多发性骨髓瘤患者骨髓间充质干细胞在体外对骨髓瘤细胞趋化迁移的影响
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摘要
目的:探讨体外培养情况下多发性骨髓瘤患者骨髓间充质干细胞(MSC)对骨髓瘤细胞趋化迁移的影响。方法:采用体外培养方法,将骨髓瘤细胞株U266分成两组:A组与正常人骨髓间充质干细胞(N-MSC)共培养,B组与多发性骨髓瘤患者的骨髓间充质干细胞共培养,在有或无硼替佐米作用条件下比较2组U266细胞株的CCR1表达水平、Transwell迁移率以及N-MSC或MM-MSC培养液上清中U266细胞在Transwell中的迁移情况。结果:U266细胞与N-MSC组和MM-MSC共培养后,B组U266细胞在Transwell中的迁移率较高(P<0.05);硼替佐米处理U266细胞后不能消除2组的区别;B组U266细胞的CCR1表达水平高于A组(P<0.05)。骨髓MSC培养上清液实验显示,在无硼替佐米作用条件下,MM-MSC和N-MSC培养上清液与SDF-1相比,具有较强的趋化刺激能力,使细胞在Transwell中的迁移率增高,而在有硼替佐米作用下,3组培养上清液使细胞在Transwell中迁移率降低(P<0.05),但不管是否在硼替佐米作用下,MM-MSC和N-MSC培养上清液对U266细胞在Transw ell中的迁移作用无显著性影响(P>0.05)。结论:骨髓瘤患者的骨髓间充质干细胞本身有部分内在缺陷,通过与骨髓瘤细胞直接相互作用而影响其体外趋化功能。
Objective: To explore the effect of bone marrow mesenchymal stem cells( MSC) in patients with multiple myeloma( MM) on chemotactic migration of myeloma cells in vitro. Methods: By in vitro co-culture with diffferent MSC, the myeloma cell U266 was divided into 2 groups: group A in which the U266 cells were co-cultured with normal person MSC( N-MSC) and group B in which the U266 cells were co-cultured with MM-MSC. The expression level of CCRI in U266 cells, migration rate of U266 cells in Transwell, and the effect of supernantant from co-culture of U266 cells with N-MSC and MM-MSC on the migration in Transwell were compared in condition with or without bortezomib. Results: After co-culture of U266 cells with N-MSC or MM-MSC, the migration rate of U266 cells in Transwell in B group was higher than that in A group( P < 0. 05). The difference between 2 groups could not be eliminated after treatment of U266 cells with bortezomib. The CCR1 expression level of U266 cells in B group was higher than that in A group( P <0. 05). The culture supernatant of bone marrow MSC showed that in condition without bortezomib the culture supernatant of MSC in MM patients and normal persons both possessed more strong chemotactic ability and enhanced the migration rate of cells in Transwell, compared with SDF-4, meanswhile the culture supernatant in 3 groups reduced the migration rate of cells in condition with bortezomib( P < 0. 05), but there were no statistical difference in migration rate of U266 cells in Transwell between supernatant of N-MSC and MM-MSC culture( P >0. 05), no matter the bortezonib was used or not. Conclusion: The bone marrow MSC in MM patients have same intrinsic defects that affect the chemotaxis of cells in vitro by directly interacting with myeloma cells.
Objective: To explore the effect of bone marrow mesenchymal stem cells( MSC) in patients with multiple myeloma( MM) on chemotactic migration of myeloma cells in vitro. Methods: By in vitro co-culture with diffferent MSC, the myeloma cell U266 was divided into 2 groups: group A in which the U266 cells were co-cultured with normal person MSC( N-MSC) and group B in which the U266 cells were co-cultured with MM-MSC. The expression level of CCRI in U266 cells, migration rate of U266 cells in Transwell, and the effect of supernantant from co-culture of U266 cells with N-MSC and MM-MSC on the migration in Transwell were compared in condition with or without bortezomib. Results: After co-culture of U266 cells with N-MSC or MM-MSC, the migration rate of U266 cells in Transwell in B group was higher than that in A group( P < 0. 05). The difference between 2 groups could not be eliminated after treatment of U266 cells with bortezomib. The CCR1 expression level of U266 cells in B group was higher than that in A group( P <0. 05). The culture supernatant of bone marrow MSC showed that in condition without bortezomib the culture supernatant of MSC in MM patients and normal persons both possessed more strong chemotactic ability and enhanced the migration rate of cells in Transwell, compared with SDF-4, meanswhile the culture supernatant in 3 groups reduced the migration rate of cells in condition with bortezomib( P < 0. 05), but there were no statistical difference in migration rate of U266 cells in Transwell between supernatant of N-MSC and MM-MSC culture( P >0. 05), no matter the bortezonib was used or not. Conclusion: The bone marrow MSC in MM patients have same intrinsic defects that affect the chemotaxis of cells in vitro by directly interacting with myeloma cells.
引文
1李香丽,张小影,臧立,等.骨髓间充质干细胞在多发性骨髓瘤活动与缓解期具有不同的促血管生成能力.中国组织工程研究,2014;18(37):5935-5941.
2 Bigildeev AE,Zezina EA,Drize NJ.The effects of interleukin-1 beta and gamma-quantum braking radiation on mesenchymal progenitor cells.Mol Biol(Mosk),2017;51(3):447-459.
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4 张晓慧,孙谕,王子妍,等.骨髓间充质干细胞与多发性骨髓瘤细胞共培养后CX43表达及SDF-1α分泌水平的变化及其意义.中华血液学杂志,2013;34(9):788-793.
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6 Sung HT,Sigerson L,Cheng C.Social capital accumulation in location-based mobile game playing:a multiple-process approach.Cyberpsychol Behav Soc Netw,2017;20(8):486-493.
7 费小明,李俊霞,汤郁,等.骨髓瘤患者骨髓间充质干细胞可异常影响骨髓瘤细胞株的趋化功能.中国组织工程研究,2015;(50):8037-8042.
8 Sekino M,Funaoka H,Sato S,et al.Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock:A preliminary study.J Crit Care,2017;42:92-100.
9 张艳丽,傅晋翔,张宏,等.骨髓间充质干细胞对多发性骨髓瘤细胞迁移和归巢特性的影响.中国实验血液学杂志,2016,24(2):469-473.
10 Barhanpurkar-Naik A,Mhaske ST,Pote ST,et al.Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4.Stem Cell Res Ther.2017;8(1):168.
11 李军,李炳宗,陈萍,等.硼替佐米对多发性骨髓瘤患者间充质干细胞自噬活性和成骨分化潜能的影响.中华内科杂志,2012;51(2):140-142.
12 Yang M,Arai A,Udagawa N,et al.Osteogenic factor runx2 marks a subset of leptin receptor-positive cells that sit atop the bone marrow stromal cell hierarchy.Sci Rep,2017;7(1):4928.
13 武海军,银和平,胡继平,等.非接触共培养条件下骨髓间充质干细胞向类髓核细胞的诱导分化.中国组织工程研究,2016;20(45):6706-6713.
14 王路,张翼鷟.伴髓外病变的多发性骨髓瘤研究进展.中国实验血液学杂志,2016;24(3):945-948.
15 Hobday M,Chow K,Meuleners L,et al.Identification of high risk metropolitan intersection sites in perth,Australia.Accid Anal Prev,2017;106:336-340.
2 Bigildeev AE,Zezina EA,Drize NJ.The effects of interleukin-1 beta and gamma-quantum braking radiation on mesenchymal progenitor cells.Mol Biol(Mosk),2017;51(3):447-459.
3 Neethirajan S,Tuteja SK,Huang ST,et al.Recent advancement in biosensors technology for animal and livestock health management.Biosens Bioelectron,2017;98:398-407.
4 张晓慧,孙谕,王子妍,等.骨髓间充质干细胞与多发性骨髓瘤细胞共培养后CX43表达及SDF-1α分泌水平的变化及其意义.中华血液学杂志,2013;34(9):788-793.
5 Triberti S,Durosini I,Aschieri F,et al.The influence of social and contextual expectations on digital rendition of identity.Cyberpsychol Behav Soc Netw,2017;20(8):501-507.
6 Sung HT,Sigerson L,Cheng C.Social capital accumulation in location-based mobile game playing:a multiple-process approach.Cyberpsychol Behav Soc Netw,2017;20(8):486-493.
7 费小明,李俊霞,汤郁,等.骨髓瘤患者骨髓间充质干细胞可异常影响骨髓瘤细胞株的趋化功能.中国组织工程研究,2015;(50):8037-8042.
8 Sekino M,Funaoka H,Sato S,et al.Intestinal fatty acid-binding protein level as a predictor of 28-day mortality and bowel ischemia in patients with septic shock:A preliminary study.J Crit Care,2017;42:92-100.
9 张艳丽,傅晋翔,张宏,等.骨髓间充质干细胞对多发性骨髓瘤细胞迁移和归巢特性的影响.中国实验血液学杂志,2016,24(2):469-473.
10 Barhanpurkar-Naik A,Mhaske ST,Pote ST,et al.Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4.Stem Cell Res Ther.2017;8(1):168.
11 李军,李炳宗,陈萍,等.硼替佐米对多发性骨髓瘤患者间充质干细胞自噬活性和成骨分化潜能的影响.中华内科杂志,2012;51(2):140-142.
12 Yang M,Arai A,Udagawa N,et al.Osteogenic factor runx2 marks a subset of leptin receptor-positive cells that sit atop the bone marrow stromal cell hierarchy.Sci Rep,2017;7(1):4928.
13 武海军,银和平,胡继平,等.非接触共培养条件下骨髓间充质干细胞向类髓核细胞的诱导分化.中国组织工程研究,2016;20(45):6706-6713.
14 王路,张翼鷟.伴髓外病变的多发性骨髓瘤研究进展.中国实验血液学杂志,2016;24(3):945-948.
15 Hobday M,Chow K,Meuleners L,et al.Identification of high risk metropolitan intersection sites in perth,Australia.Accid Anal Prev,2017;106:336-340.