The challenge of pancreatic cancer therapy and novel treatment strategy using engineered mesenchymal stem cells

Cancer Gene Therapy

Volumn 21, Issue 1, 2014, Pages 12-23

  Moniri, M R ^a   Dai, L J ^a,b   Warnock, G L ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b HUBEI UNIVERSITY OF MEDICINE   (China)

Author keywords

mesenchymal stem cells; pancreatic cancer

Indexed keywords

ANIMALS; EPITHELIAL-MESENCHYMAL TRANSITION; GENETIC THERAPY; HUMANS; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STROMAL CELLS; NEOVASCULARIZATION, PATHOLOGIC; PANCREATIC NEOPLASMS; SIGNAL TRANSDUCTION; WNT SIGNALING PATHWAY;

EID: 84893799599     PISSN: 09291903     EISSN: 14765500     Source Type: Journal    
DOI: 10.1038/cgt.2013.83     Document Type: Review

References (196)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62: 10-29.
2. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E et al. Cancer statistics 2004. CA Cancer J Clin 2004; 54: 8-29.
3. Iovanna J, Mallmann MC, Goncalves A, Turrini O, Dagorn JC. Current knowledge on pancreatic cancer. Front Oncol 2012; 2: 6.
4. Canadian Cancer Society's Steering Committee on Cancer Statistics. Canadian Cancer Statistics 2012. Canadian Cancer Society: Toronto, ON, Canada, 2012, ISSN 0835-2976.
5. Smeenk HG, de Castro SM, Jeekel JJ, Kazemier G, Busch OR, Incrocci L et al. Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil: a first step to neoadjuvant treatment? Dig Surg 2005; 22: 191-197.
6. Michaud DS. Epidemiology of pancreatic cancer. Minerva Chir 2004; 59: 99-111.
7. Githens S. Differentiation and development of the pancreas in animals. In: Go VLW (ed), The Pancreas: Biology, Pathobiology and Disease. 2nd edn. Raven Press, 1993, pp 21-55.
8. Bardeesy N, Sharpless NE, DePinho RA, Merlino G. The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model. Sem Cancer Biol 2001; 11: 201-218.
9. Elayat AA, el-Naggar MM, Tahir M. An immunocytochemical and morphometric study of the rat pancreatic islets. J Anat 1995; 186(Pt 3): 629-637.
10. Li J, Wientjes MG, Au JL. Pancreatic cancer: pathobiology, treatment options, and drug delivery. AAPS J 2010; 12: 223-232.
11. Warshaw AL, Gu ZY, Wittenberg J, Waltman AC. Preoperative staging and assessment of resectability of pancreatic cancer. Arch Surg 1990; 125: 230-233.
12. Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 1996; 223: 273-279.
13. Yeo CJ, Cameron JL, Lillemoe KD, Sohn TA, Campbell KA, Sauter PK et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 2002; 236: 355-366, discussion 366-8.
14. Christians KK, Tsai S, Tolat PP, Evans DB. Critical steps for pancreaticoduodenectomy in the setting of pancreatic adenocarcinoma. J Surg Oncol 2012; 107: 33-38.
15. Macmillan Cancer Support. Chemotherapy for pancreatic cancer. 2012. http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Pancreas/ Treatingpancreaticcancer/Treatmentoverview.aspx.
16. Mahalingam D, Kelly KR, Swords RT, Carew J, Nawrocki ST, Giles FJ. Emerging drugs in the treatment of pancreatic cancer. Expert Opin Emerg Drugs 2009; 14: 311-328.
17. Barton-Burke M. Gemcitabine: a pharmacologic and clinical overview. Cancer Nurs 1999; 22: 176-183.
18. Eastman A. The mechanism of action of cisplatin: from adducts to apoptosis. In: Cisplatin. Verlag Helvetica Chimica Acta, Fachbereich Chemie: Dortmund, Germany, 2006, pp 111-134.
19. Bhattacharyya M, Lemoine NR. Gene therapy developments for pancreatic cancer. Best Pract Res Clin Gastroenterol 2006; 20: 285-298.
20. Breitbach CJ, Burke J, Jonker D, Stephenson J, Haas AR, Chow LQ et al. Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature 2011; 477: 99-102.
21. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. New Engl J Med 2011; 365: 725-733.
22. Monahan PE, Samulski RJ. Adeno-associated virus vectors for gene therapy: more pros than cons? Mol Med Today 2000; 6: 433-440.
23. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
24. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674.
25. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988; 53: 549-554.
26. Smit VTHBM, Boot AJM, Smits AMM, Fleuren GJ, Cornelisse CJ, Bos JL. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 1988; 16: 7773-7782.
27. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 1988; 53: 549-554.
28. Kranenburg O. The KRAS oncogene: past, present, and future. Biochim Biophys Acta 2005; 1756: 81-82.
29. Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res 2000; 6: 2969-2972.
30. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK et al. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci USA 1996; 93: 3636-3641.
31. Miwa W, Yasuda J, Murakami Y, Yashima K, Sugano K, Sekine T et al. Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer. Biochem Biophys Res Commun 1996; 225: 968-974.
32. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev 1999; 13: 2905-2927.
33. Downward J. PI 3-kinase, Akt and cell survival. Semin Cell Dev Biol 2004; 15: 177-182.
34. Liang J, Slingerland JM. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle 2003; 2: 339-345.
35. Downward J. Ras signalling and apoptosis. Curr Opin Genet Dev 1998; 8: 49-54.
36. Bondar VM, Sweeney-Gotsch B, Andreeff M, Mills GB, McConkey DJ. Inhibition of the phosphatidylinositol 30-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. Mol Cancer Ther 2002; 1: 989-997.
37. Okami K, Wu L, Riggins G, Cairns P, Goggins M, Evron E et al. Analysis of PTEN/MMAC1 alterations in aerodigestive tract tumors. Cancer Res 1998; 58: 509-511.
38. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 1992; 90: 1352-1360.
39. Ebert M, Yokoyama M, Friess H, Kobrin MS, Buchler MW, Korc M. Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer. Int J Cancer 1995; 62: 529-535.
40. Yamanaka Y, Friess H, Kobrin MS, Buchler M, Kunz J, Beger HG et al. Overexpression of HER2/neu oncogene in human pancreatic carcinoma. Hum Pathol 1993; 24: 1127-1134.
41. Bergmann U, Funatomi H, Yokoyama M, Beger HG, Korc M. Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res 1995; 55: 2007-2011.
42. Kornmann M, Ishiwata T, Beger HG, Korc M. Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer: evidence for autocrine and paracrine actions. Oncogene 1997; 15: 1417-1424.
43. Harding MW. Immunophilins, mTOR, and pharmacodynamic strategies for a targeted cancer therapy. Clin Cancer Res 2003; 9: 2882-2886.
44. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18: 1926-1945.
45. Morgensztern D, McLeod HL. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 2005; 16: 797-803.
46. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell 2006; 127: 469-480.
47. Heiser PW, Lau J, Taketo MM, Herrera PL, Hebrok M. Stabilization of beta-catenin impacts pancreas growth. Development 2006; 133: 2023-2032.
48. Murtaugh LC, Law AC, Dor Y, Melton DA. Beta-catenin is essential for pancreatic acinar but not islet development. Development 2005; 132: 4663-4674.
49. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009; 17: 9-26.
50. Morris JPT, Wang SC, Hebrok MKRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma. Nat Rev Cancer 2010; 10: 683-695.
51. Malbon CC. Frizzleds: new members of the superfamily of G-protein-coupled receptors. Front Biosci 2004; 9: 1048-1058.
52. Zeng G, Germinaro M, Micsenyi A, Monga NK, Bell A, Sood A et al. Aberrant Wnt/beta-catenin signaling in pancreatic adenocarcinoma. Neoplasia 2006; 8: 279-289.
53. Schwartz AL, Malgor R, Dickerson E, Weeraratna AT, Slominski A, Wortsman J et al. Phenylmethimazole decreases Toll-like receptor 3 and noncanonical Wnt5a expression in pancreatic cancer and melanoma together with tumor cell growth and migration. Clin Cancer Res 2009; 15: 4114-4122.
54. Pilarsky C, Ammerpohl O, Sipos B, Dahl E, Hartmann A, Wellmann A et al. Activation of Wnt signalling in stroma from pancreatic cancer identified by gene expression profiling. J Cell Mol Med 2008; 12: 2823-2835.
55. Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 1996; 271: 12687-12690.
56. Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995; 3: 673-682.
57. Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer 2008; 8: 782-798.
58. Wu GS. TRAIL as a target in anti-cancer therapy. Cancer Lett 2009; 285: 1-5.
59. Zhang L, Fang B. Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 2005; 12: 228-237.
60. Wiley SR SK, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 1995; 3: 673-682.
61. Kayagaki N, Yamaguchi N, Nakayama M, Eto H, Okumura K, Yagita H. Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: A novel mechanism for the antitumor effects of type I IFNs. J Exp Med 1999; 189: 1451-1460.
62. Fanger NA, Maliszewski CR, Schooley K, Griffith TS. Human dendritic cells mediate cellular apoptosis via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). J Exp Med 1999; 190: 1155-1164.
63. Griffith TS, Wiley SR, Kubin MZ, Sedger LM, Maliszewski CR, Fanger NA. Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL. J Exp Med 1999; 189: 1343-1354.
64. Kemp TJ, Moore JM, Griffith TS. Human B cells express functional TRAIL/Apo-2 ligand after CpG-containing oligodeoxynucleotide stimulation. J Immunol 2004; 173: 892-899.
65. Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, Perussia B. Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med 1998; 188: 2375-2380.
66. Holoch PA, Griffith TS. TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies. Eur J Pharmacol 2009; 625: 63-72.
67. Zhu DM, Shi J, Liu S, Liu Y, Zheng D. HIV infection enhances TRAIL-induced cell death in macrophage by down-regulating decoy receptor expression and generation of reactive oxygen species. PloS ONE 2011; 6: e18291.
68. Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2002; 2: 420-430.
69. Ashkenazi A, Dixit VM. Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 1999; 11: 255-260.
70. Falschlehner C, Emmerich CH, Gerlach B, Walczak H. TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol 2007; 39: 1462-1475.
71. Liu W, Zhou Y, Reske SN, Shen C. PTEN mutation: many birds with one stone in tumorigenesis. Anticancer Res 2008; 28: 3613-3619.
72. Yuan XJ, Whang YE. PTEN sensitizes prostate cancer cells to death receptormediated and drug-induced apoptosis through a FADD-dependent pathway. Oncogene 2002; 21: 319-327.
73. Forster MD, Dedes KJ, Sandhu S, Frentzas S, Kristeleit R, Ashworth A et al. Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial cancer. Nat Rev. Clin Oncol 2011; 8: 302-306.
74. Carnero A. The PKB/AKT pathway in cancer. Curr Pharm Des 2010; 16: 34-44.
75. Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol 2009; 4: 127-150.
76. Sakurada A, Suzuki A, Sato M, Yamakawa H, Orikasa K, Uyeno S et al. Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary. Jpn J Cancer Res 1997; 88: 1025-1028.
77. Asano T, Yao Y, Zhu J, Li D, Abbruzzese JL, Reddy SA. The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells. Oncogene 2004; 23: 8571-8580.
78. Altomare DA, Tanno S, De Rienzo A, Klein-Szanto AJ, Skele KL, Hoffman JP et al. Frequent activation of AKT2 kinase in human pancreatic carcinomas. J Cell Biochem 2002; 87: 470-476.
79. Ebert MP, Fei G, Schandl L, Mawrin C, Dietzmann K, Herrera P et al. Reduced PTEN expression in the pancreas overexpressing transforming growth factorbeta 1. Br J Cancer 2002; 86: 257-262.
80. Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL et al. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci USA 2009; 106: 3806-3811.
81. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102: 3837-3844.
82. Vasudevan KM, Burikhanov R, Goswami A, Rangnekar VM. Suppression of PTEN expression is essential for antiapoptosis and cellular transformation by oncogenic Ras. Cancer Res 2007; 67: 10343-10350.
83. Chow JY, Quach KT, Cabrera BL, Cabral JA, Beck SE, Carethers JM. RAS/ERK modulates TGFbeta-regulated PTEN expression in human pancreatic adenocarcinoma cells. Carcinogenesis 2007; 28: 2321-2327.
84. Chow JY, Dong H, Quach KT, Van Nguyen PN, Chen K, Carethers JM. TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKCalpha activation in pancreatic cancer cells. Am J Physiol Gastrointest Liver Physiol 2008; 294: G899-G905.
85. Ma J, Sawai H, Ochi N, Matsuo Y, Xu D, Yasuda A et al. PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells. Mol Cell Biochem 2009; 331: 161-171.
86. Hill R, Calvopina JH, Kim C, Wang Y, Dawson DW, Donahue TR et al. PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res 2010; 70: 7114-7124.
87. Pappas G, Zumstein LA, Munshi A, Hobbs M, Meyn RE. Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity. Cancer Gene Ther 2007; 14: 543-549.
88. Jin H, Xu CX, Kim HW, Chung YS, Shin JY, Chang SH et al. Urocanic acid-modified chitosan-mediated PTEN delivery via aerosol suppressed lung tumorigenesis in K-ras(LA1) mice. Cancer Gene Ther 2008; 15: 275-283.
89. Adachi T, Hanaka S, Masuda T, Yoshihara H, Nagase H, Ohta K. Transduction of phosphatase and tensin homolog deleted on chromosome 10 into eosinophils attenuates survival, chemotaxis, and airway inflammation. J Immunol 2007; 179: 8105-8111.
90. Friedenstein AJ, Piatetzky II S, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 1966; 16: 381-390.
91. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP. Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 1968; 6: 230-247.
92. Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9: 641-650.
93. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
94. Fiorina P, Jurewicz M, Augello A, Vergani A, Dada S, La Rosa S et al. Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes. J Immunol 2009; 183: 993-1004.
95. Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood 2007; 110: 3499-3506.
96. Le Blanc K, Pittenger M. Mesenchymal stem cells: progress toward promise. Cytotherapy 2005; 7: 36-45.
97. Loebinger MR, Janes SM. Stem cells as vectors for antitumour therapy. Thorax 2010; 65: 362-369.
98. Moniri MR, Sun XY, Rayat J, Dai D, Ao Z, He Z et al. TRAIL-engineered pancreasderived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells. Cancer Gene Ther 2012; 19: 652-658.
99. Hu Y, Liao L, Wang Q, Ma L, Ma G, Jiang X et al. Isolation and identification of mesenchymal stem cells from human fetal pancreas. J Lab Clin Med 2003; 141: 342-349.
100. Sun XY, Nong J, Qin K, Lu H, Moniri MR, Dai LJ et al. MSC(TRAIL)-mediated HepG2 cell death in direct and indirect co-cultures. Anticancer Res 2011; 31: 3705-3712.
101. Luria EA, Panasyuk AF, Friedenstein AY. Fibroblast colony formation from monolayer cultures of blood cells. Transfusion 1971; 11: 345-349.
102. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG. Circulating skeletal stem cells. J Cell Biol 2001; 153: 1133-1140.
103. Warejcka DJ, Harvey R, Taylor BJ, Young HE, Lucas PA. A population of cells isolated from rat heart capable of differentiating into several mesodermal phenotypes. J Surg Res 1996; 62: 233-242.
104. Katz AJ, Tholpady A, Tholpady SS, Shang H, Ogle RC. Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells 2005; 23: 412-423.
105. Young HE, Mancini ML, Wright RP, Smith JC, Black Jr. AC, Reagan CR et al. Mesenchymal stem cells reside within the connective tissues of many organs. Dev Dyn 1995; 202: 137-144.
106. 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.
107. Tsai MS, Lee JL, Chang YJ, Hwang SM. Isolation of human multipotent mesenchymal stem cells from second-trimester amniotic fluid using a novel twostage culture protocol. Hum Reprod 2004; 19: 1450-1456.
108. Vaananen HK. Mesenchymal stem cells. Ann Med 2005; 37: 469-479.
109. Ohyabu Y, Kaul Z, Yoshioka T, Inoue K, Sakai S, Mishima H et al. Stable and nondisruptive in vitro/in vivo labeling of mesenchymal stem cells by internalizing quantum dots. Hum Gene Ther 2009; 20: 217-224.
110. Anjos-Afonso F, Siapati EK, Bonnet D. In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions. J Cell Sci 2004; 117(Pt 23): 5655-5664.
111. da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006; 119(Pt 11): 2204-2213.
112. Short B, Brouard N, Occhiodoro-Scott T, Ramakrishnan A, Simmons PJ. Mesenchymal stem cells. Arch Med Res 2003; 34: 565-571.
113. Dai LJ, Moniri MR, Zeng ZR, Zhou JX, Rayat J, Warnock GL. Potential implications of mesenchymal stem cells in cancer therapy. Cancer Lett 2011; 305: 8-20.
114. Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol 2009; 217: 318-324.
115. Sakaguchi Y, Sekiya I, Yagishita K, Muneta T. Comparison of human stem cells derived from various mesenchymal tissues: superiority of synovium as a cell source. Arthritis Rheum 2005; 52: 2521-2529.
116. Stewart K, Monk P, Walsh S, Jefferiss CM, Letchford J, Beresford JN. STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. Cell Tissue Res 2003; 313: 281-290.
117. Pittenger MF, Martin BJ. Mesenchymal stem cells and their potential as cardiac therapeutics. Circ Res 2004; 95: 9-20.
118. Delorme B, Ringe J, Gallay N, Le Vern Y, Kerboeuf D, Jorgensen C et al. Specific plasma membrane protein phenotype of culture-amplified and native human bone marrow mesenchymal stem cells. Blood 2008; 111: 2631-2635.
119. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8: 726-736.
120. Giordano A, Galderisi U, Marino IR. From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 2007; 211: 27-35.
121. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317.
122. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418: 41-49.
123. Majumdar MK, Keane-Moore M, Buyaner D, Hardy WB, Moorman MA, McIntosh KR et al. Characterization and functionality of cell surface molecules on human mesenchymal stem cells. J Biomed Sci 2003; 10: 228-241.
124. Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R et al. Transcoronary transplantation of progenitor cells after myocardial infarction. New Engl J Med 2006; 355: 1222-1232.
125. Schachinger V, Assmus B, Erbs S, Elsasser A, Haberbosch W, Hambrecht R et al. Intracoronary infusion of bone marrow-derived mononuclear cells abrogates adverse left ventricular remodelling post-acute myocardial infarction: insights from the reinfusion of enriched progenitor cells and infarct remodelling in acute myocardial infarction (REPAIR-AMI) trial. Eur J Heart Fail 2009; 11: 973-979.
126. Qu C, Mahmood A, Lu D, Goussev A, Xiong Y, Chopp M. Treatment of traumatic brain injury in mice with marrow stromal cells. Brain Res 2008; 1208: 234-239.
127. Chopp M, Li Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol 2002; 1: 92-100.
128. Zhang ZX, Guan LX, Zhang K, Zhang Q, Dai LJ. A combined procedure to deliver autologous mesenchymal stromal cells to patients with traumatic brain injury. Cytotherapy 2008; 10: 134-139.
129. Dezawa M, Hoshino M, Ide C. Treatment of neurodegenerative diseases using adult bone marrow stromal cell-derived neurons. Expert Opin Biol Ther 2005; 5: 427-435.
130. Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F et al. Autologous hematopoietic stem cell transplantation for type 1 diabetes. Ann N Y Acad Sci 2008; 1150: 220-229.
131. Li DS, Warnock GL, Tu HJ, Ao Z, He Z, Lu H et al. Do immunotherapy and beta cell replacement play a synergistic role in the treatment of type 1 diabetes? Life Sci 2009; 85: 549-556.
132. Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res 2009; 2: 16-25.
133. Albini A, Sporn MB. The tumour microenvironment as a target for chemoprevention. Nat Rev Cancer 2007; 7: 139-147.
134. Zischek C, Niess H, Ischenko I, Conrad C, Huss R, Jauch KW et al. Targeting tumor stroma using engineered mesenchymal stem cells reduces the growth of pancreatic carcinoma. Ann Surg 2009; 250: 747-753.
135. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. New Engl J Med 1986; 315: 1650-1659.
136. Sasportas LS, Kasmieh R, Wakimoto H, Hingtgen S, van de Water JA, Mohapatra G et al. Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USAm 2009; 106: 4822-4827.
137. Sonabend AM, Ulasov IV, Tyler MA, Rivera AA, Mathis JM, Lesniak MS. Mesenchymal stem cells effectively deliver an oncolytic adenovirus to intracranial glioma. Stem Cells 2008; 26: 831-841.
138. Yang B, Wu X, Mao Y, Bao W, Gao L, Zhou P et al. Dual-targeted antitumor effects against brainstem glioma by intravenous delivery of tumor necrosis factor-related, apoptosis-inducing, ligand-engineered human mesenchymal stem cells. Neurosurgery 2009; 65: 610-624, discussion 624.
139. Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol 2010; 184: 5885-5894.
140. Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 2009; 27: 2614-2623.
141. Khakoo AY, Pati S, Anderson SA, Reid W, Elshal MF, Rovira II et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med 2006; 203: 1235-1247.
142. Loebinger MR, Kyrtatos PG, Turmaine M, Price AN, Pankhurst Q, Lythgoe MF et al. Magnetic resonance imaging of mesenchymal stem cells homing to pulmonary metastases using biocompatible magnetic nanoparticles. Cancer Res 2009; 69: 8862-8867.
143. Menon LG, Picinich S, Koneru R, Gao H, Lin SY, Koneru M et al. 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.
144. 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.
145. Dwyer RM, Potter-Beirne SM, Harrington KA, Lowery AJ, Hennessy E, Murphy JM et al. Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clin Cancer Res 2007; 13: 5020-5027.
146. Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J et al. Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 2006; 24: 1254-1264.
147. Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USAm 2004; 101: 18117-18122.
148. Schmidt NO, Przylecki W, Yang W, Ziu M, Teng Y, Kim SU et al. Brain tumor tropism of transplanted human neural stem cells is induced by vascular endothelial growth factor. Neoplasia 2005; 7: 623-629.
149. Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J et al. Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 2005; 65: 3307-3318.
150. Motaln H, Schichor C, Lah TT. Human mesenchymal stem cells and their use in cell-based therapies. Cancer 2010; 116: 2519-2530.
151. Irene Von Lü ttichau MN, Wechselberger Alexandra, Peters Christina, Henger Anna, Seliger Christian, Djafarzadeh Roghieh et al. Human Adult CD34-progenitor cells functionally express the chemokine receptors CCR1, CCR4, CCR7, CXCR5, and CCR10 but Not CXCR4. Stem Cells Dev 2005; 14: 329-336.
152. Salem HK, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 2010; 28: 585-596.
153. Kemp KC, Hows J, Donaldson C. Bone marrow-derived mesenchymal stem cells. Leuk Lymphoma 2005; 46: 1531-1544.
154. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells 2006; 24: 1030-1041.
155. De Becker A, Van Hummelen P, Bakkus M, Vande Broek I, De Wever J, De Waele M et al. Migration of culture-expanded human mesenchymal stem cells through bone marrow endothelium is regulated by matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-3. Haematologica 2007; 92: 440-449.
156. Li H, Fan X, Houghton J. Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem 2007; 101: 805-815.
157. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 2001; 166: 678-689.
158. Ghannam S, Bouffi C, Djouad F, Jorgensen C, Noel D. Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications. Stem cell Res Ther 2010; 1: 2.
159. Shi Y, Hu G, Su J, Li W, Chen Q, Shou P et al. Mesenchymal stem cells: a new strategy for immunosuppression and tissue repair. Cell Res 2010; 20: 510-518.
160. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI et al. Mesenchymal stem cellmediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2: 141-150.
161. Polchert D, Sobinsky J, Douglas G, Kidd M, Moadsiri A, Reina E et al. IFN-gamma activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur J Immunol 2008; 38: 1745-1755.
162. Noel D, Djouad F, Bouffi C, Mrugala D, Jorgensen C. Multipotent mesenchymal stromal cells and immune tolerance. Leuk Lymphoma 2007; 48: 1283-1289.
163. Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005; 105: 2821-2827.
164. Corcione A, Benvenuto F, Ferretti E, Giunti D, Cappiello V, Cazzanti F et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107: 367-372.
165. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99: 3838-3843.
166. Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004; 103: 4619-4621.
167. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105: 1815-1822.
168. Maccario R, Podesta M, Moretta A, Cometa A, Comoli P, Montagna D et al. Interaction of human mesenchymal stem cells with cells involved in alloantigenspecific immune response favors the differentiation of CD4\+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005; 90: 516-525.
169. Bergmann C, Strauss L, Zeidler R, Lang S, Whiteside TL. Expansion of human T regulatory type 1 cells in the microenvironment of cyclooxygenase 2 overexpressing head and neck squamous cell carcinoma. Cancer Res 2007; 67: 8865-8873.
170. Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4\+CD25highFoxp3\+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res 2007; 13(15 Pt 1): 4345-4354.
171. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G et al. Regulatory CD4\+CD25\+ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 2001; 61: 4766-4772.
172. Lazennec G, Jorgensen C. Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem Cells 2008; 26: 1387-1394.
173. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S et al. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 2004; 94: 678-685.
174. Al-Khaldi A, Eliopoulos N, Martineau D, Lejeune L, Lachapelle K, Galipeau J. Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo. Gene Ther 2003; 10: 621-629.
175. Valdes F, Alvarez AM, Locascio A, Vega S, Herrera B, Fernandez M et al. The epithelial mesenchymal transition confers resistance to the apoptotic effects of transforming growth factor Beta in fetal rat hepatocytes. Mol Cancer Res 2002; 1: 68-78.
176. Klymkowsky MW, Savagner P. Epithelial-mesenchymal transition: a cancer researcher's conceptual friend and foe. Am J Pathol 2009; 174: 1588-1593.
177. Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S et al. Epithelialmesenchymal transition in cancer development and its clinical significance. Cancer Sci 2010; 101: 293-299.
178. Martin FT, Dwyer RM, Kelly J, Khan S, Murphy JM, Curran C et al. Potential role of mesenchymal stem cells (MSCs) in the breast tumour microenvironment: stimulation of epithelial to mesenchymal transition (EMT). Breast Cancer Res Treat 2010; 124: 317-326.
179. Lepperdinger G, Brunauer R, Jamnig A, Laschober G, Kassem M. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol 2008; 43: 1018-1023.
180. Bernardo ME, Emons JA, Karperien M, Nauta AJ, Willemze R, Roelofs H et al. Human mesenchymal stem cells derived from bone marrow display a better
181. Wang Y, Huso DL, Harrington J, Kellner J, Jeong DK, Turney J et al. Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 2005; 7: 509-519.
182. Rubio D, Garcia S, Paz MF, De la Cueva T, Lopez-Fernandez LA, Lloyd AC et al. Molecular characterization of spontaneous mesenchymal stem cell transformation. PloS One 2008; 3: e1398.
183. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H et al. Gastric cancer originating from bone marrow-derived cells. Science 2004; 306: 1568-1571.
184. 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: 663-667.
185. 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: 248-255.
186. Kidd S, Caldwell L, Dietrich M, Samudio I, Spaeth EL, Watson K et al. Mesenchymal stromal cells alone or expressing interferon-beta suppress pancreatic tumors in vivo, an effect countered by anti-inflammatory treatment. Cytotherapy 2010.
187. Qiao L, Xu Z, Zhao T, Zhao Z, ShiM, Zhao RC et al. Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res 2008; 18: 500-507.
188. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-111.
189. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature 2005; 434: 843-850.
190. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C et al. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005; 6: 314-322.
191. Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW et al. Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 2006; 442: 823-826.
192. Chen G, Shukeir N, Potti A, Sircar K, Aprikian A, Goltzman D et al. Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer 2004; 101: 1345-1356.
193. Moon RT, Kohn AD, De Ferrari GV, Kaykas A. WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet 2004; 5: 691-701.
194. Lu YR, Yuan Y, Wang XJ, Wei LL, Chen YN, Cong C et al. The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo. Cancer Biol Ther 2008; 7: 245-251.
195. Sun B, Roh KH, Park JR, Lee SR, Park SB, Jung JW et al. Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy 2009; 113: 289-298, 1 p following 298.
196. Loebinger MR, Janes SM. Stem cells as vectors for antitumour therapy. Thorax 2010; 65: 362-369.