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Vol. 84, No. 1, 2010
Issue release date: February 2010
Urol Int 2010;84:94–99

Bone Marrow Mesenchymal Stem Cells Induce Angiogenesis and Promote Bladder Cancer Growth in a Rabbit Model

Zhang K. · Shi B. · Chen J. · Zhang D. · Zhu Y. · Zhou C. · Zhao H. · Jiang X. · Xu Z.
aDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong University, and bDepartment of Urology, Qilu Hospital, Shandong University, Jinan, PR China

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Objectives: To investigate the effect of mesenchymal stem cells (MSCs) in the process of tumor development and the possibility of MSCs differentiating into vascular endothelial cells in the tumor microenvironment. Material and Methods: Twenty male New Zealand rabbits were randomly divided into 2 groups: a test group and a control group. MSCs were isolated and cultured by bone marrow cell adherence. The bladder tumor models were built by embedding a VX2 mass in swelled bladder mucosa in all of the rabbits (n = 20). One week later, 4′,6-diamidino-2-phenylindole-labeling MSCs were transplanted into tumor tissue in the test group (n = 10). Culture medium was injected into the tumor tissue of the control group (n = 10). The maximum diameter of the tumor mass was measured by ultrasound at 2 and 4 weeks after the VX2 tumor mass was embedded. All animals were sacrificed at 4 weeks. The double labeling immunofluorescence for CD146 was performed to reveal whether engrafted cells can differentiate into vascular endothelial cells. Vascular density was compared between the 2 groups. Results: There was no significant difference in the maximum diameters of the tumor masses between the 2 groups at 2 weeks (test group 0.77 ± 0.15 cm vs. control group 0.71 ± 0.15 cm, p > 0.05). The maximum diameters appeared larger in the test group at 4 weeks (test group 3.82 ± 0.94 cm vs. control group 2.28 ± 0.54 cm, p < 0.05). Immunofluorescence studies revealed some engrafted MSCs expressing a vascular endothelial cell phenotype (CD146). Furthermore, vascular density was augmented in the test group in comparison to the control group (10.1 ± 0.70/0.2 mm2 vs. 8.24 ± 0.81/0.2 mm2, p < 0.05). Conclusions: Engrafted MSCs can differentiate into vascular endothelial cells and contribute to angiogenesis in the tumor microenvironment, which may be the major pathway of promoting tumor growth.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997;276:71–74.
  2. Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, Belmonte N, Ferrari G, Leone BE, Bertuzzi F, Zerbini G, Allavena P, Bonifacio E, Piemonti L: Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood 2005;106:419–427.
  3. Klopp AH, Spaeth EL, Dembinski JL, Woodward WA, Munshi A, Meyn RE, Cox JD, Andreeff M, Marini FC: Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Res 2007;67:11687–11695.
  4. Barry FP, Murphy JM: Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004;36:568–584.
  5. Barry FP: Biology and clinical applications of mesenchymal stem cells. Birth Defects Res C Embryo Today 2003;69:250–256.
  6. Dvorak HF: Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986;315:1650–1659.
  7. 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;62:3603–3608.
  8. Chen J, Xu ZS, Zhao HF, Dong DX: Distribution and differentiation of marrow mesenchymal cells in tumor tissue: experimental with rabbits (in Chinese). Zhonghua Yi Xue Za Zhi 2007;87:2361–2364.
  9. Chen J, Xu ZS, Dong DX, Zhao HF: The foundation of rabbit bladder VX2 cancer model. Chinese J Exp Surg 2006;23:117.
  10. Zhang N, Li J, Luo R, Jiang J, Wang JA: Bone marrow mesenchymal stem cells induce angiogenesis and attenuate the remodeling of diabetic cardiomyopathy. Exp Clin Endocrinol Diabetes 2008;116:104–111.
  11. Wurmser AE, Nakashima K, Summers RG, Toni N, D’Amour KA, Lie DC, Gage FH: Cell fusion-independent differentiation of neural stem cells to the endothelial lineage. Nature 2004;430:350–356.
  12. Mancuso P, Burlini A, Pruneri G, Goldhirsch A, Martinelli G, Bertolini F: Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. Blood 2001;97:3658–3661.
  13. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM: Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002;418:41–49.
  14. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, Couter SC, Lin J, Ober J, Vaughn WK, Branco RV, Oliverira EM, He R, Geng YJ, Willerson JT, Perin EC: Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation 2005;111:150–156.
  15. Sun B, Zhang S, Ni C, Zhang D, Liu Y, Zhang W, Zhao X, Zhao C, Shi M: Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow. Stem Cells Dev 2005;14:292–298.
  16. Salvesen HB, Akslen LA: Significance of tumour-associated macrophages, vascular endothelial growth factor and thrombospondin-1 expression for tumour angiogenesis and prognosis in endometrial carcinomas. Int J Cancer 1999;84:538–543.
  17. Kerbel R, Folkman J: Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002;2:727–739.
  18. Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer 2003;3:721–732.
  19. Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C: Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 2004;22:377–384.
  20. Rak J, Yu JL, Klement G, Kerbel RS: Oncogenes and angiogenesis: signaling three-dimensional tumor growth. J Investig Dermatol Symp Proc 2000;5:24–33.
  21. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM: Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 2001;98:2396–2402.
  22. Igura K, Zhang X, Takahashi K, Mitsuru A, Yamaguchi S, Takashi TA: Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy 2004;6:543–553.
  23. Nadri S, Soleimani M, Kiani J, Atashi A, Izadpanah R: Multipotent mesenchymal stem cells from adult human eye conjunctiva stromal cells. Differentiation 2008;76:223–231.
  24. Tsai MS, Lee JL, Chang YJ, Hwang SM: Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel two-stage culture protocol. Hum Reprod 2004;19:1450–1456.
  25. Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, Champlin RE, Andreeff M: Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 2004;96:1593–1603.
  26. 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 Ther 2004;11:1155–1164.
  27. 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;65:3307–3318.

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