骨髓间充质干细胞对白血病细胞生长影响的研究
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摘要
目的
比较K562细胞与相同数量以及不同数量的人骨髓间充质干细胞(MSCs)粘附培养前后K562细胞增殖、细胞周期和凋亡的变化,以研究骨髓间充质干细胞对人白血病K562细胞生长的影响。
方法
通过建立正常人骨髓间充质干细胞的体外培养体系及其与K562细胞共培养的体系测定K562细胞的生长曲线;将不同数量的MSCs与K562细胞共培养测定K562细胞的增殖率曲线;流式细胞仪检测K562细胞周期以及凋亡的变化。
结果
与单独K562细胞培养相比,与相同数量MSCs共培养后,K562细胞生长受抑;与不同数量MSCs共培养后,其对K562细胞的抗增殖作用呈剂量依赖性;细胞周期分析发现K562细胞与MSCs共培养后,G0/G1期以及G2/M期的细胞增加, S期的细胞减少。共培养24 h、48 h、72 h后用流式细胞仪检测其凋亡率,发现K562细胞的凋亡率下降。
结论
正常人骨髓间充质干细胞能导致K562细胞生长抑制,阻止K562细胞周期的运行,凋亡率下降,且在一定范围内,随着间充质干细胞数量的增加其对K562细胞的抗增殖作用增强。
目的
观察骨髓间充质干细胞(BMMSC)对小鼠急性淋巴细胞白血病(ALL)模型中白血病细胞的作用;
方法
将携带绿色荧光蛋白(eGFP)基因标记的P388细胞(小鼠急性淋巴细胞白血病细胞系)腹腔接种于DBA/2小鼠建立ALL小鼠动物模型,静脉输注体外培养的骨髓间充质干细胞。记录小鼠存活时间;监测小鼠血常规;流式细胞仪检测组织器官标本中的eGFP+细胞的百分比;观察各小鼠脏器发生的病理学变化以及检测输注MSC的小鼠体内Y染色体的存在。
结果
骨髓间充质干细胞能延长ALL小鼠的生存时间,但其血常规变化不大; MSCs能够减少各组织白血病细胞的浸润,并具有向各组织定植的能力。
结论
骨髓间充质干细胞能影响小鼠急性淋巴细胞白血病(ALL)模型中白血病细胞的生长。
Objective To compare K562 cell proliferation, cell cycle and apoptosis before and after adhesive culture with MSCs of the same and the different counts.,so as to study the effect of human bone marrow mesenchymal stem cells (MSCs) on the growth of K562 cells.
Methods Culture system of bone marrow MSCs and co-culture system of K562 cells and BMSCs in vitro were established. And K562 cell proliferation curves were drawn. K562 cells were co-cultured with different counts of BMSCs and their growth curves were shown. Cell cycle and apoptosis were determined by flow cytometry.
Results The proliferation of K562 cells cultured with the same amounts of MSCs was inhibited. When co-cultured with the different amounts of MSCs cells, MSCs exhibited a dose-dependent anti-proliferation effect on K562 cells. The percentages of G0/G1 and G2/M phase of K562 cells co-cultured with MSCs were higher than those of the control while the percentage of S phase cells was lower.
Conclusions The normal bone marrow mesenchymal stem cells can inhibit the proliferation, progress of cell cycle and the rate of apoptosis of K562 cells. As the number of mesenchymal stem cells increased, their anti-proliferation effect on the K562 cells was enhanced in a certain range.
Objective To observe the effect of bone marrow mesenchymal stem cell(sBMMSCs)on leukemic cells of acute lymphocytic leukemia model.
Methods The model of acute lymphocytic leukemia was established by using P388 cell line expressing enhanced green flourescent protein (eGFP) to inoculate in the abdominal cavities of DBA/2 mice.And then the models were intravenously infused BMMSCs which were cultured in vitro.The control groups were injected with P388 cell line or sodium chloride alone. The percentages of eGFP+ cells of samples were evaluated by flow cytometry, the survial time was recorded,blood routine of mice was monitored, the pathological changes of organs was observed and the exist of Y chromosomal was detected.
Results BMMSCs could decrease the infiltration of leukemic cells in the tissues of ALL mice, increase the survival time of mice and have the ability of orientation planting. But blood routine was not changed obviously.
Conclusions BMMSCs can affect the growth of leukemic cells in acute lymphocytic leukemia model.
比较K562细胞与相同数量以及不同数量的人骨髓间充质干细胞(MSCs)粘附培养前后K562细胞增殖、细胞周期和凋亡的变化,以研究骨髓间充质干细胞对人白血病K562细胞生长的影响。
方法
通过建立正常人骨髓间充质干细胞的体外培养体系及其与K562细胞共培养的体系测定K562细胞的生长曲线;将不同数量的MSCs与K562细胞共培养测定K562细胞的增殖率曲线;流式细胞仪检测K562细胞周期以及凋亡的变化。
结果
与单独K562细胞培养相比,与相同数量MSCs共培养后,K562细胞生长受抑;与不同数量MSCs共培养后,其对K562细胞的抗增殖作用呈剂量依赖性;细胞周期分析发现K562细胞与MSCs共培养后,G0/G1期以及G2/M期的细胞增加, S期的细胞减少。共培养24 h、48 h、72 h后用流式细胞仪检测其凋亡率,发现K562细胞的凋亡率下降。
结论
正常人骨髓间充质干细胞能导致K562细胞生长抑制,阻止K562细胞周期的运行,凋亡率下降,且在一定范围内,随着间充质干细胞数量的增加其对K562细胞的抗增殖作用增强。
目的
观察骨髓间充质干细胞(BMMSC)对小鼠急性淋巴细胞白血病(ALL)模型中白血病细胞的作用;
方法
将携带绿色荧光蛋白(eGFP)基因标记的P388细胞(小鼠急性淋巴细胞白血病细胞系)腹腔接种于DBA/2小鼠建立ALL小鼠动物模型,静脉输注体外培养的骨髓间充质干细胞。记录小鼠存活时间;监测小鼠血常规;流式细胞仪检测组织器官标本中的eGFP+细胞的百分比;观察各小鼠脏器发生的病理学变化以及检测输注MSC的小鼠体内Y染色体的存在。
结果
骨髓间充质干细胞能延长ALL小鼠的生存时间,但其血常规变化不大; MSCs能够减少各组织白血病细胞的浸润,并具有向各组织定植的能力。
结论
骨髓间充质干细胞能影响小鼠急性淋巴细胞白血病(ALL)模型中白血病细胞的生长。
Objective To compare K562 cell proliferation, cell cycle and apoptosis before and after adhesive culture with MSCs of the same and the different counts.,so as to study the effect of human bone marrow mesenchymal stem cells (MSCs) on the growth of K562 cells.
Methods Culture system of bone marrow MSCs and co-culture system of K562 cells and BMSCs in vitro were established. And K562 cell proliferation curves were drawn. K562 cells were co-cultured with different counts of BMSCs and their growth curves were shown. Cell cycle and apoptosis were determined by flow cytometry.
Results The proliferation of K562 cells cultured with the same amounts of MSCs was inhibited. When co-cultured with the different amounts of MSCs cells, MSCs exhibited a dose-dependent anti-proliferation effect on K562 cells. The percentages of G0/G1 and G2/M phase of K562 cells co-cultured with MSCs were higher than those of the control while the percentage of S phase cells was lower.
Conclusions The normal bone marrow mesenchymal stem cells can inhibit the proliferation, progress of cell cycle and the rate of apoptosis of K562 cells. As the number of mesenchymal stem cells increased, their anti-proliferation effect on the K562 cells was enhanced in a certain range.
Objective To observe the effect of bone marrow mesenchymal stem cell(sBMMSCs)on leukemic cells of acute lymphocytic leukemia model.
Methods The model of acute lymphocytic leukemia was established by using P388 cell line expressing enhanced green flourescent protein (eGFP) to inoculate in the abdominal cavities of DBA/2 mice.And then the models were intravenously infused BMMSCs which were cultured in vitro.The control groups were injected with P388 cell line or sodium chloride alone. The percentages of eGFP+ cells of samples were evaluated by flow cytometry, the survial time was recorded,blood routine of mice was monitored, the pathological changes of organs was observed and the exist of Y chromosomal was detected.
Results BMMSCs could decrease the infiltration of leukemic cells in the tissues of ALL mice, increase the survival time of mice and have the ability of orientation planting. But blood routine was not changed obviously.
Conclusions BMMSCs can affect the growth of leukemic cells in acute lymphocytic leukemia model.
引文
1 Barry, F.P., Murphy, J.M. Mesenchymal stem cells: clinical applications and biological characterization.Int J Biochem Cell Biol.2004, 36(4):568-584.
2 Antonio Uccelli, Lorenzo Moretta, Vito Pistoia.Immunoregulatory function of mesenchymal stem cells. Eur. J. Immunol. 2006, 36(10):2566-2573.
3 Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D and Dazzi F.Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia.2007, 21(2):304-310.
4林玉梅,卜丽梅,杨少娟,高申,张桂珍.人骨髓间充质干细胞对K562细胞增殖和化疗敏感性的影响中国实验血液学杂志.2006, 14(2): 308-312.
5 Halla BM, Fortney JE, Taylor L, Wood H, Wang L, Adams S, Davis S, Gibson LF. Stromal cells expressing elevated VCAM-1 enhance survival of B lineage tumor cells. Cancer Lett, 2004, 207(2):229-239.
6 Zhu W, Xu W, Jiang R.Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol, 2006, 80(3):267-274.
7 Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J and Jorgensen C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102(10): 3837-3844.
8 Wu XZ, Chen D. Bone marrow-derived cells: roles in solid tumor. Neoplasma. 2007, 54(1):1-6.
1 Lazennec G, Jorgensen C. Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem Cells 2008;26:1387-1394.
2史剑慧,许小平,程文英,李林,牛玉宏,葛均波.小鼠微小残留白血病模型的建立,复旦学报(医学版).2002,29 (5),383-386.
3蔡文琴,王伯.实用免疫细胞化学与核酸分子杂交技术.成都:四川科学技术出版社.1994,204-230.
4许小平,费新红,陈莉,吕书晴,高磊,倪雄,许晓巍,贾新颜.表达绿荧光蛋白的多药耐药微小残留白血病细胞的小鼠模型.中国实验血液学杂志.2005:13(6):1014-1017.
5 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(4):663-667
6 Ohlsson LB, Varas L, Kjellman C, Edvardsen K, Lindvall M. Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix. Exp Mol Pathol, 2003, 75(3): 248-255.
7 Nakamura K, Ito Y, Kawano Y, Kurozumi K ,Kobune M ,Tsuda H ,Bizen A ,Honmou O ,Niitsu Y ,Hamada H .Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Therapy, 2004,11(14):1155-1164.
8 Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J,Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF.. Human bone marrow derived mesenchymal stem cells in the treatment of gliomas. Cancer Res,2005,65(8):3307 3318.
9 ]Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M.. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res, 2002,62 (13):3603-3608.
10 Menon LG, Picinich S, Koneru R, Gao H, Lin SY, Koneru M, Mayer-Kuckuk P, Glod J, Banerjee D.Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells 2007; 25:520–528
11 Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu JB,Cao WK, Han CX , Chen YC . Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol, 2006, 80(3):267-274.
12 Djouad F, Bony C, Apparailly F, Louis-Plence P, Jorgensen C, No?l D. Earlier onset of syngeneic tumors in the presence of mesenchymal stem cells.Transplantation, 2006, 82(8):1060-1066.
13 Komarova S, Kawakami Y, Stoff-Khalili MA , Curiel DT , Pereboeva L. Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses.Mol Cancer Ther, 2006, 5(3):755-766.
14 Kucerova L, Altanerova V, Matuskova M,Tyciakova S and Altaner C. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy.Cancer Res, 2007, 67(13):6304-6313.
15 Karnoub AE, Dash AB, Vo AP , Sullivan A, Brooks MW,George W,Bell GW,Richardson AL,Polyak K,Ross Tubo R and Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 2007, 449:557-563.
1 Barry, F.P., Murphy, J.M. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol. 2004, 36(4):568-584.
2 Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors growth in allogeneic animals. Blood, 2003, 102(10):3837-3844.
3 Halla BM, Fortney JE, Taylor L, et al. Stromal cells expressing elevatedVCAM-1 enhance survival of B lineage tumor cells. Cancer Lett, 2004, 207(2):229-239.
4 Zhu W, Xu W, Jiang R, Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol, 2006, 80(3):267-274.
5 Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D and Dazzi F.Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia. 2007, 21(2):304-310.
6 Aguilar S, Nye E, Chan J,et al. Murine but not Human Mesenchymal Stem Cells Generate Osteosarcoma-Like Lesions in the Lung. Stem Cells. 2007; 0: 2006-0762v1.
7 Mueller MM,Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer, 2004, 4(11):839-849.
8 Wu XZ, Chen D. Bone marrow-derived cells: roles in solid tumor. Neoplasma. 2007, 54(1):1-6.
9 Ganss R. Tumor stroma fosters neovascularization by recruitment of progenitor cells into the tumor bed. J Cell Mol Med. 2006, 10(4):857-865.
10 Fuller J. Stem cell aging and cancer. Sci Aging Knowledge Environ. 2006,2006(9):pe12.
11 Pelicci PG. Do tumor-suppressive mechanisms contribute to organism aging by inducing stem cell senescence? J Clin Invest. 2004, 113(1):4-7.
12江逊,崔鹏程,陈文弦,等.人骨髓间充质干细胞体外培养及生物特性的观察,第四军医大学学报,2003,24(4):352-353
13 Tolar J, Nauta AJ, Osborn MJ,et al. Sarcoma Derived from Cultured Mesenchymal Stem Cells. Stem Cells. 2007, 25(2):371-379.
14 Zhou YF, Bosch-Marce M, Okuyama H, et al. Spontaneous transformation of cultured mouse bone marrow-derived stromal cells. Cancer Res. 2006, 66(22):10849-10854.
15 Miura M, Miura Y, Padilla-Nash HM,et al.Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation. Stem Cells. 2006, 24(4):1095-1103.
16 Serakinci N,Guldberg P,Burns JS,et al.Adult human mesenchymal stem cell as a target for neoplastic transformation.Oncogene,2004,23 (29):5095-5098.
17 Khakoo AY, Pati S, Anderson SA, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006, 203(5):1235-1247.
18 Nakamura K, Ito Y, Kawano Y,et al. Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model.Gene Therapy, 2004, 11:1155-1164.
19 Ohlsson LB, Varas L, Kjellman C, et al. Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix. Exp Mol Pathol, 2003, 75: 248-255.
20 LI Chun-Hui,JIAO Bao-Hua, Effect of Bone Marrow Stromal Cells Transfected with Interleukin 18 on Growth of Intracranial Glioma in Rats.Chinese Journal of Cancer, 2007, 26(4):38-43
21 Elzaouk L, Moelling K, Pavlovic J. Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model,Exp Dermatol. 2006, 15(11): 865-874.
22 Sohara Y ,Shimada H ,Minkin C ,et al. Bone marrow mesenchymal stem cells provide an alternate pathway of osteoclast activation and bone destruction by cancer cells..Cancer Res, 2005, 65(4):1129-1135.
2 Antonio Uccelli, Lorenzo Moretta, Vito Pistoia.Immunoregulatory function of mesenchymal stem cells. Eur. J. Immunol. 2006, 36(10):2566-2573.
3 Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D and Dazzi F.Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia.2007, 21(2):304-310.
4林玉梅,卜丽梅,杨少娟,高申,张桂珍.人骨髓间充质干细胞对K562细胞增殖和化疗敏感性的影响中国实验血液学杂志.2006, 14(2): 308-312.
5 Halla BM, Fortney JE, Taylor L, Wood H, Wang L, Adams S, Davis S, Gibson LF. Stromal cells expressing elevated VCAM-1 enhance survival of B lineage tumor cells. Cancer Lett, 2004, 207(2):229-239.
6 Zhu W, Xu W, Jiang R.Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol, 2006, 80(3):267-274.
7 Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J and Jorgensen C. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102(10): 3837-3844.
8 Wu XZ, Chen D. Bone marrow-derived cells: roles in solid tumor. Neoplasma. 2007, 54(1):1-6.
1 Lazennec G, Jorgensen C. Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem Cells 2008;26:1387-1394.
2史剑慧,许小平,程文英,李林,牛玉宏,葛均波.小鼠微小残留白血病模型的建立,复旦学报(医学版).2002,29 (5),383-386.
3蔡文琴,王伯.实用免疫细胞化学与核酸分子杂交技术.成都:四川科学技术出版社.1994,204-230.
4许小平,费新红,陈莉,吕书晴,高磊,倪雄,许晓巍,贾新颜.表达绿荧光蛋白的多药耐药微小残留白血病细胞的小鼠模型.中国实验血液学杂志.2005:13(6):1014-1017.
5 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(4):663-667
6 Ohlsson LB, Varas L, Kjellman C, Edvardsen K, Lindvall M. Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix. Exp Mol Pathol, 2003, 75(3): 248-255.
7 Nakamura K, Ito Y, Kawano Y, Kurozumi K ,Kobune M ,Tsuda H ,Bizen A ,Honmou O ,Niitsu Y ,Hamada H .Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Therapy, 2004,11(14):1155-1164.
8 Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J,Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF.. Human bone marrow derived mesenchymal stem cells in the treatment of gliomas. Cancer Res,2005,65(8):3307 3318.
9 ]Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M.. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res, 2002,62 (13):3603-3608.
10 Menon LG, Picinich S, Koneru R, Gao H, Lin SY, Koneru M, Mayer-Kuckuk P, Glod J, Banerjee D.Differential gene expression associated with migration of mesenchymal stem cells to conditioned medium from tumor cells or bone marrow cells. Stem Cells 2007; 25:520–528
11 Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu JB,Cao WK, Han CX , Chen YC . Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol, 2006, 80(3):267-274.
12 Djouad F, Bony C, Apparailly F, Louis-Plence P, Jorgensen C, No?l D. Earlier onset of syngeneic tumors in the presence of mesenchymal stem cells.Transplantation, 2006, 82(8):1060-1066.
13 Komarova S, Kawakami Y, Stoff-Khalili MA , Curiel DT , Pereboeva L. Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses.Mol Cancer Ther, 2006, 5(3):755-766.
14 Kucerova L, Altanerova V, Matuskova M,Tyciakova S and Altaner C. Adipose tissue-derived human mesenchymal stem cells mediated prodrug cancer gene therapy.Cancer Res, 2007, 67(13):6304-6313.
15 Karnoub AE, Dash AB, Vo AP , Sullivan A, Brooks MW,George W,Bell GW,Richardson AL,Polyak K,Ross Tubo R and Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 2007, 449:557-563.
1 Barry, F.P., Murphy, J.M. Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol. 2004, 36(4):568-584.
2 Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors growth in allogeneic animals. Blood, 2003, 102(10):3837-3844.
3 Halla BM, Fortney JE, Taylor L, et al. Stromal cells expressing elevatedVCAM-1 enhance survival of B lineage tumor cells. Cancer Lett, 2004, 207(2):229-239.
4 Zhu W, Xu W, Jiang R, Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol, 2006, 80(3):267-274.
5 Ramasamy R, Lam EW, Soeiro I, Tisato V, Bonnet D and Dazzi F.Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia. 2007, 21(2):304-310.
6 Aguilar S, Nye E, Chan J,et al. Murine but not Human Mesenchymal Stem Cells Generate Osteosarcoma-Like Lesions in the Lung. Stem Cells. 2007; 0: 2006-0762v1.
7 Mueller MM,Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer, 2004, 4(11):839-849.
8 Wu XZ, Chen D. Bone marrow-derived cells: roles in solid tumor. Neoplasma. 2007, 54(1):1-6.
9 Ganss R. Tumor stroma fosters neovascularization by recruitment of progenitor cells into the tumor bed. J Cell Mol Med. 2006, 10(4):857-865.
10 Fuller J. Stem cell aging and cancer. Sci Aging Knowledge Environ. 2006,2006(9):pe12.
11 Pelicci PG. Do tumor-suppressive mechanisms contribute to organism aging by inducing stem cell senescence? J Clin Invest. 2004, 113(1):4-7.
12江逊,崔鹏程,陈文弦,等.人骨髓间充质干细胞体外培养及生物特性的观察,第四军医大学学报,2003,24(4):352-353
13 Tolar J, Nauta AJ, Osborn MJ,et al. Sarcoma Derived from Cultured Mesenchymal Stem Cells. Stem Cells. 2007, 25(2):371-379.
14 Zhou YF, Bosch-Marce M, Okuyama H, et al. Spontaneous transformation of cultured mouse bone marrow-derived stromal cells. Cancer Res. 2006, 66(22):10849-10854.
15 Miura M, Miura Y, Padilla-Nash HM,et al.Accumulated Chromosomal Instability in Murine Bone Marrow Mesenchymal Stem Cells Leads to Malignant Transformation. Stem Cells. 2006, 24(4):1095-1103.
16 Serakinci N,Guldberg P,Burns JS,et al.Adult human mesenchymal stem cell as a target for neoplastic transformation.Oncogene,2004,23 (29):5095-5098.
17 Khakoo AY, Pati S, Anderson SA, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med. 2006, 203(5):1235-1247.
18 Nakamura K, Ito Y, Kawano Y,et al. Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model.Gene Therapy, 2004, 11:1155-1164.
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