Stem cell therapy for cystic fibrosis: Current status and future prospects

Expert Review of Respiratory Medicine

Volumn 2, Issue 3, 2008, Pages 365-380

  Piro, Donatella ^a   Rejman, Joanna ^b   Conese, Massimo ^a  

^a UNIVERSITY OF FOGGIA   (Italy)

^b GHENT UNIVERSITY   (Belgium)

Author keywords

Bone marrow; Cystic fibrosis; Embryonic stem cell; Gene therapy; Hematopoietic stem cell; Lung; Mesenchymal stem cell; Umbilical cord blood stem cell

Indexed keywords

ADENOVIRUS VECTOR; ATAXIN 1; CD45 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; CLARA CELL PROTEIN; CORTICOSTEROID; CXCL2 CHEMOKINE; CYTOKERATIN 5; CYTOKERATIN 8; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 8; LENTIVIRUS VECTOR; LEUKOCYTE ELASTASE; LIPOSOME; MESSENGER RNA; NANOPARTICLE; PROTEIN ZO1; SODIUM CHANNEL; STROMAL CELL DERIVED FACTOR 1; SURFACTANT PROTEIN C; TRANSMEMBRANE CONDUCTANCE REGULATOR; VIRUS VECTOR;

BONE MARROW TRANSPLANTATION; CELL BASED GENE THERAPY; CELL HOMING; CLINICAL TRIAL; CYSTIC FIBROSIS; EMBRYONIC STEM CELL; EPITHELIUM CELL; GENE EXPRESSION; GENE THERAPY; HEMATOPOIETIC STEM CELL; HUMAN; LUNG DISEASE; MESENCHYMAL STEM CELL; NONHUMAN; NONVIRAL GENE DELIVERY SYSTEM; PATHOPHYSIOLOGY; PNEUMONIA; PRENATAL DIAGNOSIS; REVIEW; STEM CELL TRANSPLANTATION; UMBILICAL CORD BLOOD; VIRAL GENE DELIVERY SYSTEM;

EID: 46949085129     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.2.3.365     Document Type: Review

References (163)

1. Sueblinvong V, Suratt BT, Weiss DJ. Novel therapies for the treatment of cystic fibrosis: new developments in gene and stem cell therapy. Clin. Chest Med. 28, 361-379 (2007).
2. Abakas MH. Cystic fibrosis transmembrane conductance regulator. Structure and function of an epithelial-chloride channel. J. Biol. Chem. 275, 3729-3732 (2000).
3. Mehta A. CFTR: more than just a chloride channel. Pediatr. Pulmonol. 39, 292-298 (2005).
4. Ratjen F, Doring G. Cystic fibrosis. Lancet 361, 681-689 (2003).
5. Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DWH. Early pulmonary inflammation in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 151, 1075-1082 (1995).
6. Muhlebach MS, Stewart PW, Leigh MW, Noah TL. Quantitation of inflammatory responses to bacteria in young cystic fibrosis and control patients. Am J Respir. Crit. Care Med. 160, 186-191 (1999).
7. Balough K, McCubbin M, Weinberger M, Smits W, Ahrens R, Fick R. The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis. Pediatr. Pulmunol. 20, 63-70 (1995).
8. Sheppard MN. The pathology of cystic fibrosis. In: Cystic Fibrosis. Hodson ME, Geddes DM (Eds). Chapman & Hall, London, UK 131-149 (1995).
9. Tomashefski JF Jr, Konstan MW, Bruce MC, Abramowsky CR. The pathologic characteristics of interstitial pneumonia cystic fibrosis. A retrospective autopsy study. Am. J Clin. Pathol. 91, 522-530 (1989).
10. Wine JJ, Joo NS. Submucosal glands and airway defense. Proc. Am. Thorac. Soc. 1, 47-53 (2004).
11. Boucher RC. Cystic fibrosis: a disease of vulnerability to airway surface dehydration. Trends Mol. Med. 13, 231-240 (2007).
12. Engelhardt JF, Zepeda M, Cohn JA, Yankaskas JR, Wilson JM. Expression of the cystic fibrosis gene in adult human lung. J. Clin. Invest. 93, 737-749 (1994).
13. Kreda S, Mall M, Mengos A et al. Characterization of wild-type and ΔF508 cystic fibrosis transmembrane regulator in human respiratory epithelia. Mol. Biol. Cell. 16, 2154-2167 (2005).
14. Fang X, Song Y, Hirsch J et al. Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L242-L249 (2006).
15. + channel modulators and effect on fluid absorption across alveolar epithelial cells. Am. J Physiol. Lung Cell. Mol. Physiol. 291, L1207-L1219 (2006).
16. Rosenecker J, Huth S, Rudolph C. Gene therapy for cystic fibrosis lung disease: current status and future perspectives. Curr. Opin. Mol. Ther. 8, 439-445 (2006).
17. Koehler DR, Hitt MM, Hu J. Challenges and strategies for cystic fibrosis lung gene therapy. Mol. Ther. 4, 84-91 (2001).
18. Cotton CU, Stutts MJ, Knowles MR, Gatzy JT, Boucher RC. Abnormal apical cell membrane in cystic fibrosis respiratory epithelium. An in vitro electrophysiologic analysis. J. Clin. Invest. 79, 80-85 (1987).
19. Joo NS, Irokawa T, Robbins RC, Wine JJ. Hyposecretion, not hyperabsorption, is the basic defect of cystic fibrosis airway glands. J. Biol. Chem. 281, 7392-7398 (2006).
20. Holder E, Gricsenbach U, Li S et al. Intravenously administered oligonucleotides can be delivered to conducting airway epithelium via the bronchial circulation. Gene Ther. 13, 1628-1638 (2006).
21. Koehler DR, Hannam V, Belcastro R et al. Targeting transgene expression for cystic fibrosis gene therapy. Mol. Ther. 4, 58-65 (2001).
22. Di A, Brown ME, Deriy LV et al. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat. Cell Biol. 8, 933-944 (2006).
23. Painter RG, Valentine VG, Lanson NA Jr et al. CFTR expression in human neutrophils and the phagolysosomal. chlorination defect in cystic fibrosis. Biochemistry 45, 10260-10269 (2006).
24. Conese M, Copreni E, Di Gioia S, De Rinaldis P, Fumarulo R. Neutrophil recruitment and airway epithelial cell involvement in chronic cystic fibrosis lung disease. J. Cystic Fibrosis 2, 129-135 (2003).
25. Zeidin PL. Cystic fibrosis gene therapy trials and tribulations. Mol. Ther. 1, 5-6 (2000).
26. Davies JC, Geddes DM, Alton EWFW. Gene therapy for cystic fibrosis. J. Gene Med. 3, 409-417 (2001).
27. Lee TW, Matthews DA, Blair GE. Novel molecular approaches to cystic fibrosis gene therapy. Biochem J. 387, 1-15 (2005).
28. Griesenbach U, Geddes DM, Alton EW. Advances in cystic fibrosis gene therapy. Curr. Opin. Pulm. Med. 10, 542-546 (2004).
29. Griesenbach U, Geddes DM, Alton EW. Gene therapy for cystic fibrosis: an example for lung gene therapy. Gene Ther. 11 (Suppl. 1), S43-S50 (2004).
30. Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4, 346-358 (2003).
31. Ferrari S, Geddes DM, Alton E. Immunological hurdles to lung gene therapy. Clin. Exp. Immunol. 132, 1-8 (2003).
32. Alton EWFW, Stern M, Farley R et al. Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis: a double-blind placebo-controlled trial. Lancet 353, 947-954 (1999).
33. Yew NS, Zhao H, Wu I-H et al. Reduced inflammatory response to plasmid DNA vectors by elimination and inhibition of immunostimulatory CpG motifs. Mol. Ther. 1, 255-262 (2000).
34. Moss RB, Rodman D, Spencer LT et al. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: a multicenter, double-blind, placebo-controlled trial. Chest 125, 509-521 (2004).
35. Konstan MW, Davis PB, Wagener JS et al. Compacted DNA nanoparticles administered to the nasal mucosa of cystic fibrosis subjects are safe and demonstrate partial to complete cystic fibrosis transmembrane regulator reconstitution. Hum. Gene Ther. 15, 1255-1269 (2004).
36. Griesenbach U, Geddes DM, Alton EW. Gene therapy progress and prospects: cystic fibrosis. Gene Ther. 13, 1061-1067 (2006).
37. Wilson JM. Adeno-associated virus and lentivirus pseudotyped for lung-directed gene therapy. Proc. Am. Thorac. Soc. 1, 309-314 (2004).
38. Copreni E, Penzo M, Carrabino S, Conese M. Lentiviral-mediated gene transfer to the respiratory epithelium: a promising approach to gene therapy of cystic fibrosis. Gene Ther. 11, S67-S75 (2004).
39. Lim FY, Kobinger GP, Weiner DJ, Radu A, Wilson JM, Crombleholme TM. Human fetal trachea-SCID mouse xenografts: efficacy of vesicular stomatitis virus-G pseudotyped lentiviral-mediated gene transfer. J. Pediatr. Surg. 38, 834-839 (2003).
40. Sinn PL, Burnight ER, Hickey MA, Blissard GW, McCray PB Jr. Persistent gene expression in mouse nasal epithelia following feline immunodeficiency virus-based vector gene transfer. J. Virol. 79, 12818-12827 (2005).
41. Limberis M, Anson DS, Fuller M, Parsons DW. Recovery of airway cystic fibrosis transmembrane conductance regulator function in mice with cystic fibrosis after single-dose lentivirus-mediated gene transfer. Hum. Gene Ther. 13, 1961-1970 (2002).
42. Pilewski JM. Gene therapy for airway diseases: continued progress toward identifying and overcoming barriers to efficiency. Am. J. Respir. Cell Mol Biol. 27, 117-121 (2002).
43. Pickles RJ. Physical and biological barriers to viral vector-mediated delivery of genes to the airway epithelium. Proc. Am. Thorac. Soc. 1, 302-308 (2004).
44. Conese M, Copreni E, Piro D, Rejman J. Gene and cell therapy for the treatment of cystic fibrosis. Adv. Gene Mol. Cell. Ther. 1, 99-119 (2007).
45. Rosenocker J, Naundorf S, Gersting SW et al. Interaction of bronchoalveolar lavage fluid with polyplexes and lipoplexes: analysing the role of proteins and glycoproteins. J. Gene Med. 5, 49-60 (2003).
46. Stern M, Caplen NJ, Browning JE et al. The effect of mucolytic agents on gene transfer across a CF sputum barrier in vitro. Gene Ther. 5, 91-98 (1998).
47. Walters RW, Grunst T, Bergelson JM, Finberg RW, Welsh MJ, Zabner J. Basolateral localization of fiber receptor limits adenovirus infection from the apical surface of airway epithelia. J. Biol. Chem. 274, 10219-10226 (1999).
48. Duan D, Yue Y, Yan Z, McCray PB, Engelhardt JF. Polarity influences the efficiency of recombinant adenoassociate virus infection in differentiated airway epithelia. Hum. Gene Ther. 9, 2761-2776 (1998).
49. Anson DS, Smith GJ, Parsons DW. Gene therapy for cystic fibrosis airway disease - is clinical success imminent? Curr. Gene Ther. 6, 161-179 (2006).
50. Xenariou. S, Griesenbach U, Ferrari S et al. Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo. Gene Ther. 13, 1545-1552 (2006).
51. Otto WR. Lung epithelial stem cells. J. Pathol. 197, 527-535 (2002).
52. Liu Y, Driskell RR, Engelhardt JF. Stem cells in the lung. Methods Enzymol. 419, 285-321 (2006).
53. Rawlins EL, Hogan BL. Epithelial stem cells of the lung: privileged few or opportunities for many? Development 133, 2455-2465 (2006).
54. Giangreco A, Groot KR, Janes SM. Lung cancer and lung stem cells: strange bedfellows? Am. J. Respir. Crit. Care Med. 175, 547-553 (2007).
55. Hajj R, Baranek T, Le Naour R, Lesimple P, Puchelle E, Coraux C. Basal cells of the human adult airway surface epithelium retain transit-amplifying cell properties. Stein Cells 25, 139-148 (2007).
56. Hong KU, Reynolds SD, Watkins S, Fuchs E, Stripp BR. Basal cells are a multipotent progenitor capable of renewing the bronchial epithelium. Am. J. Pathol. 164, 577-588 (2004).
57. Borthwick DW, Shahbazian M, Krantz QT, Dorin JR, Randell SH. Evidence for stem-cell niches in the tracheal epithelium. Am. J. Respir. Cell. Mol. Biol. 24, 662-670 (2001).
58. Hong KU, Reynolds SD, Giangreco A, Hurley CM, Stripp BR. Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion. Am. J. Respir. Cell Mol. Biol. 24, 671-681 (2001).
59. Giangreco A, Reynolds SD, Stripp BR. Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction. Am. J. Pathol. 161, 173-182 (2002).
60. Reynolds SD, Giangreco A, Hong KU, McGrath KE, Ortiz LA, Stripp BR. Airway injury in lung disease pathophysiology: selective depletion of airway stem and progenitor cell pools potentiates lung inflammation and alveolar dysfunction. Am. J. Physiol, Lung Cell Mol. Pbysiol. 287, L1256-L1265 (2004).
61. Reddy R, Buckley S, Doerken M et al. Isolation of a putative progenitor subpopulation of alveolar epithelial type 2 cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 286, L658-L667 (2004).
62. Kim CF, Jackson EL, Woolfenden AE et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell 121, 823-835 (2005).
63. Ho MM, Ng AV, Lam S, Hung JY. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 67, 4827-4833 (2007).
64. Seo DC, Sung JM, Cho HJ et al. Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells. Mol. Cancer 6, 75 (2007).
65. Summer R, Kotton DN, Sun X, Ma B, Fitzsimmons & Fine A. Side population cells and Bcrp1 expression in lung. Am J Physiol. Lung Cell. Mol. Physiol. 285, L97-L104 (2003).
66. Summer R, Fitzsimmons K, Dwyer D, Murphy J, Fine A. Isolation of an adult mouse lung mesenchymal progenitor cell population. Am. J. Respir. Cell. Mol. Biol. 37, 152-159 (2007).
67. Giangreco A, Shen H, Reynolds SD, Stripp BR. Molecular phenotype of airway side population cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 286, L624-L630 (2004).
68. Summer R, Kotton DN, Liang S, Fitzsimmons K, Sun X, Fine A. Embryonic lung side population cells are hematopoietic and vascular precursors. Am. J. Respir. Cell Mol. Biol. 33, 32-40 (2005).
69. Sabatini F, Petecchia L, Tavian M, Jodon de Villeroche V, Rossi GA, Brouty-Boye D. Human bronchial fibroblasts exhibit a mesenchymal stem cell phenotype and multilineage differentiating potentialities. Lab. Invest. 85, 962-971 (2005).
70. Lama VN, Smith L, Badri L et al. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin. Invest. 117, 989-996 (2007).
71. Hennrick KT, Keeton AG, Nanua S et al. Lung cells from neonates show a mesenchymal stem cell phenotype. Am. J. Respir. Crit. Care Med. 175, 1158-1164 (2007).
72. Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8, 315-317 (2006).
73. Piro D, Lepore S, Maffione AB, Conese M. Bone marrow-derived stem cells: homing and rescue of injury in the lung. In: Hematopoietic Stem Cell Transplantation Research Advances. Neumann KB (Ed.). Nova Science Publishers, Inc., NY, USA (2008).
74. Wagers AJ, Weissman IL. Plasticity of adult stem cells. Cell 116, 639-645 (2004).
75. Barry FP, Murphy JM. Mesenchymal stem cells; clinical applications and biological characterization. Int. J. Biochem. Cell. Biol. 36, 568-584 (2004).
76. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71-74 (1997).
77. Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147 (1999).
78. Asahara T, Murohara T, Sullivan A et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964-967 (1997).
79. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol. Med. 1, 71-81 (1994).
80. Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: diffierentiation pathway and migration to wound sites. J. Immunol. 166, 7556-7562 (2001).
81. Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287, 1442-1446 (2000).
82. Herzog EL, Chai L, Krause DS. Plasticity of marrow derived stem cells. Blood 102, 3483-3493 (2003).
83. Rosenthal N. Prometheus's vulture and the stem-cell promise. N. Engl. J. Med. 349, 267-274 (2003).
84. Wang X, Willenbring H, Akkari Y et al. Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422, 897-901 (2003).
85. Vassilopoulos G, Wang PR, Russell DW. Transplanted bone marrow regenerates liver by cell fusion. Nature 422, 901-904 (2003).
86. Harris RG, Herzog EL, Bruscia EM, Grove JE, Van Arnam JS, Krause DS. Lack of fusion requirement for development of bone marrow-derived epithelia. Science 305, 90-93 (2004).
87. Herzog EL, Van Arnam J, Hu B et al. Lung-specific nuclear reprogramming is accompanied by heterokaryon formation and Y chromosome loss following bone marrow transplantation and secondary inflammation. FASEB J. 21(10), 2592-2601 (2007).
88. Krause DS, Theise ND, Collector MI et al. Multi-organ, multi-fineage engraftment by a single bone marrow-derived stem cell. Cell 105, 369-377 (2001).
89. Abe S, Boyer C, Liu X et al. Cells derived from the circulation contribute to the repair of lung injury. Am. J. Respir. Crit. Care Med. 170, 1158-1163 (2004).
90. Theise ND, Henegariu O, Grove J et al. Radiation pneumonitis in mice: a severe injury model for pneumocyte engraftment from bone marrow. Exp. Hematol. 30, 1333-1338 (2002).
91. Grove JE, Lutzko C, Priller J et al. Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium. Am. J. Respir. Cell Mol. Biol. 27, 645-651 (2002).
92. Kotton DN, Fabian AJ, Mulligan RC. Failure of bone marrow to reconstitute lung epithelium. Am J. Respir. Cell Mol. Biol. 33, 328-334 (2005).
93. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL. Little evidence for developmental plasticity of adult hematopoietic stem cells. Science 297, 2256-2259 (2002).
94. Chang JC, Summer R, Sun X, Fitzsimmons K, Fine A. Evidence that bone marrow cells do not contribute to the alveolar epithelium. Am. J. Respir Cell. Mol. Biol. 33, 335-342 (2005).
95. Herzog EL, Van Arnam J, Hu B, Krause DS. Threshold of lung injury required for the appearance of marrow-derived lung epithelia. Stem Cells 24, 1986-1992 (2006).
96. Loi R, Beckett T Goncz KK, Suratt BT, Weiss DJ. Limited restoration of cystic fibrosis lung epithelium in vivo with adult marrow derived cells. Am. J. Respir Crit. Care Med. 173, 171-179 (2006).
97. Serikov VB, Popov B, Mikhailov VM, Gupta N, Mathay MA. Evidence of temporary airway epithelial repopulation and rare clonal formation by BM-derived cells following naphthalene injury in mice. Anat. Rec. (Hoboken) 290, 1033-1045 (2007).
98. Mattsson J, Jansson M, Wernerson A, Hassan M. Lung epithelial cells and type II pneumocytes of donor origin after allogeneic hematopoietic stem cell transplantation. Transplantation 78, 154-157 (2004).
99. Zander DS, Baz MA, Cogle CR, Visner GA, Theise ND, Crawford JM. Bone marrow-derived stem-cell repopulation contributes minimally to the type II pneumocyte pool in transplanted human lungs. Transplantation 80, 206-212 (2005).
100. Zander DS, Cogle CR, Theise ND, Crawford JM. Donor-derived type II pneumocytes are rare in the lungs of allogeneic hematopoietic cell transplant recipients. Ann. Clin. Lab. Sci. 36, 47-52 (2006).
101. Neuringer IP, Randell SH. Lung stem cell update: promise and controversy. Monaldi Arch. Cbest Dis. 65, 47-51 (2006).
102. Aliotta JM, Keaney P, Passero M et al. Bone marrow production of lung cells: the impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype. Exp. Hematol. 34, 230-241 (2006).
103. 2 does not enhance development of airway epithelium from bone marrow. Mol. Ther. 12, 680-686 (2004).
104. Ortiz LA, Gambelli F, McBride C et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc. Natl Acad Sci. USA 100, 8407-8411 (2003).
105. Rojas M, Xu J, Woods CR et al Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am. J. Respir. Cell Mol. Biol. 33, 145-152 (2005).
106. Macpherson H, Keir P, Webb S et al. Bone marrow-derived SP cells can contribute to the respiratory tract of mice in vivo. J. Cell. Sci. 118, 2441-2450 (2005).
107. MacPherson H, Keir PA, Edwards CJ, Webb S, Dorin JR. Following damage, the majority of bone marrow-derived airway cells express an epithelial marker. Respir Res. 7, 145 (2006).
108. Gomperts BN, Belperio JA, Rao PN et al. Circulating progenitor epithelial cells traffic via CXCR4/CXCL12 in response to airway injury. J. Immunol. 176, 1916-1927 (2006).
109. De Rose V. Mechanisms and markets of airway inflammation in cystic fibrosis. Eur. Respir. J. 19, 333-340 (2002).
110. Wilson JW, Robertson CF. Angiogenesis in paediatric airway disease. Paediatr. Respir. Rev. 3, 219-229 (2002).
111. Li A, Dubey S, Varney MI, Dave BJ, Singh RK IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J. Immunol. 170, 3369-3376 (2003).
112. Hajj R, Lesimple P, Nawrocki-Raby B, Birembaut P, Puchelle E, Coraux C. Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis. J. Pathol. 211, 340-350 (2007).
113. Hays SR, Fahy JV. Characterizing mucous cell remodeling in cystic fibrosis: relationship to neutrophils. Am. J. Respir. Crit. Care Med. 174, 1018-1024 (2006).
114. Hilliard TN, Regamey N, Shute JK et al. Airway remodelling in children with cystic fibrosis. Thorax 62, 1074-1080 (2007).
115. Grubb BR, Boucher RC. Pathophysiology of gene-targeted mouse models for cystic fibrosis. Physiol. Rev. 79, S193-S214 (1999).
116. Zahm J-M, Gaillard D, Dupuit F et al. Early alterations in airway mucociliary clearance and inflammation of the lamina propria in CF mice. Am. J. Physiol. 272, C853-C859 (1997).
117. Kent G, Iles R, Bear CE et al. Lung disease in mice with cystic fibrosis. J. Clin. Invest. 100, 3060-3069 (1997).
118. Bruscia E, Price JE, Cheng E-C et al. Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proc. Natl Acad. Sci. USA 103, 2965-2970 (2006).
119. Bruscia E, Ziegler EC, Price JE, Weiner S, Egan ME, Krause DS. Engraftment of donor-derived epithelial cells in multiple organs following bone marrow transplantation into newborn mice. Stem Cells 24, 2299-2308 (2006).
120. Johnson L, Olsen J, Sarkadi B, Moore K, Swanstrom R, Boucher R. Efficiency of gene transfer for testoration of normal airway epithelial function in cystic fibrosis. Nat. Genet. 2, 21-25 (1992).
121. Farmen SL, Karp PH, Ng P et al. Gene transfer of CFTR to airway epithelia: low levels of expression are sufficient to correct Cr transport and overexpression can generate basolateral CFTR. Am. J. Physiol Lung Cell. Mol. Physiol. 289, L123-L1130 (2005).
122. Johnson LG, Boyles SE, Wilson J, Boucher RC. Normalization of raised sodium absorption and raised calcium-mediated chloride secretion by adenovirus-mediated expression of cystic fibrosis transmembrane conductance regulator in primary human cystic fibrosis airway epithelial cells. J Clin. Invest. 95, 1377-1382 (1995).
123. Goldman MJ, Yang Y, Wilson JM. Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect. Nat. Genet. 9, 126-131 (1995).
124. Weiss DJ, Berberich MA, Borok Z et al. Adult stem cells, lung biology, and lung disease. NHLBI/Cystic Fibrosis Foundation Workshop. Proc. Am. Thorac. Soc. 3, 193-207 (2006).
125. Spees JL, Olson SD, Ylostalo J et al. Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells fiorn bone marrow stroma. Proc. Natl. Acad Sci. USA 100, 2397-2402 (2003).
126. Shu C, Li TY, Tsang LL et al. Differentiation of adult rat bone marrow stem cells into epithelial progenitor cells in culture. Cell Biol. Int. 30, 823-828 (2006).
127. Wang G, Bunnell BA, Painter RG et al. Adult stem cells fiom bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc. Natl Acad. Sci. USA 102, 186-191 (2005).
128. Viswanathan A, Painter RG, Lanson NA Jr, Wang G. Functional expression of N-formyl peptide receptors in human bone marrow-derived mesenchymal stem cells. Stem Cells 25, 1263-1269 (2007).
129. Phinney DG. Biochemical heterogeneity of mesenchymal stem cell populations: dues to their therapeutic efficacy. Cell Cycle 6, 2884-2889 (2007).
130. Hung SC, Pochampally RR, Chen SC, Hsu SC, Prockop DJ. Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells 25, 2363-2370 (2007).
131. Inoue Y, Iriyama A, Ueno S et al. Subretinal transplantation of bone marrow mesenchymal stem cells delays retinal degeneration in the RCS rat model of retinal degeneration. Exp. Eye Res. 85, 234-241 (2007).
132. Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am. J. Physiol. Renal Physiol. 289, F31-F42 (2005).
133. Mei SH, McCarter SD, Deng Y, Parker CH, Liles WC, Stewart DJ. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med. 4, e269 (2007).
134. Ortiz LA. Dutreil M, Fattman C et al. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc. Natl Acad. Sci. USA 104, 11002-11007 (2007).
135. Gupta N, Su X. Popov B, Lee JW, Serikoy V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol, 179, 1855-1863 (2007).
136. Uccelli A. Pistoia V, Moretta L. Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol. 28, 219-226 (2007).
137. Knudtzon S. In vitro growth of granulocytic colonies from circulating cells in human cord blood. Blood 43, 357-361 (1974).
138. Gluckman E, Broxmeyer HA, Auerbach AD et al. Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. N. Engl. J. Med. 321, 1174-1178 (1989).
139. Lee MW, Choi J, Yang MS et al. Mesenchymal stem cells from cryopreserved human umbilical cord blood. Biochem. Biophys. Res. Commun. 320, 273-278 (2004).
140. van de Ven C, Collins D, Bradley MB, Morris E, Cairo MS. The potential of umbilical cord blood multipotent stem cells for nonhematopoietic tissue and cell regeneration. Exp. Hematol. 35, 1753-1765 (2007).
141. Kamolz LP, Kolbus A, Wick N et al. Cultured human epithelium: human umbilical cord blood stem cells differentiate into keratinocytes under in vitro conditions. Burns 32, 16-19 (2006).
142. Dai Y, Li J, Li J et al. Skin epithelial cells in mice from umbilical cord blood mesenchymal stem cells. Burns 33, 418-428 (2007).
143. Berger MJ, Adams SD, Tigges BM et al. Differentiation of umbilical cord blood-derived multilineage progenitor cells into respiratory epithelial cells. Cytotherapy 8, 480-487 (2006).
144. Sueblinvong V, Loi R, Eisenhauer PL et al. Derivation of lung epithelium from human cord blood-derived mesenchymal stem cells. Am. J. Respir. Crit. Care Med. 177(7), 701-711 (2008).
145. Son BR, Marquez-Curtis LA, Kucia M 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 24, 1254-1264 (2006).
146. Wobus AM, Boheler KR. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol. Rev. 85, 635-678 (2005).
147. Ben-Yosef D, Malcov M, Eiges R. PGD-derived human embryonic stem cell lines as a powerful tool for the study of human genetic disorders. Mol. Cell. Endocrinol. 282, 153-158 (2008).
148. Sermon K, Van Steirteghem A, Liebaers, I. Preimplantation genetic diagnosis. Lancet 363, 1633-1641 (2004).
149. Mateizel I, De Temmerman N, Ullmann U et al. Derivation of human embryonic stem cell lines from embryos obtained after IVF and after PGD for monogenic disorders. Hum. Reprod. 21, 503-511 (2006).
150. Pickering SJ, Minger SL, Patel M et al. Generation of a human embryonic stem cell line encoding the cystic fibrosis mutation AF508, using preimplantation genetic diagnosis. Reprod. Biomed. Online 10, 390-397 (2005).
151. Rippon HJ, Polak JM, Qin M, Bishop AE. Derivation of distal lung epithelial progenitors from routine embryonic stem cells using a novel three-step differentiation protocol. Stem Cells 24, 1389-1398 (2006).
152. Wang D, Haviland DL, Bums AR, Zsigmond E, Wetsel RA. A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells. Proc. Natl Acad Sci. USA 104, 4449-4454 (2007).
153. Coraux C, Nawrocki-Raby B, Hinnrasky J et al. Embryonic stem cells generate airway epithelial tissue. Am. J. Respir. Cell Mol. Biol. 32, 87-92 (2005).
154. Van Vranken BE, Romanska HM, Polak JM, Rippon HJ, Shannon JM, Bishop AE. Coculture of embryonic stem cells with pulmonary mesenchyme: a microenvironment that promotes differentiation of pulmonary epithelium. Tissue Eng. 11, 1177-1187 (2005).
155. Denham M, Cole TJ, Mollard R. Embryonic stem cells form glandular structures and express surfactant protein C following culture with dissociated fetal respiratory tissue. Am. J. Physiol. Lung Cell. Mol. Physiol. 290, L1210-L1215 (2006).
156. Denham M, Conley BJ, Olsson F, Gulluyan L, Cole T, Mollard R. A murine respiratory inducing niche displays variable efficiency across human and mouse embryonic stem cell species. Am J Physiol. Lung Cell. Mol. Physiol. 292(5), L1241-L1247 (2007).
157. Sampaolesi M, Blot S, D'Antona G et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 444, 574-579 (2006).
158. Cavazzana-Calvo M, Fischer A. Gene therapy for severe combined immunodeficiency: are we there yet? J. Clin. Invest. 117, 1456-1465 (2007).
159. Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant. 30, 215-222 (2002).
160. Horwitz EM, Gordon PL, Koo WK et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: implications for cell therapy of bone. Proc. Natl Acad. Sci. USA 99, 8932-8937 (2002).
161. Krampera M, Cosmi L, Angeli R et al. Role for interferon-γ in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 24, 386-398 (2006).
162. Frank MH, Sayegh MH. Immunomodulatory functions of mesenchymal stem cells. Lancet 363, 1411-1412 (2004).
163. Le Blanc K. Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 5, 485-489 (2003).