang Z., Feng J. L., Zhang W. P., Guo Y., Yang G. Y. Effects of human fibroblastoid stromal cell line on proliferation of HL-60 cells and expression of VEGF. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2003; 11 (5): 476–9.7. Lin Y. M., Bu L. M., Yang S. J., Gao S., Zhang G. Z. Influence of human mesenchymal stem cells on cell proliferation and chemosensitivity of K562 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006; 14 (2): 308–12.Lin Y. M., Bu L. M., Yang S. J., Gao S., Zhang G. Z. Influence of human mesenchymal stem cells on cell proliferation and chemosensitivity of K562 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006; 14 (2): 308–12.8. Lin Y. M., Zhang G. Z., Leng Z. X., Lu Z. X., Bu L. S., Gao S., Yang S. J. Study on the bone marrow mesenchymal stem cells induced drug resistance in the U937 cells and its mechanism. Chin Med J (Engl) 2006; 119 (11): 905–10.Lin Y. M., Zhang G. Z., Leng Z. X., Lu Z. X., Bu L. S., Gao S., Yang S. J. Study on the bone marrow mesenchymal stem cells induced drug resistance in the U937 cells and its mechanism. Chin Med J (Engl) 2006; 119 (11): 905–10.9. Liang R., Huang G. S., Wang Z., Chen X. Q., Bai Q. X., Zhang Y. Q., Dong B. X., Wang W. Q. Effects of human bone marrow stromal cell line (HFCL) on the proliferation, differentiation and apoptosis of acute myeloid leukemia cell lines U937, HL-60 and HL-60/VCR. Int J Hematol 2008; 87 (2): 152–66.Liang R., Huang G. S., Wang Z., Chen X. Q., Bai Q. X., Zhang Y. Q., Dong B. X., Wang W. Q. Effects of human bone marrow stromal cell line (HFCL) on the proliferation, differentiation and apoptosis of acute myeloid leukemia cell lines U937, HL-60 and HL-60/VCR. Int J Hematol 2008; 87 (2): 152–66.10. Zhu Y., Sun Z., Han Q., Liao L., Wang J., Bian C., Li J., Yan X., Liu Y., Shao C., Zhao R. C. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia 2009. Jan 15. doi: 10.1038/leu.2008.384.Zhu Y., Sun Z., Han Q., Liao L., Wang J., Bian C., Li J., Yan X., Liu Y., Shao C., Zhao R. C. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia 2009. Jan 15. doi: 10.1038/leu.2008.384.11. Ding Y., Lu H., Lu S. F., Lu R. N., Liu P., Wu Y. J., Li J. Y. Effects of human bone marrow mesenchymal stem cells on proliferation and apoptosis of k562 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2009; 17 (1): 137–40.Ding Y., Lu H., Lu S. F., Lu R. N., Liu P., Wu Y. J., Li J. Y. Effects of human bone marrow mesenchymal stem cells on proliferation and apoptosis of k562 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2009; 17 (1): 137–40.12. Manabe A., Coustan-Smith E., Behm F. G., Raimondi S. C., Campana D. Bone marrow-derived stromal cells prevent apoptotic cell death in B-lineage acute lymphoblastic leukemia. Blood 1992; 79 (9): 2370–7.Manabe A., Coustan-Smith E., Behm F. G., Raimondi S. C., Campana D. Bone marrow-derived stromal cells prevent apoptotic cell death in B-lineage acute lymphoblastic leukemia. Blood 1992; 79 (9): 2370–7.13. Konopleva M., Konoplev S., Hu W., Zaritskey A. Y., Afanasiev B. V., Andreeff M. Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia 2002; 16 (9): 1713–24.Konopleva M., Konoplev S., Hu W., Zaritskey A. Y., Afanasiev B. V., Andreeff M. Stromal cells prevent apoptosis of AML cells by up-regulation of anti-apoptotic proteins. Leukemia 2002; 16 (9): 1713–24.14. Mudry R. E., Fortney J. E., York T., Hall B. M., Gibson L. F. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood 2000; 96 (5): 1926–32.Mudry R. E., Fortney J. E., York T., Hall B. M., Gibson L. F. Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy. Blood 2000; 96 (5): 1926–32.15. Garrido S. M., Appelbaum F. R., Willman C. L., Banker D. E. Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5). Exp Hematol 2001; 29 (4): 448–57.Garrido S. M., Appelbaum F. R., Willman C. L., Banker D. E. Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5). Exp Hematol 2001; 29 (4): 448–57.16. Fortney J. E., Zhao W., Wenger S. L., Gibson L. F. Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy. Leuk Res 2001; 25 (10): 901–7.Fortney J. E., Zhao W., Wenger S. L., Gibson L. F. Bone marrow stromal cells regulate caspase 3 activity in leukemic cells during chemotherapy. Leuk Res 2001; 25 (10): 901–7.17. Wang L., Fortney J. E., Gibson L. F. Stromal cell protection of B-lineage acute lymphoblastic leukemic cells during chemotherapy requires active Akt. Leuk Res 2004; 28 (7): 733–42.Wang L., Fortney J. E., Gibson L. F. Stromal cell protection of B-lineage acute lymphoblastic leukemic cells during chemotherapy requires active Akt. Leuk Res 2004; 28 (7): 733–42.18. Астрелина Т. А. Клиническое значение чувствительности лейкемических клеток к химиотерапии при остром лимфобластном лейкозе у детей по результатам МТТ-теста ex vivo / Т. А. Астрелина [и др.] // Гематол. и трансфузиол. – 2002. – 6: 21–4.Астрелина Т. А. Клиническое значение чувствительности лейкемических клеток к химиотерапии при остром лимфобластном лейкозе у детей по результатам МТТ-теста ex vivo / Т. А. Астрелина [и др.] // Гематол. и трансфузиол. – 2002. – 6: 21–4.19. Hongo T., Shuhei Yajima, Minoru Sakurai, Yasuo Horikoshi and Ryoji. In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia. Blood 1997; 89 (8): 2959–65.Hongo T., Shuhei Yajima, Minoru Sakurai, Yasuo Horikoshi and Ryoji. In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia. Blood 1997; 89 (8): 2959–65.20. Janka-Schaub G. E., Harms D. O., den Boer M. L., Veerman A. J., Pieters R. In vitro drug resistance as independent prognostic factor in the study COALL-O5-92 Treatment of childhood acute lymphoblastic leukemia; two-tiered classification of treatments based on accepted risk criteria and drug sensitivity profiles in study COALL-06-97. Klin Padiatr 1999; 211 (4): 233–8.Janka-Schaub G. E., Harms D. O., den Boer M. L., Veerman A. J., Pieters R. In vitro drug resistance as independent prognostic factor in the study COALL-O5-92 Treatment of childhood acute lymphoblastic leukemia; two-tiered classification of treatments based on accepted risk criteria and drug sensitivity profiles in study COALL-06-97. Klin Padiatr 1999; 211 (4): 233–8.21. Kaspers G. J. L., Veerman A. J. P., Piters R., Van Zantwijk C. H., Smets L. A., Van Wering E. R., Van Der Does-Van Den Berg A. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 1997; 90: 2723–9.Kaspers G. J. L., Veerman A. J. P., Piters R., Van Zantwijk C. H., Smets L. A., Van Wering E. R., Van Der Does-Van Den Berg A. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 1997; 90: 2723–9.22. Veerman A. J. P., Pieters R. Drug sensitivity assaya in leukemia and lymphoma. Br J Haemotol 1990; 74: 381–4.Veerman A. J. P., Pieters R. Drug sensitivity assaya in leukemia and lymphoma. Br J Haemotol 1990; 74: 381–4.