Genetically-modified stem cells in treatment of human diseases: Tissue kallikrein (KLK1)-based targeted therapy (Review)

International Journal of Molecular Medicine

Volumn 41, Issue 3, 2018, Pages 1177-1186

  Devetzi, Marina ^a   Goulielmaki, Maria ^a   Khoury, Nicolas ^a   Spandidos, Demetrios A ^b   Sotiropoulou, Georgia ^c   Christodoulou, Ioannis ^a   Zoumpourlis, Vassilis ^a  

^a INSTITUTE OF BIOLOGY   (Greece)

^b UNIVERSITY OF CRETE   (Greece)

^c UNIVERSITY OF PATRAS   (Greece)

Author keywords

Genetic modification; Kallikrein kinin system; Stem cells; Targeted therapy; Tissue kallikrein (KLK1)

Indexed keywords

ADENOVIRUS VECTOR; KALLIKREIN; KLK1 PROTEIN; UNCLASSIFIED DRUG; TISSUE KALLIKREIN;

BRAIN ISCHEMIA; CARDIOVASCULAR DISEASE; CELL MIGRATION; CELL POPULATION; CELL TRANSFORMATION; CEREBROVASCULAR DISEASE; CLINICAL OUTCOME; DISEASES; DNA MODIFICATION; ENDOTHELIAL PROGENITOR CELL; ENGRAFTMENT; EXPERIMENTAL ANIMAL; GENE TARGETING; HEART DISEASE; HEART MUSCLE ISCHEMIA; HEART PROTECTION; HOMEOSTASIS; HUMAN; IMMUNOMODULATION; KIDNEY DISEASE; KIDNEY ISCHEMIA; KLK1 GENE; MESENCHYMAL STEM CELL; MOLECULARLY TARGETED THERAPY; MULTIPOTENT STEM CELL; NEUROLOGIC DISEASE; NONHUMAN; PARACRINE SIGNALING; PHENOTYPE; PLEIOTROPY; PRIORITY JOURNAL; PROTEIN FUNCTION; RENAL PROTECTION; REVIEW; STEM CELL TRANSPLANTATION; TISSUE INJURY; VASCULAR DISEASE; VIRAL GENE DELIVERY SYSTEM; GENETIC ENGINEERING; METABOLISM; STEM CELL;

DISEASE; GENETIC ENGINEERING; HUMANS; MOLECULAR TARGETED THERAPY; STEM CELL TRANSPLANTATION; STEM CELLS; TISSUE KALLIKREINS;

EID: 85041010184     PISSN: 11073756     EISSN: 1791244X     Source Type: Journal    
DOI: 10.3892/ijmm.2018.3361     Document Type: Review

References (144)

1. Moreau ME, Garbacki N, Molinaro G, Brown NJ, Marceau F and Adam A: The kallikrein-kinin system: Current and future pharmacological targets. J Pharmacol Sci 99: 6-38, 2005.
2. Kashuba E, Bailey J, Allsup D and Cawkwell L: The kininkallikrein system: Physiological roles, pathophysiology and its relationship to cancer biomarkers. Biomarkers 18: 279-296, 2013.
3. Bourdet B, Pécher C, Minville V, Jaafar A, Allard J, Blaes N, Girolami JP and Tack I: Distribution and expression of B2-kinin receptor on human leukocyte subsets in young adults and elderly using flow cytometry. Neuropeptides 44: 155-161, 2010.
4. Chao J, Bledsoe G, Yin H and Chao L: The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction. Biol Chem 387: 665-675, 2006.
5. Emami N and Diamandis EP: New insights into the functional mechanisms and clinical applications of the kallikrein-related peptidase family. Mol Oncol 1: 269-287, 2007.
6. Bryant JW and Shariat-Madar Z: Human plasma kallikrein-kinin system: Physiological and biochemical parameters. Cardiovasc Hematol Agents Med Chem 7: 234-250, 2009.
7. Hillmeister P and Persson PB: The kallikrein-kinin system. Acta Physiol (Oxf) 206: 215-219, 2012.
8. Björkqvist J, Jämsä A and Renné T: Plasma kallikrein: The bradykinin-producing enzyme. Thromb Haemost 110: 399-407, 2013.
9. Borgoño CA and Diamandis EP: The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer 4: 876-890, 2004.
10. Sotiropoulou G, Pampalakis G and Diamandis EP: Functional roles of human kallikrein-related peptidases. J Biol Chem 284: 32989-32994, 2009.
11. Lee KD: Applications of mesenchymal stem cells: An updated review. Chang Gung Med J 31: 228-236, 2008.
12. Christodoulou I, Kolisis FN, Papaevangeliou D and Zoumpourlis V: Comparative evaluation of human mesenchymal stem cells of fetal (Wharton's jelly) and adult (adipose tissue) origin during prolonged in vitro expansion: Considerations for cytotherapy. Stem Cells Int 2013: 246134, 2013.
13. Shafei AE, Ali MA, Ghanem HG, Shehata AI, Abdelgawad AA, Handal HR, Talaat KA, Ashaal AE and El-Shal AS: Mesenchymal stem cells therapy: A promising cell based therapy for treatment of myocardial infraction. J Gene Med 19: e2995, 2017.
14. Rhee KJ, Lee JI and Eom YW: Mesenchymal stem cell-mediated effects of tumor support or suppression. Int J Mol Sci 16: 30015-30033, 2015.
15. Dominici M, Le Blanc K, Mueller I, Slaper-C ortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ and Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8: 315-317, 2006.
16. Rehman J, Li J, Orschell CM and March KL: Peripheral blood 'endothelial progenitor cells' are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 107: 1164-1169, 2003.
17. Hristov M and Weber C: Endothelial progenitor cells: Characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med 8: 498-508, 2004.
18. Kränkel N, Luscher TF and Landmesser U: 'Endothelial progenitor cells' as a therapeutic strategy in cardiovascular disease. Curr Vasc Pharmacol 10: 107-124, 2012.
19. Fu SS, Li FJ, Wang YY, You AB, Qie YL, Meng X, Li JR, Li BC, Zhang Y and Da Li Q: Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression. PLoS One 8: e73035, 2013.
20. Kamei N, Atesok K and Ochi M: The use of endothelial progenitor cells for the regeneration of musculoskeletal and neural tissues. Stem Cells Int 2017: 1960804, 2017.
21. Hickson LJ, Eirin A and Lerman LO : Challenges and opportunities for stem cell therapy in patients with chronic kidney disease. Kidney Int 89: 767-778, 2016.
22. Liao S, Luo C, Cao B, Hu H, Wang S, Yue H, Chen L and Zhou Z: Endothelial progenitor cells for ischemic stroke: Update on basic research and application. Stem Cells Int 2017: 2193432, 2017.
23. Sage EK, Thakrar RM and Janes SM: Genetically modified mesenchymal stromal cells in cancer therapy. Cytotherapy 18: 1435-1445, 2016.
24. Uccelli A, Moretta L and Pistoia V: Mesenchymal stem cells in health and disease. Nat Rev Immunol 8: 726-736, 2008.
25. Mishra PJ, Mishra PJ, Glod JW and Banerjee D: Mesenchymal stem cells: Flip side of the coin. Cancer Res 69: 1255-1258, 2009.
26. Ye Z, Wang Y, Xie HY and Zheng SS: Immunosuppressive effects of rat mesenchymal stem cells: Involvement of CD 4+CD 25+ regulatory T cells. Hepatobiliary Pancreat Dis Int 7: 608-614, 2008.
27. Borlongan CV : Bone marrow stem cell mobilization in stroke: A 'bonehead' may be good after all! Leukemia 25: 1674-1686, 2011.
28. Kortesidis A, Zannettino A, Isenmann S, Shi S, Lapidot T and Gronthos S: Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells. Blood 105: 3793-3801, 2005.
29. Fong CY, Richards M, Manasi N, Biswas A and Bongso A: Comparative growth behaviour and characterization of stem cells from human Wharton's jelly. Reprod Biomed Online 15: 708-718, 2007.
30. Fong CY, Chak LL, Biswas A, Tan JH, Gauthaman K, Chan WK and Bongso A: Human Wharton's jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev 7: 1-16, 2011.
31. Weiss ML, Anderson C, Medicetty S, Seshareddy KB, Weiss RJ, VanderWerff I, Troyer D and McIntosh KR: Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells 26: 2865-2874, 2008.
32. Prasanna SJ and Jahnavi VS: Wharton's jelly mesenchymal stem cells as off-the-shelf cellular therapeutics: A closer look into their regenerative and immunomodulatory properties. Open Tissue Eng Regen Med J 4: 28-38, 2011.
33. Yoon J, Min BG, Kim Y- H, Shim WJ, Ro YM and Lim D- S: Differentiation, engraftment and functional effects of pre-treated mesenchymal stem cells in a rat myocardial infarct model. Acta Cardiol 60: 277-284, 2005.
34. Tang J, Xie Q, Pan G, Wang J and Wang M: Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg 30: 353-361, 2006.
35. Wolf D, Reinhard A, Krause U, Seckinger A, Katus HA, Kuecherer H and Hansen A: Stem cell therapy improves myocardial perfusion and cardiac synchronicity: New application for echocardiography. J Am Soc Echocardiogr 20: 512-520, 2007.
36. Yang J, Zhou W, Zheng W, Ma Y, Lin L, Tang T, Liu J, Yu J, Zhou X and Hu J: Effects of myocardial transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor for the improvement of heart function and angiogenesis after myocardial infarction. Cardiology 107: 17-29, 2007.
37. Guo J, Lin GS, Bao CY, Hu ZM and Hu MY: Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction. Inflammation 30: 97-104, 2007.
38. Xu X, Xu Z, Xu Y and Cui G: Effects of mesenchymal stem cell transplantation on extracellular matrix after myocardial infarction in rats. Coron Artery Dis 16: 245-255, 2005.
39. Gao L, Bledsoe G, Yin H, Shen B, Chao L and Chao J: Tissue kallikrein-modified mesenchymal stem cells provide enhanced protection against ischemic cardiac injury after myocardial infarction. Circ J 77: 2134-2144, 2013.
40. Amado LC, Saliaris AP, Schuleri KH, St John M, Xie JS, Cattaneo S, Durand DJ, Fitton T, Kuang JQ, Stewart G, et al: Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci USA 102: 11474-11479, 2005.
41. Goradel NH, Hoor FG, Negahdari B, Malekshahi ZV, Hashemzehi M, Masoudifar A and Mirzaei H: Stem cell therapy: A new therapeutic option for cardiovascular diseases. J Cell Biochem 119: 95-104, 2018.
42. Chen XL, Zhang Q, Zhao R and Medford RM : Superoxide, H2O2, and iron are required for TNF-alpha-induced MCP-1 gene expression in endothelial cells: Role of Rac1 and NAD PH oxidase. Am J Physiol Heart Circ Physiol 286: H1001-H1007, 2004.
43. Caplan AI and Dennis JE : Mesenchymal stem cells as trophic mediators. J Cell Biochem 98: 1076-1084, 2006.
44. Choi SH, Jung SY, Kwon SM and Baek SH: Perspectives on stem cell therapy for cardiac regeneration. Advances and challenges. Circ J 76: 1307-1312, 2012.
45. Zhang W, Liu XC, Yang L, Zhu DL, Zhang YD, Chen Y and Zhang HY: Wharton's jelly-derived mesenchymal stem cells promote myocardial regeneration and cardiac repair after miniswine acute myocardial infarction. Coron Artery Dis 24: 549-558, 2013.
46. Deng J, Petersen BE, Steindler DA, Jorgensen ML and Laywell ED : Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24: 1054-1064, 2006.
47. Tropel P, Platet N, Platel JC, Noël D, Albrieux M, Benabid AL and Berger F: Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells. Stem Cells 24: 2868-2876, 2006.
48. Tseng PY, Chen CJ, Sheu CC, Yu CW and Huang YS: Spontaneous differentiation of adult rat marrow stromal cells in a long-term culture. J Vet Med Sci 69: 95-102, 2007.
49. Dezawa M, Hoshino M and Ide C: Treatment of neurodegenerative diseases using adult bone marrow stromal cell-derived neurons. Expert Opin Biol Ther 5: 427-435, 2005.
50. Kim EJ, Kim N and Cho SG: The potential use of mesenchymal stem cells in hematopoietic stem cell transplantation. Exp Mol Med 45: e2, 2013.
51. Aleynik A, Gernavage KM, Mourad YS, Sherman LS, Liu K, Gubenko YA and Rameshwar P: Stem cell delivery of therapies for brain disorders. Clin Transl Med 3: 24, 2014.
52. Nikolic WV, Hou H, Town T, Zhu Y, Giunta B, Sanberg CD, Zeng J, Luo D, Ehrhart J, Mori T, et al: Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular β-amyloid deposits in Alzheimer mice. Stem Cells Dev 17: 423-439, 2008.
53. Tanna T and Sachan V: Mesenchymal stem cells: Potential in treatment of neurodegenerative diseases. Curr Stem Cell Res Ther 9: 513-521, 2014.
54. Galieva LR, Mukhamedshina YO, Arkhipova SS and Rizvanov AA : Human umbilical cord blood cell transplantation in neuroregenerative strategies. Front Pharmacol 8: 628, 2017.
55. Lee NK, Na DL and Chang JW: Killing two birds with one stone: The multifunctional roles of mesenchymal stem cells in the treatment of neurodegenerative and muscle diseases. Histol Histopathol: Nov 30, 2017 (Epub ahead of print).
56. Gärtner A, Pereira T, Gomes R, Luís AL, França ML, Geuna S, Armada-da-Silva P and Maurício AC: Mesenchymal stem cells from extra-embryonic tissues for tissue engineering -.regeneration of the peripheral nerve. In: Advances in Biomaterials Science and Biomedical Applications. Pignatello R (ed). InTech, 2013.
57. Ribeiro J, Gartner A, Pereira T, Gomes R, Lopes MA, Gonçalves C, Varejão A, Luís AL and Maurício AC: Perspectives of employing mesenchymal stem cells from the Wharton's jelly of the umbilical cord for peripheral nerve repair. Int Rev Neurobiol 108: 79-120, 2013.
58. Chambers BE and Wingert RA : Renal progenitors: Roles in kidney disease and regeneration. World J Stem Cells 8: 367-375, 2016.
59. Peired AJ, Sisti A and Romagnani P: Mesenchymal stem cell-based therapy for kidney disease: A review of clinical evidence. Stem Cells Int 2016: 4798639, 2016.
60. Aghajani Nargesi A, Lerman LO and Eirin A: Mesenchymal stem cell-derived extracellular vesicles for kidney repair: Current status and looming challenges. Stem Cell Res Ther 8: 273, 2017.
61. Tögel F, Hu Z, Weiss K, Isaac J, Lange C and Westenfelder C: Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol 289: F31-F 42, 2005.
62. Lange C, Tögel F, Ittrich H, Clayton F, Nolte-E rnsting C, Zander AR and Westenfelder C: Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int 68: 1613-1617, 2005.
63. Chao J, Bledsoe G and Chao L: Kallikrein-kinin in stem cell therapy. World J Stem Cells 6: 448-457, 2014.
64. Ezquer F, Ezquer M, Simon V, Pardo F, Yañez A, Carpio D and Conget P: Endovenous administration of bone-marrow-derived multipotent mesenchymal stromal cells prevents renal failure in diabetic mice. Biol Blood Marrow Transplant 15: 1354-1365, 2009.
65. Fang Y, Tian X, Bai S, Fan J, Hou W, Tong H and Li D: Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatory cytokines and the p38 MA PK signaling pathway. Int J Mol Med 30: 85-92, 2012.
66. Castiglione RC, Maron-Gutierrez T, Barbosa CM, Ornellas FM, Barreira AL, Dibarros CB, Vasconcelos-dos-Santos A, Paredes BD, Pascarelli BM, Diaz BL, et al: Bone marrow-derived mononuclear cells promote improvement in glomerular function in rats with early diabetic nephropathy. Cell Physiol Biochem 32: 699-718, 2013.
67. Zhu XY, Urbieta-C aceres V, Krier JD, Textor SC, Lerman A and Lerman LO : Mesenchymal stem cells and endothelial progenitor cells decrease renal injury in experimental swine renal artery stenosis through different mechanisms. Stem Cells 31: 117-125, 2013.
68. Eirin A, Zhu XY, Krier JD, Tang H, Jordan KL, Grande JP, Lerman A, Textor SC and Lerman LO : Adipose tissue-derived mesenchymal stem cells improve revascularization outcomes to restore renal function in swine atherosclerotic renal artery stenosis. Stem Cells 30: 1030-1041, 2012.
69. Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC, Cantino D and Camussi G: Isolation of renal progenitor cells from adult human kidney. Am J Pathol 166: 545-555, 2005.
70. Angelotti ML, Ronconi E, Ballerini L, Peired A, Mazzinghi B, Sagrinati C, Parente E, Gacci M, Carini M, Rotondi M, et al: Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 30: 1714-1725, 2012.
71. Papazova DA, Oosterhuis NR, Gremmels H, van Koppen A, Joles JA and Verhaar MC : Cell-based therapies for experimental chronic kidney disease: A systematic review and meta-analysis. Dis Model Mech 8: 281-293, 2015.
72. Ma H, Wu Y, Xu Y, Sun L and Zhang X: Human umbilical mesenchymal stem cells attenuate the progression of focal segmental glomerulosclerosis. Am J Med Sci 346: 486-493, 2013.
73. Belingheri M, Lazzari L, Parazzi V, Groppali E, Biagi E, Gaipa G, Giordano R, Rastaldi MP, Croci D, Biondi A, et al: Allogeneic mesenchymal stem cell infusion for the stabilization of focal segmental glomerulosclerosis. Biologicals 41: 439-445, 2013.
74. Sun L, Akiyama K, Zhang H, Yamaza T, Hou Y, Zhao S, Xu T, Le A and Shi S: Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells 27: 1421-1432, 2009.
75. Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, et al: Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 62: 2467-2475, 2010.
76. Munir H and McGettrick HM: Mesenchymal stem cell therapy for autoimmune disease: Risks and rewards. Stem Cells Dev 24: 2091-2100, 2015.
77. Flores AI, Gómez-Gómez GJ, Masedo-González Á and Martínez- Montiel MP: Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy? World J Stem Cells 7: 343-351, 2015.
78. Fang TC, Pang CY, Chiu SC, Ding DC and Tsai RK: Renoprotective effect of human umbilical cord-derived mesenchymal stem cells in immunodeficient mice suffering from acute kidney injury. PLoS One 7: e46504, 2012.
79. Werner N and Nickenig G: Endothelial progenitor cells in health and atherosclerotic disease. Ann Med 39: 82-90, 2007.
80. Jujo K, Ii M and Losordo DW: Endothelial progenitor cells in neovascularization of infarcted myocardium. J Mol Cell Cardiol 45: 530-544, 2008.
81. Choi JH, Kim KL, Huh W, Kim B, Byun J, Suh W, Sung J, Jeon ES, Oh HY and Kim DK: Decreased number and impaired angiogenic function of endothelial progenitor cells in patients with chronic renal failure. Arterioscler Thromb Vasc Biol 24: 1246-1252, 2004.
82. Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM and Dimmeler S: Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89: E1-E 7, 2001.
83. Schuh A, Liehn EA, Sasse A, Hristov M, Sobota R, Kelm M, Merx MW and Weber C: Transplantation of endothelial progenitor cells improves neovascularization and left ventricular function after myocardial infarction in a rat model. Basic Res Cardiol 103: 69-77, 2008.
84. Umemura T and Higashi Y: Endothelial progenitor cells: Therapeutic target for cardiovascular diseases. J Pharmacol Sci 108: 1-6, 2008.
85. Yao Y, Sheng Z, Li Y, Yan F, Fu C, Li Y, Ma G, Liu N, Chao J and Chao L: Tissue kallikrein promotes cardiac neovascularization by enhancing endothelial progenitor cell functional capacity. Hum Gene Ther 23: 859-870, 2012.
86. Simard T, Jung RG, Motazedian P, Di Santo P, Ramirez FD, Russo JJ, Labinaz A, Yousef A, Anantharam B, Pourdjabbar A and Hibbert B: Progenitor cells for arterial repair: Incremental advancements towards therapeutic reality. Stem Cells Int 2017: 8270498, 2017.
87. Kwon O, Miller S, Li N, Khan A, Kadry Z and Uemura T: Bone marrow-derived endothelial progenitor cells and endothelial cells may contribute to endothelial repair in the kidney immediately after ischemia-reperfusion. J Histochem Cytochem 58: 687-694, 2010.
88. Patschan D, Krupincza K, Patschan S, Zhang Z, Hamby C and Goligorsky MS: Dynamics of mobilization and homing of endothelial progenitor cells after acute renal ischemia: Modulation by ischemic preconditioning. Am J Physiol Renal Physiol 291: F176-F 185, 2006.
89. Rosell A, Morancho A, Navarro-Sobrino M, Martínez-Saez E, Hernandez-Guillamon M, Lope-Piedrafita S, Barceló V, Borrás F, Penalba A, García-Bonilla L and Montaner J: Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice. PLoS One 8: e73244, 2013.
90. Li YF, Ren LN, Guo G, Cannella LA, Chernaya V, Samuel S, Liu SX, Wang H and Yang XF: Endothelial progenitor cells in ischemic stroke: An exploration from hypothesis to therapy. J Hematol Oncol 8: 33, 2015.
91. Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS and Dzau VJ : Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med 9: 1195-1201, 2003.
92. Dzau VJ, Gnecchi M and Pachori AS: Enhancing stem cell therapy through genetic modification. J Am Coll Cardiol 46: 1351-1353, 2005.
93. Mastri M, Lin H and Lee T: Enhancing the efficacy of mesenchymal stem cell therapy. World J Stem Cells 6: 82-93, 2014.
94. Park JS, Suryaprakash S, Lao YH and Leong KW: Engineering mesenchymal stem cells for regenerative medicine and drug delivery. Methods 84: 3-16, 2015.
95. Moradian Tehrani R, Verdi J, Noureddini M, Salehi R, Salarinia R, Mosalaei M, Simonian M, Alani B, Ghiasi MR, Jaafari MR, et al: Mesenchymal stem cells: A new platform for targeting suicide genes in cancer. J Cell Physiol: July 13, 2017 (Epub ahead of print).
96. Tang YL, Tang Y, Zhang YC, Qian K, Shen L and Phillips MI : Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol 46: 1339-1350, 2005.
97. Matsumoto R, Omura T, Yoshiyama M, Hayashi T, Inamoto S, Koh KR, Ohta K, Izumi Y, Nakamura Y, Akioka K, et al: Vascular endothelial growth factor-expressing mesenchymal stem cell transplantation for the treatment of acute myocardial infarction. Arterioscler Thromb Vasc Biol 25: 1168-1173, 2005.
98. Gnecchi M, He H, Melo LG, Noiseaux N, Morello F, de Boer RA, Zhang L, Pratt RE, Dzau VJ and Ingwall JS: Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing Akt on cardiac metabolism after myocardial infarction. Stem Cells 27: 971-979, 2009.
99. Chen Y, Qian H, Zhu W, Zhang X, Yan Y, Ye S, Peng X, Li W and Xu W: Hepatocyte growth factor modification promotes the amelioration effects of human umbilical cord mesenchymal stem cells on rat acute kidney injury. Stem Cells Dev 20: 103-113, 2011.
100. Yuan L, Wu MJ, Sun HY, Xiong J, Zhang Y, Liu CY, Fu LL, Liu DM, Liu HQ and Mei CL : VE GF- modified human embryonic mesenchymal stem cell implantation enhances protection against cisplatin-induced acute kidney injury. Am J Physiol Renal Physiol 300: F207-F 218, 2011.
101. Regoli D, Plante GE and Gobeil F Jr: Impact of kinins in the treatment of cardiovascular diseases. Pharmacol Ther 135: 94-111, 2012.
102. Xiong W, Chen LM, Woodley-M iller C, Simson JA and Chao J: Identification, purification, and localization of tissue kallikrein in rat heart. Biochem J 267: 639-646, 1990.
103. Nolly H, Carbini LA, Scicli G, Carretero OA and Scicli AG: A local kallikrein-kinin system is present in rat hearts. Hypertension 23: 919-923, 1994.
104. Wolf WC, Harley RA, Sluce D, Chao L and Chao J: Localization and expression of tissue kallikrein and kallistatin in human blood vessels. J Histochem Cytochem 47: 221-228, 1999.
105. Agata J, Chao L and Chao J: Kallikrein gene delivery improves cardiac reserve and attenuates remodeling after myocardial infarction. Hypertension 40: 653-659, 2002.
106. Yao YY, Yin H, Shen B, Chao L and Chao J: Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction. Regul Pept 140: 12-20, 2007.
107. Yao YY, Yin H, Shen B, Smith RS Jr, Liu Y, Gao L, Chao L and Chao J: Tissue kallikrein promotes neovascularization and improves cardiac function by the Akt-glycogen synthase kinase-3beta pathway. Cardiovasc Res 80: 354-364, 2008.
108. Yin H, Chao L and Chao J: Kallikrein/kinin protects against myocardial apoptosis after ischemia/reperfusion via Akt-glycogen synthase kinase-3 and Akt-Bad.14-3-3 signaling pathways. J Biol Chem 280: 8022-8030, 2005.
109. Westermann D, Schultheiss HP and Tschöpe C: New perspective on the tissue kallikrein-kinin system in myocardial infarction: Role of angiogenesis and cardiac regeneration. Int Immunopharmacol 8: 148-154, 2008.
110. Yin H, Chao L and Chao J: Nitric oxide mediates cardiac protection of tissue kallikrein by reducing inflammation and ventricular remodeling after myocardial ischemia/reperfusion. Life Sci 82: 156-165, 2008.
111. Yayama K, Wang C, Chao L and Chao J: Kallikrein gene delivery attenuates hypertension and cardiac hypertrophy and enhances renal function in Goldblatt hypertensive rats. Hypertension 31: 1104-1110, 1998.
112. Wolf WC, Yoshida H, Agata J, Chao L and Chao J: Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and cardiac remodeling in chronic renal failure. Kidney Int 58: 730-739, 2000.
113. Bledsoe G, Chao L and Chao J: Kallikrein gene delivery attenuates cardiac remodeling and promotes neovascularization in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 285: H1479-H1488, 2003.
114. Chao J, Shen B, Gao L, Xia CF, Bledsoe G and Chao L: Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing. Biol Chem 391: 345-355, 2010.
115. Spillmann F, Graiani G, Van Linthout S, Meloni M, Campesi I, Lagrasta C, Westermann D, Tschöpe C, Quaini F, Emanueli C and Madeddu P: Regional and global protective effects of tissue kallikrein gene delivery to the peri-infarct myocardium. Regen Med 1: 235-254, 2006.
116. Emanueli C, Minasi A, Zacheo A, Chao J, Chao L, Salis MB, Straino S, Tozzi MG, Smith R, Gaspa L, et al: Local delivery of human tissue kallikrein gene accelerates spontaneous angiogenesis in mouse model of hindlimb ischemia. Circulation 103: 125-132, 2001.
117. Emanueli C and Madeddu P: Angiogenesis therapy with human tissue kallikrein for the treatment of ischemic diseases. Arch Mal Coeur Vaiss 97: 679-687, 2004.
118. Murakami H, Miao RQ, Chao L and Chao J: Adenovirusmediated kallikrein gene transfer inhibits neointima formation via increased production of nitric oxide in rat artery. Immunopharmacology 44: 137-143, 1999.
119. Murakami H, Yayama K, Miao RQ, Wang C, Chao L and Chao J : Kallikrein gene delivery inhibits vascular smooth muscle cell growth and neointima formation in the rat artery after balloon angioplasty. Hypertension 34: 164-170, 1999.
120. Hagiwara M, Shen B, Chao L and Chao J: Kallikrein-modified mesenchymal stem cell implantation provides enhanced protection against acute ischemic kidney injury by inhibiting apoptosis and inflammation. Hum Gene Ther 19: 807-819, 2008.
121. González A, Ravassa S, Beaumont J, López B and Díez J: New targets to treat the structural remodeling of the myocardium. J Am Coll Cardiol 58: 1833-1843, 2011.
122. Tschöpe C, Walther T, Kön J, Spillmann F, Westermann D, Escher F, Pauschinger M, Pesquero JB, Bader M, Schultheiss HP and Noutsias M: Prevention of cardiac fibrosis and left ventricular dysfunction in diabetic cardiomyopathy in rats by transgenic expression of the human tissue kallikrein gene. FA SEB J 18: 828-835, 2004.
123. Yao Y, Sheng Z, Li Y, Fu C, Ma G, Liu N, Chao J and Chao L: Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of akt and increased angiogenesis. Lab Invest 93: 577-591, 2013.
124. Naicker S, Naidoo S, Ramsaroop R, Moodley D and Bhoola K: Tissue kallikrein and kinins in renal disease. Immunopharmacology 44: 183-192, 1999.
125. Katori M and Majima M: A missing link between a high salt intake and blood pressure increase. J Pharmacol Sci 100: 370-390, 2006.
126. Sharma JN and Narayanan P: The kallikrein-kinin pathways in hypertension and diabetes. Prog Drug Res 69: 15-36, 2014.
127. Uehara Y, Hirawa N, Kawabata Y, Suzuki T, Ohshima N, Oka K, Ikeda T, Goto A, Toyo-oka T and Kizuki K: Long-term infusion of kallikrein attenuates renal injury in Dahl salt-sensitive rats. Hypertension 24: 770-778, 1994.
128. Chao J, Zhang JJ, Lin KF and Chao L: Adenovirus-mediated kallikrein gene delivery reverses salt-induced renal injury in Dahl salt-sensitive rats. Kidney Int 54: 1250-1260, 1998.
129. Hirawa N, Uehara Y, Suzuki T, Kawabata Y, Numabe A, Gomi T, lkeda T, Kizuki K and Omata M: Regression of glomerular injury by kallikrein infusion in Dahl salt-sensitive rats is a bradykinin B2-receptor-mediated event. Nephron 81: 183-193, 1999.
130. Bledsoe G, Shen B, Yao Y, Zhang JJ, Chao L and Chao J: Reversal of renal fibrosis, inflammation, and glomerular hypertrophy by kallikrein gene delivery. Hum Gene Ther 17: 545-555, 2006.
131. Zhang JJ, Bledsoe G, Kato K, Chao L and Chao J: Tissue kallikrein attenuates salt-induced renal fibrosis by inhibition of oxidative stress. Kidney Int 66: 722-732, 2004.
132. Liu Y, Bledsoe G, Hagiwara M, Yang ZR, Shen B, Chao L and Chao J: Blockade of endogenous tissue kallikrein aggravates renal injury by enhancing oxidative stress and inhibiting matrix degradation. Am J Physiol Renal Physiol 298: F1033-F 1040, 2010.
133. Xia CF, Bledsoe G, Chao L and Chao J: Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA- salt hypertensive rats. Am J Physiol Renal Physiol 289: F622-F 631, 2005.
134. Schanstra JP, Neau E, Drogoz P, Arevalo Gomez MA, Lopez Novoa JM, Calise D, Pecher C, Bader M, Girolami JP and Bascands JL : In vivo bradykinin B2 receptor activation reduces renal fibrosis. J Clin Invest 110: 371-379, 2002.
135. Bledsoe G, Shen B, Yao YY, Hagiwara M, Mizell B, Teuton M, Grass D, Chao L and Chao J: Role of tissue kallikrein in prevention and recovery of gentamicin-induced renal injury. Toxicol Sci 102: 433-443, 2008.
136. Dellalibera-J oviliano R, Reis ML and Donadi EA : Kinin system in lupus nephritis. Int Immunopharmacol 1: 1889-1896, 2001.
137. Liu K, Li QZ, Delgado-V ega AM, Abelson AK, Sánchez E, Kelly JA, Li L, Liu Y, Zhou J, Yan M, et al; Profile Study Group; Italian Collaborative Group; German Collaborative Group; Spanish Collaborative Group; Argentinian Collaborative Group; SLE GEN Consortium: Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans. J Clin Invest 119: 911-923, 2009.
138. Li Y, Raman I, Du Y, Yan M, Min S, Yang J, Fang X, Li W, Lu J, Zhou XJ, et al: Kallikrein transduced mesenchymal stem cells protect against anti-GBM disease and lupus nephritis by ameliorating inflammation and oxidative stress. PLoS One 8: e67790, 2013.
139. Xia CF, Yin H, Borlongan CV, Chao L and Chao J: Kallikrein gene transfer protects against ischemic stroke by promoting glial cell migration and inhibiting apoptosis. Hypertension 43: 452-459, 2004.
140. Zhang JJ, Chao L, Chao J, Chu Y and Heistad DD : Adenovirus-mediated kallikrein gene delivery reduces aortic thickening and stroke-induced death rate in Dahl salt-sensitive rats. Stroke 30: 1925-1931, discussion 1931-1932, 1999.
141. Xia CF, Yin H, Yao YY, Borlongan CV, Chao L and Chao J: Kallikrein protects against ischemic stroke by inhibiting apoptosis and inflammation and promoting angiogenesis and neurogenesis. Hum Gene Ther 17: 206-219, 2006.
142. Chao J and Chao L: Experimental therapy with tissue kallikrein against cerebral ischemia. Front Biosci 11: 1323-1327, 2006.
143. Kizuki K, Iwadate H and Ookubo R: Growth-stimulating effect of kallikrein on rat neural stem cells - II. Immunocytochemical analysis and specificity of the enzyme for neural stem cells. Yakugaku Zasshi 127: 919-922, 2007.
144. Liu L, Liu H, Yang F, Chen G, Zhou H, Tang M, Zhang R and Dong Q: Tissue kallikrein protects cortical neurons against hypoxia/reoxygenation injury via the ER K1/2 pathway. Biochem Biophys Res Commun 407: 283-287, 2011.