A perspective on bioactive cell microencapsulation

BioDrugs

Volumn 26, Issue 5, 2012, Pages 283-301

  Acarregui, Argia ^a,b   Murua, Ainhoa ^a,b   Pedraz, Jos L ^a,b   Orive, Gorka ^a,b   Hernndez, Rosa M ^a,b  

^a UNIVERSITY OF THE BASQUE COUNTRY UPV EHU   (Spain)

^b BIOMATERIALES Y NANOMEDICINA CIBER BBN   (Spain)

Author keywords

Alginate; Cardiovascular disorders; Chitosan; CNS disorders; Collagen; Diabetes mellitus; Drug delivery systems; Encapsulated cell therapy; Liver disorders; Polymers.

Indexed keywords

AGAROSE; ALGINIC ACID; CELLULOSE SULFATE; CHITOSAN; COLLAGEN; GELATIN; HYALURONIC ACID; MACROGOL; POLY(N ISOPROPYLACRYLAMIDE);

BIOCOMPATIBILITY; CARDIOVASCULAR DISEASE; CELL ENCAPSULATION; CENTRAL NERVOUS SYSTEM DISEASE; DIABETES MELLITUS; DRUG DELIVERY SYSTEM; GEL; HUMAN; LIVER DISEASE; MECHANICAL INTEGRITY; MECHANICS; MICROENCAPSULATION; MOLECULAR STABILITY; NONHUMAN; PERMEABILITY; PRIORITY JOURNAL; REVIEW;

ANIMALS; BIOCOMPATIBLE MATERIALS; BIOTECHNOLOGY; CAPSULES; CELL TRANSPLANTATION; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; HUMANS; TISSUE THERAPY;

EID: 84866133341     PISSN: 11738804     EISSN: 1179190X     Source Type: Journal    
DOI: 10.2165/11632640-000000000-00000     Document Type: Review

References (255)

1. Balmayor ER, Azevedo HS, Reis RL. Controlled delivery systems: From pharmaceuticals to cells and genes. Pharm Res 2011; 28: 1241-58
2. Nafea EH, Poole-Warren AM, Martens PJ. Immunoisolating semi-permeable membranes for cell encapsulation: Focus on hydrogels. J Control Release 2011; 154: 110-22
3. Hernandez RM, Orive G, Murua A, et al. Microcapsules and microcarriers for in situ cell delivery. Adv Drug Deliv Rev 2010; 62: 711-30
4. Hunt NC, Grover LM. Cell encapsulation using biopolymer gels for regenerative medicine. Biotechnol Lett 2010; 32: 733-42
5. Chang TM. Therapeutic applications of polymeric artificial cells. Nat Rev Drug Discov 2005; 4: 221-35
6. Moskalenko V, Ulrichs K, Kerscher A, et al. Preoperative evaluation of microencapsulated human parathyroid tissue aids selection of the optimal bioartificial graft for human parathyroid allotransplantation. Transpl Int 2007; 20: 688-96
7. Wen J, Vargas AG, Ofosu FA, et al. Sustained and therapeutic levels of human factor IX in hemophilia B mice implanted with microcapsules: Key role of encapsulated cells. J Gene Med 2006; 8: 362-9
8. Wen J, Xu N, Li A, et al. Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. J Gene Med 2007; 9: 1002-10
9. Murua A, Orive G, Hernandez RM, et al. Xenogeneic transplantation of erythropoietin-secreting cells immobilized in microcapsules using transient immunosuppression. J Control Release 2009; 137: 174-8
10. Chang PL, Van Raamsdonk JM, Hortelano G, et al. The in vivo delivery of heterologous proteins by microencapsulated recombinant cells. Trends Biotechnol 1999; 17: 78-83
11. Cheng WT, Chen BC, Chiou ST, et al. Use of nonautologous microencapsulated fibroblasts in growth hormone gene therapy to improve growth of midget swine. Hum Gene Ther 1998; 9: 1995-2003
12. Mei J, Sgroi A, Mai G, et al. Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice. Cell Transplant 2009; 18: 101-10
13. Skinner SJ, Geaney MS, Lin H, et al. Encapsulated living choroid plexus cells: Eotential long-term treatments for central nervous system disease and trauma. J Neural Eng 2009; 6: 065001
14. Borlongan CV, Thanos CG, Skinner SJ, et al. Transplants of encapsulated rat choroid plexus cells exert neuroprotection in a rodent model of Huntington's disease. Cell Transplant 2008; 16: 987-92
15. Vaithilingam V, Kollarikova G, Qi M, et al. Effect of prolonged gelling time on the intrinsic properties of barium alginate microcapsules and its biocompatibility. J Microencapsul 2011; 28: 499-507
16. Salmons B, Brandtner EM, Hettrich K, et al. Encapsulated cells to focus the metabolic activation of anticancer drugs. Curr Opin Mol Ther 2010; 12: 450-60
17. Al Kindi AH, Asenjo JF, Ge Y, et al. Microencapsulation to reduce mechanical loss of microspheres: Implications in myocardial cell therapy. Eur J Cardiothorac Surg 2011; 39: 241-7
18. Murua A, Portero A, Orive G, et al. Cell microencapsulation technology: Towards clinical application. J Control Release 2008; 132: 76-83
19. Qi M, Strand BL, Morch Y, et al. Encapsulation of human islets in novel inhomogeneous alginate-ca2+/ba2+ microbeads: In vitro and in vivo function. Artif Cells Blood Substit Immobil Biotechnol 2008; 36: 403-20
20. Giovagnoli S, Blasi P, Luca G, et al. Bioactive long-term release from biodegradable microspheres preserves implanted ALG-PLO-ALG microcapsules from in vivo response to purified alginate. Pharm Res 2010; 27: 285-95
21. Murua A, Orive G, Hernandez RM, et al. Cryopreservation based on freezing protocols for the long-term storage of microencapsulated myoblasts. Biomaterials 2009; 30: 3495-501
22. Lim F, Sun AM. Microencapsulated islets as bioartificial endocrine pancreas. Science 1980; 210: 908-10
23. Paul A, Cantor A, Shum-Tim D, et al. Superior cell delivery features of genipin crosslinked polymeric microcapsules: Ereparation, in vitro characterization and pro-angiogenic applications using human adipose stem cells. Mol Biotechnol 2011; 48: 116-27
24. Marsich E, Borgogna M, Donati I, et al. Alginate/lactose-modified chitosan hydrogels: A bioactive biomaterial for chondrocyte encapsulation. J Biomed Mater Res A 2008; 84: 364-76
25. Donati I, Haug IJ, Scarpa T, et al. Synergistic effects in semidilute mixed solutions of alginate and lactose-modified chitosan (chitlac). Biomacromolecules 2007; 8: 957-62
26. Orive G, Bartkowiak A, Lisiecki S, et al. Biocompatible oligochitosans as cationic modifiers of alginate/Ca microcapsules. J Biomed Mater Res B Appl Biomater 2005; 74: 429-39
27. De Castro M, Orive G, Hernandez RM, et al. Biocompatibility and in vivo evaluation of oligochitosans as cationic modifiers of alginate/Ca microcapsules. J Biomed Mater Res A 2009; 91: 1119-30
28. Rokstad AM, Brekke OL, Steinkjer B, et al. Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model. Acta Biomater 2011; 7: 2566-78
29. Dandoy P, Meunier CF, Michiels C, et al. Hybrid shell engineering of animal cells for immune protections and regulation of drug delivery: Towards the design of ''artificial organs''. PLoS One 2011; 6: E20983
30. Leung A, Trau M, Nielsen LK. Assembly of multilayer PSS/PAH membrane on coherent alginate/PLO microcapsule for long-term graft transplantation. J Biomed Mater Res A 2009; 88: 226-37
31. Zhi ZL, Liu B, Jones PM, et al. Polysaccharide multilayer nanoencapsulation of insulin-producing beta-cells grown as pseudoislets for potential cellular delivery of insulin. Biomacromolecules 2010; 11: 610-6
32. Kunze A, Giugliano M, Valero A, et al. Micropatterning neural cell cultures in 3D with a multi-layered scaffold. Biomaterials 2011; 32: 2088-98
33. Ponce S, Orive G, Hernandez R, et al. Chemistry and the biological response against immunoisolating alginate-polycation capsules of different composition. Biomaterials 2006; 27: 4831-9
34. Tam SK, Bilodeau S, Dusseault J, et al. Biocompatibility and physicochemical characteristics of alginate-polycation microcapsules. Acta Biomater 2011; 7: 1683-92
35. Murua A, de Castro M, Orive G, et al. In vitro characterization and in vivo functionality of erythropoietin-secreting cells immobilized in alginate-poly- L-lysine-alginate microcapsules. Biomacromolecules 2007; 8: 3302-7
36. Calafiore R. Alginate microcapsules for pancreatic islet cell graft immunoprotection: struggle and progress towards the final cure for type 1 diabetes mellitus. Expert Opin Biol Ther 2003; 3: 201-5
37. Franco CL, Price J, West JL. Development and optimization of a dualphotoinitiator, emulsion-based technique for rapid generation of cell-laden hydrogel microspheres. Acta Biomater 2011; 7: 3267-76
38. Ji XH, Cheng W, Guo F, et al. On-demand preparation of quantum dot-encoded microparticles using a droplet microfluidic system. Lab Chip 2011; 11: 2561-8
39. Domachuk P, Tsioris K, Omenetto FG, et al. Bio-microfluidics: Biomaterials and biomimetic designs. Adv Mater 2010; 22: 249-60
40. Rosellini E, Vozzi G, Barbani N, et al. Three-dimensional microfabricated scaffolds with cardiac extracellular matrix-like architecture. Int J Artif Organs 2010; 33: 885-94
41. Ye Z, Mahato RI. Emerging trends in cell-based therapies: Ereface. Adv Drug Deliv Rev 2008; 60: 89-90
42. Lee KY, Mooney DJ. Alginate: Eroperties and biomedical applications. Prog Polym Sci 2012; 37: 106-26
43. Wu TJ, Huang HH, Hsu YM, et al. A novel method of encapsulating and cultivating adherent mammalian cells within collagen microcarriers. Biotechnol Bioeng 2007; 98: 578-85
44. Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater 2011; 23: H41-56
45. Baruch L, Machluf M. Alginate-chitosan complex coacervation for cell encapsulation: Effect on mechanical properties and on long-term viability. Biopolymers 2006; 82: 570-9
46. Sakai S, Hashimoto I, Tanaka S, et al. Small agarose microcapsules with cellenclosing hollow core for cell therapy: Transplantation of ifosfamideactivating cells to the mice with preestablished subcutaneous tumor. Cell Transplant 2009; 18: 933-9
47. Sakai S, Ito S, Kawakami K. Calcium alginate microcapsules with spherical liquid cores templated by gelatin microparticles for mass production of multicellular spheroids. Acta Biomater 2010; 6: 3132-7
48. Sakai S, Kawakami K. Both ionically and enzymatically crosslinkable alginate- tyramine conjugate as materials for cell encapsulation. J Biomed Mater Res A 2008; 85: 345-51
49. Santos E, Zarate J, Orive G, et al. Biomaterials in cell microencapsulation. Adv Exp Med Biol 2010; 670: 5-21
50. Orive G, Tam SK, Pedraz JL, et al. Biocompatibility of alginate-poly-L-lysine microcapsules for cell therapy. Biomaterials 2006; 27: 3691-700
51. Braccini I, Perez S. Molecular basis of C(2+)-induced gelation in alginates and pectins: The egg-box model revisited. Biomacromolecules 2001; 2: 1089-96
52. Donati I, Holtan S, Morch YA, et al. New hypothesis on the role of alternating sequences in calcium-alginate gels. Biomacromolecules 2005; 6: 1031-40
53. Morch YA, Donati I, Strand BL, et al. Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads. Biomacromolecules 2006; 7: 1471-80
54. Orive G, Hernandez RM, Rodriguez Gascon A, et al. History, challenges and perspectives of cell microencapsulation. Trends Biotechnol 2004; 22: 87-92
55. Drury JL, Dennis RG, Mooney DJ. The tensile properties of alginate hydrogels. Biomaterials 2004; 25: 3187-99
56. George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - a review. JControlRelease 2006; 114: 1-14
57. Chan G, Mooney DJ. New materials for tissue engineering: Towards greater control over the biological response. Trends Biotechnol 2008; 26: 382-92
58. Augst AD, Kong HJ, Mooney DJ. Alginate hydrogels as biomaterials. Macromol Biosci 2006; 6: 623-33
59. Smetana Jr K. Cell biology of hydrogels. Biomaterials 1993; 14: 1046-50
60. Rowley JA, Madlambayan G, Mooney DJ. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 1999; 20: 45-53
61. Boontheekul T, Kong HJ, Hsiong SX, et al. Quantifying the relation between bond number and myoblast proliferation. Faraday Discuss 2008; 139: 53-70; discussion 105-28, 419-20
62. Comisar WA, Kazmers NH, Mooney DJ, et al. Engineering RGD nanopatterned hydrogels to control preosteoblast behavior: A combined computational and experimental approach. Biomaterials 2007; 28: 4409-17
63. Kong HJ, Boontheekul T, Mooney DJ. Quantifying the relation between adhesion ligand-receptor bond formation and cell phenotype. Proc Natl Acad Sci U S A 2006; 103: 18534-9
64. Huebsch ND, Mooney DJ. Fluorescent resonance energy transfer: A tool for probing molecular cell-biomaterial interactions in three dimensions. Biomaterials 2007; 28: 2424-37
65. Alsberg E, Anderson KW, Albeiruti A, et al. Cell-interactive alginate hydrogels for bone tissue engineering. J Dent Res 2001; 80: 2025-9
66. Dhoot NO, Tobias CA, Fischer I, et al. Peptide-modified alginate surfaces as a growth permissive substrate for neurite outgrowth. J Biomed Mater Res A 2004; 71: 191-200
67. Mazzitelli S, Luca G, Mancuso F, et al. Production and characterization of engineered alginate-based microparticles containing ECM powder for cell/tissue engineering applications. Acta Biomater 2011; 7: 1050-62
68. Orive G, De Castro M, Kong HJ, et al. Bioactive cell-hydrogel microcapsules for cell-based drug delivery. J Control Release 2009; 135: 203-10
69. Boontheekul T, Kong HJ, Mooney DJ. Controlling alginate gel degradation utilizing partial oxidation and bimodal molecular weight distribution. Biomaterials 2005; 26: 2455-65
70. Silva EA, Mooney DJ. Spatiotemporal control of vascular endothelial growth factor delivery from injectable hydrogels enhances angiogenesis. J Thromb Haemost 2007; 5: 590-8
71. Bouhadir KH, Lee KY, Alsberg E, et al. Degradation of partially oxidized alginate and its potential application for tissue engineering. Biotechnol Prog 2001; 17: 945-50
72. Zhou H, Xu HH. The fast release of stem cells from alginate-fibrin microbeads in injectable scaffolds for bone tissue engineering. Biomaterials 2011; 32: 7503-13
73. Rokstad AM, Donati I, Borgogna M, et al. Cell-compatible covalently reinforced beads obtained from a chemoenzymatically engineered alginate. Biomaterials 2006; 27: 4726-37
74. Gattas-AsfuraKM, Fraker CA, Stabler CL. Covalent stabilization of alginate hydrogel beads via Staudinger ligation: Assessment of poly(ethylene glycol) and alginate cross-linkers. J Biomed Mater Res A 2011; 99: 47-57
75. Rosenblatt J, Devereux B, Wallace DG. Injectable collagen as a pH-sensitive hydrogel. Biomaterials 1994; 15: 985-95
76. Senuma Y, Franceschin S, Hilborn JG, et al. Bioresorbable microspheres by spinning disk atomization as injectable cell carrier: From preparation to in vitro evaluation. Biomaterials 2000; 21: 1135-44
77. Lee M, Lo AC, Cheung PT, et al. Drug carrier systems based on collagenalginate composite structures for improving the performance of GDNFsecreting HEK293 cells. Biomaterials 2009; 30: 1214-21
78. Ananta M, Brown RA, Mudera V. A rapid fabricated living dermal equivalent for skin tissue engineering: An in vivo evaluation in an acute wound model. Tissue Eng Part A 2012; 18: 353-61
79. Zhang Y, Wang F, Chen J, et al. Bone marrow-derived mesenchymal stem cells versus bone marrow nucleated cells in the treatment of chondral defects. Int Orthop 2012; 36: 1079-86
80. Bitar M, Salih V, Brown RA, et al. Effect of multiple unconfined compression on cellular dense collagen scaffolds for bone tissue engineering. J Mater Sci Mater Med 2007; 18: 237-44
81. Flanagan TC, Wilkins B, Black A, et al. A collagen-glycosaminoglycan coculture model for heart valve tissue engineering applications. Biomaterials 2006; 27: 2233-46
82. MurrayMM,ForsytheB,ChenF, et al. The effect of thrombin onACLfibroblast interactions with collagen hydrogels. J Orthop Res 2006; 24: 508-15
83. Chenite A, Chaput C, Wang D, et al. Novel injectable neutral solutions of chitosan form biodegradable gels in situ. Biomaterials 2000; 21: 2155-61
84. Monteiro Jr OA, Airoldi C. Some studies of crosslinking chitosanglutaraldehyde interaction in a homogeneous system. Int J Biol Macromol 1999; 26: 119-28
85. Zielinski BA, Aebischer P. Chitosan as a matrix for mammalian cell encapsulation. Biomaterials 1994; 15: 1049-56
86. Dang JM, Leong KW. Myogenic induction of aligned mesenchymal stem cell sheets by culture on thermally responsive electrospun nanofibers. Adv Mater 2007; 19: 2775-9
87. Dang JM, Sun DD, Shin-Ya Y, et al. Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells. Biomaterials 2006; 27: 406-18
88. Hayami JW, Waldman SD, Amsden BG. A photocurable hydrogel/elastomer composite scaffold with bi-continuous morphology for cell encapsulation. Macromol Biosci 2011; 11: 1672-83
89. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev 2001; 101: 1869-79
90. Buckley CT, Thorpe SD, O'Brien FJ, et al. The effect of concentration, thermal history and cell seeding density on the initial mechanical properties of agarose hydrogels. J Mech Behav Biomed Mater 2009; 2: 512-21
91. Luo D, Pullela SR, Marquez M, et al. Cell encapsules with tunable transport and mechanical properties. Biomicrofluidics 2007; 1: 34102
92. Sakai S, Hashimoto I, Kawakami K. Agarose-gelatin conjugate membrane enhances proliferation of adherent cells enclosed in hollow-core microcapsules. J Biomater Sci Polym Ed 2008; 19: 937-44
93. Sakai S, Hashimoto I, Kawakami K. Production of cell-enclosing hollowcore agarose microcapsules via jetting in water-immiscible liquid paraffin and formation of embryoid body-like spherical tissues from mouse ES cells enclosed within these microcapsules. Biotechnol Bioeng 2008; 99: 235-43
94. Gazda LS, Vinerean HV, Laramore MA, et al. Encapsulation of porcine islets permits extended culture time and insulin independence in spontaneously diabetic BB rats. Cell Transplant 2007; 16: 609-20
95. Wosnick JH, Shoichet MS. Three-dimensional chemical patterning of transparent hydrogels. Chem Mater 2008; 20: 55-60
96. Uludag H, De Vos P, Tresco PA. Technology of mammalian cell encapsulation. Adv Drug Deliv Rev 2000; 42: 29-64
97. Schmaljohann D. Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 2006; 58: 1655-70
98. Chaterji S, Kwon IK, Park K. Smart polymeric gels: Redefining the limits of biomedical devices. Prog Polym Sci 2007; 32: 1083-122
99. Kim MR, Jeong JH, Park TG. Swelling induced detachment of chondrocytes using RGD-modified poly(N-isopropylacrylamide) hydrogel beads. Biotechnol Prog 2002; 18: 495-500
100. Lu HF, Targonsky ED, Wheeler MB, et al. Thermally induced gelable polymer networks for living cell encapsulation. Biotechnol Bioeng 2007; 96: 146-55
101. Sa-Lima H, Tuzlakoglu K, Mano JF, et al. Thermoresponsive poly(Nisopropylacrylamide)- g-methylcellulose hydrogel as a three-dimensional extracellular matrix for cartilage-engineered applications. J Biomed Mater Res A 2011; 98: 596-603
102. Gó mez-Guillén MC, Pérez-Mateos M, Gó mez-Estaca J, et al. Fish gelatin: A renewable material for developing active biodegradable films. Trends Food Sci Technol 2009; 20: 3-16
103. Payne RG, Yaszemski MJ, Yasko AW, et al. Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations. Part 1. Encapsulation of marrow stromal osteoblasts in surface crosslinked gelatin microparticles. Biomaterials 2002; 23: 4359-71
104. Huang S, Deng T, Wang Y, et al. Multifunctional implantable particles for skin tissue regeneration: Ereparation, characterization, in vitro and in vivo studies. Acta Biomater 2008; 4: 1057-66
105. Stover NP, Watts RL. Spheramine for treatment of Parkinson's disease. Neurotherapeutics 2008; 5: 252-9
106. Huss FR, Junker JP, Johnson H, et al. Macroporous gelatine spheres as culture substrate, transplantation vehicle, and biodegradable scaffold for guided regeneration of soft tissues: In vivo study in nude mice. J Plast Reconstr Aesthet Surg 2007; 60: 543-55
107. Gustafson CJ, Birgisson A, Junker J, et al. Employing human keratinocytes cultured on macroporous gelatin spheres to treat full thickness-wounds: An in vivo study on athymic rats. Burns 2007; 33: 726-35
108. Sommar P, Pettersson S, Ness C, et al. Engineering three-dimensional cartilage- and bone-like tissues using human dermal fibroblasts and macroporous gelatine microcarriers. J Plast Reconstr Aesthet Surg 2010; 63: 1036-46
109. Nuttelman CR, Kloxin AM, Anseth KS. Temporal changes in peg hydrogel structure influence human mesenchymal stem cell proliferation and matrix mineralization. Adv Exp Med Biol 2006; 585: 135-49
110. Adelow C, Segura T, Hubbell JA, et al. The effect of enzymatically degradable poly(ethylene glycol) hydrogels on smooth muscle cell phenotype. Biomaterials 2008; 29: 314-26
111. HallKK, Gattas-Asfura KM, Stabler CL. Microencapsulation of islets within alginate/poly(ethylene glycol) gels cross-linked via Staudinger ligation. Acta Biomater 2011; 7: 614-24
112. Peroglio M, Grad S, Mortisen D, et al. Injectable thermoreversible hyaluronan- based hydrogels for nucleus pulposus cell encapsulation. Eur Spine J. Epub 2011 Aug 27; DOI 10.1007/s00586-011-1976-2
113. Pelegrin M, Marin M, Noel D, et al. Systemic long-term delivery of antibodies in immunocompetent animals using cellulose sulphate capsules containing antibody-producing cells. Gene Ther 1998; 5: 828-34
114. Stadlbauer V, Stiegler PB, Schaffellner S, et al. Morphological and functional characterization of a pancreatic beta-cell line microencapsulated in sodium cellulose sulfate/poly(diallyldimethylammonium chloride). Xenotransplantation 2006; 13: 337-44
115. Stiegler P, Matzi V, Pierer E, et al. Creation of a prevascularized site for cell transplantation in rats. Xenotransplantation 2010; 17: 379-90
116. Leung A, Nielsen LK, Trau M, et al. Tissue transplantation by stealth: Coherent alginate microcapsules for immunoisolation. Biochem Eng J 2010; 48: 337-47
117. de Vos P, Bucko M, Gemeiner P, et al. Multiscale requirements for bioencapsulation in medicine and biotechnology. Biomaterials 2009; 30: 2559-70
118. Kulseng B, Thu B, Espevik T, et al. Alginate polylysine microcapsules as immune barrier: Eermeability of cytokines and immunoglobulins over the capsule membrane. Cell Transplant 1997; 6: 387-94
119. DembczynskiR, Jankowski T. Determination of pore diameter and molecular weight cut-off of hydrogel-membrane liquid-core capsules for immunoisolation. J Biomater Sci Polym Ed 2001; 12: 1051-8
120. de Haan BJ, Faas MM, de Vos P. Factors influencing insulin secretion from encapsulated islets. Cell Transplant 2003; 12: 617-25
121. Schneider S, Feilen PJ, Slotty V, et al. Multilayer capsules: A promising microencapsulation system for transplantation of pancreatic islets. Biomaterials 2001; 22: 1961-70
122. Tun T, Inoue K, Hayashi H, et al. A newly developed three-layer agarose microcapsule for a promising biohybrid artificial pancreas: Rat to mouse xenotransplantation. Cell Transplant 1996; 5: S59-63
123. Weber LM, Cheung CY, Anseth KS. Multifunctional pancreatic islet encapsulation barriers achieved via multilayer PEG hydrogels. Cell Transplant 2008; 16: 1049-57
124. Schmidt JJ, Rowley J, Kong HJ. Hydrogels used for cell-based drug delivery. J Biomed Mater Res A 2008; 87: 1113-22
125. Orive G, Hernandez RM, Gascon AR, et al. Development and optimisation of alginate-PMCG-alginate microcapsules for cell immobilisation. Int J Pharm 2003; 259: 57-68
126. Darrabie MD, Kendall Jr WF, Opara EC. Characteristics of Poly-L-Ornithine- coated alginate microcapsules. Biomaterials 2005; 26: 6846-52
127. Thanos CG, Bintz BE, Emerich DF. Stability of alginate-polyornithine microcapsules is profoundly dependent on the site of transplantation. J Biomed Mater Res A 2007; 81: 1-11
128. Fontes A, Fernandes HP, de Thomaz AA, et al. Measuring electrical and mechanical properties of red blood cells with double optical tweezers. J Biomed Opt 2008; 13: 014001
129. Hochmuth RM. Micropipette aspiration of living cells. J Biomech 2000; 33: 15-22
130. Dulinska I, Targosz M, Strojny W, et al. Stiffness of normal and pathological erythrocytes studied by means of atomic force microscopy. J Biochem Biophys Methods 2006; 66: 1-11
131. Bausch AR, Moller W, Sackmann E. Measurement of local viscoelasticity and forces in living cells by magnetic tweezers. Biophys J 1999; 76: 573-9
132. Kim K, Liu X, Zhang Y, et al. Elastic and viscoelastic characterization of microcapsules for drug delivery using a force-feedback MEMS microgripper. Biomed Microdevices 2009; 11: 421-7
133. Sugiura S, Oda T, Izumida Y, et al. Size control of calcium alginate beads containing living cells usingmicro-nozzle array. Biomaterials 2005; 26: 3327-31
134. Sugiura S, Oda T, Aoyagi Y, et al. Microfabricated airflow nozzle for microencapsulation of living cells into 150 micrometer microcapsules. Biomed Microdevices 2007; 9: 91-9
135. Robitaille R, Leblond FA, Bourgeois Y, et al. Studies on small (<350 microm) alginate-poly-L-lysine microcapsules. V. Determination of carbohydrate and protein permeation through microcapsules by reverse-size exclusion chromatography. J Biomed Mater Res 2000; 50: 420-7
136. Canaple L, Rehor A, Hunkeler D. Improving cell encapsulation through size control. J Biomater Sci Polym Ed 2002; 13: 783-96
137. Chicheportiche D, Reach G. In vitro kinetics of insulin release by microencapsulated rat islets: Effect of the size of the microcapsules. Diabetologia 1988; 31: 54-7
138. Beck J, Angus R, Madsen B, et al. Islet encapsulation: strategies to enhance islet cell functions. Tissue Eng 2007; 13: 589-99
139. Zhang X, Xie Y, Koh CG, et al. A novel 3-D model for cell culture and tissue engineering. Biomed Microdevices 2009; 11: 795-9
140. Spuch C, Antequera D, Portero A, et al. The effect of encapsulated VEGFsecreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer's disease. Biomaterials 2010; 31: 5608-18
141. Santos E, Orive G, Calvo A, et al. Optimization of 100mum alginate-poly-llysine- alginate capsules for intravitreous administration. J Control Release 2012; 158: 443-50
142. Kontturi LS, Yliperttula M, Toivanen P, et al. A laboratory-scale device for the straightforward production of uniform, small sized cell microcapsules with long-term cell viability. J Control Release 2011; 152: 376-81
143. Hong J, deMello AJ, Jayasinghe SN. Bio-electrospraying and droplet-based microfluidics: Control of cell numbers within living residues. Biomed Mater 2010; 5: 21001
144. Wang W, LiuX,Xie Y, et al.Microencapsulation using natural polysaccharides for drug delivery and cell implantation. J Mater Chem 2006; 16: 3252-67
145. Orive G, Carcaboso AM, Hernandez RM, et al. Biocompatibility evaluation of different alginates and alginate-based microcapsules. Biomacromolecules 2005; 6: 927-31
146. Williams DF. On the mechanisms of biocompatibility. Biomaterials 2008; 29: 2941-53
147. Stark D, KornmannH, Munch T, et al. Novel type of in situ extraction: Use of solvent containing microcapsules for the bioconversion of 2-phenylethanol from L-phenylalanine by Saccharomyces cerevisiae. Biotechnol Bioeng 2003; 83: 376-85
148. JunterGA, Jouenne T. Immobilized viablemicrobial cells: Fromthe process to the proteome em leader or the cart before the horse. BiotechnolAdv 2004; 22: 633-58
149. Leinfelder U, Brunnenmeier F, Cramer H, et al. A highly sensitive cell assay for validation of purification regimes of alginates. Biomaterials 2003; 24: 4161-72
150. de Haan BJ, Rossi A, Faas MM, et al. Structural surface changes and inflammatory responses against alginate-based microcapsules after exposure to human peritoneal fluid. J Biomed Mater Res A 2011; 98: 394-403
151. Tam SK, Dusseault J, Bilodeau S, et al. Factors influencing alginate gel biocompatibility. J Biomed Mater Res A 2011; 98: 40-52
152. Bunger CM, Tiefenbach B, Jahnke A, et al. Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids. Biomaterials 2005; 26: 2353-60
153. Murua A,Herran E, Orive G, et al. Design of a composite drug delivery system to prolong functionality of cell-based scaffolds. Int J Pharm 2011; 407: 142-50
154. Baruch L, Benny O, Gilert A, et al. Alginate-PLL cell encapsulation system Co-entrapping PLGA-microspheres for the continuous release of antiinflammatory drugs. Biomed Microdevices. Epub 2009 Jun 11; DOI 10.1007/s10544-009-9327-3
155. Omer A, Keegan M, Czismadia E, et al. Macrophage depletion improves survival of porcine neonatal pancreatic cell clusters contained in alginate macrocapsules transplanted into rats. Xenotransplantation 2003; 10: 240-51
156. Barnett BP, Arepally A, Stuber M, et al. Synthesis of magnetic resonance-, X-ray- and ultrasound-visible alginate microcapsules for immunoisolation and noninvasive imaging of cellular therapeutics. Nat Protoc 2011; 6: 1142-51
157. Link TW, Woodrum D, Gilson WD, et al. MR-guided portal vein delivery and monitoring of magnetocapsules: Assessment of physiologic effects on the liver. J Vasc Interv Radiol 2011; 22: 1335-40
158. Catena R, Santos E, Orive G, et al. Improvement of the monitoring and biosafety of encapsulated cells using the SFGNESTGL triple reporter system. J Control Release 2010; 146: 93-8
159. Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 2000; 343: 230-8
160. de Vos P, Faas MM, Strand B, et al. Alginate-based microcapsules for immunoisolation of pancreatic islets. Biomaterials 2006; 27: 5603-17
161. Antosiak-Iwanska M, Sitarek E, Sabat M, et al. Isolation, banking, encapsulation and transplantation of different types of Langerhans islets. Pol Arch Med Wewn 2009; 119: 311-7
162. Schneider S, Klein HH. Preserved insulin secretion capacity and graft function of cryostored encapsulated rat islets. Regul Pept 2011; 166: 135-8
163. Montanucci P, Pennoni I, Pescara T, et al. The functional performance of microencapsulated human pancreatic islet-derived precursor cells. Biomaterials 2011; 32: 9254-62
164. Veriter S, Aouassar N, Adnet PY, et al. The impact of hyperglycemia and the presence of encapsulated islets on oxygenation within a bioartificial pancreas in the presence of mesenchymal stem cells in a diabetic Wistar rat model. Biomaterials 2011; 32: 5945-56
165. Yadav N, Morris G, Harding SE, et al. Various non-injectable delivery systems for the treatment of diabetes mellitus. Endocr Metab Immune Disord Drug Targets 2009; 9: 1-13
166. Dufrane D, Goebbels RM, Gianello P. Alginate macroencapsulation of pig islets allows correction of streptozotocin-induced diabetes in primates up to 6 months without immunosuppression. Transplantation 2010; 90: 1054-62
167. Vaithilingam V, Quayum N, JoglekarMV, et al. Effect of alginate encapsulation on the cellular transcriptome of human islets. Biomaterials 2011; 32: 8416-25
168. Luca G, Fallarino F, Calvitti M, et al. Xenograft of microencapsulated sertoli cells reverses T1DM in NOD mice by inducing neogenesis of beta-cells. Transplantation 2010; 90: 1352-7
169. O'Sullivan ES, JohnsonAS,OmerA, et al. Rat islet cell aggregates are superior to islets for transplantation in microcapsules. Diabetologia 2010; 53: 937-45
170. Opara EC, Mirmalek-Sani SH, Khanna O, et al. Design of a bioartificial pancreas(+). J Investig Med 2010; 58: 831-7
171. Ngoc PK, Phuc PV, Nhung TH, et al. Improving the efficacy of type 1 diabetes therapy by transplantation of immunoisolated insulin-producing cells. Hum Cell 2011; 24: 86-95
172. Shao S, Gao Y, Xie B, et al. Correction of hyperglycemia in type 1 diabetic models by transplantation of encapsulated insulin-producing cells derived from mouse embryo progenitor. J Endocrinol 2011; 208: 245-55
173. Kishima H, Poyot T, Bloch J, et al. Encapsulated GDNF-producing C2C12 cells for Parkinson's disease: A pre-clinical study in chronic MPTP-treated baboons. Neurobiol Dis 2004; 16: 428-39
174. Grandoso L, Ponce S, Manuel I, et al. Long-term survival of encapsulated GDNF secreting cells implanted within the striatum of parkinsonized rats. Int J Pharm 2007; 343: 69-78
175. Shingo T, Date I, Yoshida H, et al. Neuroprotective and restorative effects of intrastriatal grafting of encapsulated GDNF-producing cells in a rat model of Parkinson's disease. J Neurosci Res 2002; 69: 946-54
176. Yasuhara T, Shingo T, Muraoka K, et al. Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease. J Neurosurg 2005; 102: 80-9
177. Yasuhara T, Shingo T, Muraoka K, et al. The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model. Brain Res 2005; 1038: 1-10
178. Yasuhara T, Shingo T, Muraoka K, et al. Neurorescue effects of VEGF on a rat model of Parkinson's disease. Brain Res 2005; 1053: 10-8
179. Yasuhara T, Shingo T, Kobayashi K, et al. Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease. Eur J Neurosci 2004; 19: 1494-504
180. Date I, Shingo T,Ohmoto T, et al. Long-termenhanced chromaffin cell survival and behavioral recovery in hemiparkinsonian rats with co-grafted polymerencapsulated human NGF-secreting cells. Exp Neurol 1997; 147: 10-7
181. Date I, Ohmoto T, Imaoka T, et al. Cografting with polymer-encapsulated human nerve growth factor-secreting cells and chromaffin cell survival and behavioral recovery in hemiparkinsonian rats. J Neurosurg 1996; 84: 1006-12
182. Sautter J, Tseng JL, Braguglia D, et al. Implants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor improve survival, growth, and function of fetal dopaminergic grafts. Exp Neurol 1998; 149: 230-6
183. Ahn YH, Bensadoun JC, Aebischer P, et al. Increased fiber outgrowth from xeno-transplanted human embryonic dopaminergic neurons with coimplants of polymer-encapsulated genetically modified cells releasing glial cell line-derived neurotrophic factor. Brain Res Bull 2005; 66: 135-42
184. Shanbhag MS, Lathia JD, Mughal MR, et al. Neural progenitor cells grown on hydrogel surfaces respond to the product of the transgene of encapsulated genetically engineered fibroblasts. Biomacromolecules. Epub 2010 Oct 13; DOI 10.1021/bm100699q
185. Garcia P, Youssef I, Utvik JK, et al. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease. J Neurosci 2010; 30: 7516-27
186. Klinge PM, Harmening K, Miller MC, et al. Encapsulated native and glucagon- like peptide-1 transfected human mesenchymal stem cells in a transgenic mouse model of Alzheimer's disease. Neurosci Lett 2011; 497: 6-10
187. Emerich DF, Skinner SJ, Borlongan CV, et al. The choroid plexus in the rise, fall and repair of the brain. Bioessays 2005; 27: 262-74
188. Borlongan CV, Skinner SJ, Geaney M, et al. Neuroprotection by encapsulated choroid plexus in a rodent model of Huntington's disease. Neuroreport 2004; 15: 2521-5
189. Emerich DF, Schneider P, Bintz B, et al. Aging reduces the neuroprotective capacity, VEGF secretion, and metabolic activity of rat choroid plexus epithelial cells. Cell Transplant 2007; 16: 697-705
190. Emerich DF, Thanos CG, Goddard M, et al. Extensive neuroprotection by choroid plexus transplants in excitotoxin lesioned monkeys. Neurobiol Dis 2006; 23: 471-80
191. Mittoux V, Joseph JM, Conde F, et al. Restoration of cognitive and motor functions by ciliary neurotrophic factor in a primate model of Huntington's disease. Hum Gene Ther 2000; 11: 1177-87
192. Tobias CA, Dhoot NO, Wheatley MA, et al. Grafting of encapsulated BDNF-producing fibroblasts into the injured spinal cord without immune suppression in adult rats. J Neurotrauma 2001; 18: 287-301
193. Tobias CA, Han SS, Shumsky JS, et al. Alginate encapsulated BDNFproducing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression. J Neurotrauma 2005; 22: 138-56
194. Barminko J, Kim JH, Otsuka S, et al. Encapsulated mesenchymal stromal cells for in vivo transplantation. Biotechnol Bioeng 2011; 108: 2747-58
195. Soon-Shiong P, Heintz RE, Merideth N, et al. Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet 1994; 343: 950-1
196. Calafiore R, Basta G, Luca G, et al. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: First two cases. Diabetes Care 2006; 29: 137-8
197. Calafiore R, Basta G, Luca G, et al. Standard technical procedures for microencapsulation of human islets for graft into nonimmunosuppressed patients with type 1 diabetes mellitus. Transplant Proc 2006; 38: 1156-7
198. Elliott RB, Escobar L, Tan PL, et al. Live encapsulated porcine islets from a type 1 diabetic patient 9.5 yr after xenotransplantation. Xenotransplantation 2007; 14: 157-61
199. Wynyard S, Garkavenko O, Elliot R. Multiplex high resolution melting assay for estimation of Porcine Endogenous Retrovirus (PERV) relative gene dosage in pigs and detection of PERV infection in xenograft recipients. J Virol Methods 2011; 175: 95-100
200. Tuch BE, Keogh GW, Williams LJ, et al. Safety and viability of microencapsulated human islets transplanted into diabetic humans. Diabetes Care 2009; 32: 1887-9
201. US National Institutes of Health. ClinicalTrials.gov [online]. Available from URL: Http://www.clinicaltrials.gov [Accessed 2012 May 23]
202. Stover NP, Bakay RA, Subramanian T, et al. Intrastriatal implantation of human retinal pigment epithelial cells attached to microcarriers in advanced Parkinson disease. Arch Neurol 2005; 62: 1833-7
203. Bloch J, Bachoud-Levi AC, Deglon N, et al. Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: Results of a phase I study. Hum Gene Ther 2004; 15: 968-75
204. Aebischer P, Schluep M, Deglon N, et al. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med 1996; 2: 696-9
205. Lohr M, Hoffmeyer A, Kroger J, et al. Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. Lancet 2001; 357: 1591-2
206. Salmons B, Lohr M, Gunzburg WH. Treatment of inoperable pancreatic carcinoma using a cell-based local chemotherapy: Results of a phase I/II clinical trial. J Gastroenterol 2003; 38 Suppl. 15: 78-84
207. Hasse C, Klock G, Schlosser A, et al. Parathyroid allotransplantation without immunosuppression. Lancet 1997; 350: 1296-7
208. Sieving PA, Caruso RC, Tao W, et al. Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Ehase I trial ofCNTFdelivered by encapsulated cell intraocular implants. Proc Natl Acad Sci U S A 2006; 103: 3896-901
209. Talcott KE, Ratnam K, Sundquist SM, et al. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Invest Ophthalmol Vis Sci 2011; 52: 2219-26
210. Templin C, Kotlarz D, Faulhaber J, et al. Ex vivo expanded hematopoietic progenitor cells improve cardiac function after myocardial infarction: Role of beta-catenin transduction and cell dose. J Mol Cell Cardiol 2008; 45: 394-403
211. Mazo M, Gavira JJ, Pelacho B, et al. Adipose-derived stem cells for myocardial infarction. J Cardiovasc Transl Res 2011; 4: 145-53
212. Choi D, Hwang KC, Lee KY, et al. Ischemic heart diseases: Current treatments and future. J Control Release 2009; 140: 194-202
213. Psaltis PJ, Zannettino AC, Worthley SG, et al. Concise review: Mesenchymal stromal cells: Eotential for cardiovascular repair. Stem Cells 2008; 26: 2201-10
214. Beeres SL, Atsma DE, van Ramshorst J, et al. Cell therapy for ischaemic heart disease. Heart 2008; 94: 1214-26
215. Sanz-Ruiz R, Fernandez-Santos E, Dominguez-Munoa M, et al. Early translation of adipose-derived cell therapy for cardiovascular disease. Cell Transplant 2009; 18: 245-54
216. Valina C, Pinkernell K, Song YH, et al. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J 2007; 28: 2667-77
217. Cai L, Johnstone BH, Cook TG, et al. IFATS collection: Human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells 2009; 27: 230-7
218. Miyahara Y, Nagaya N, Kataoka M, et al. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 2006; 12: 459-65
219. Rigol M, Solanes N, Farre J, et al. Effects of adipose tissue-derived stem cell therapy after myocardial infarction: Impact of the route of administration. J Card Fail 2010; 16: 357-66
220. Amado LC, Saliaris AP, Schuleri KH, et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 2005; 102: 11474-9
221. Kim YJ, Huh YM, Choe KO, et al. In vivo magnetic resonance imaging of injected mesenchymal stem cells in rat myocardial infarction; simultaneous cell tracking and left ventricular function measurement. Int J Cardiovasc Imaging 2009; 25 Suppl. 1: 99-109
222. Collins SD, Baffour R, Waksman R. Cell therapy in myocardial infarction. Cardiovasc Revasc Med 2007; 8: 43-51
223. Yasuda T, Weisel RD, Kiani C, et al. Quantitative analysis of survival of transplanted smooth muscle cells with real-time polymerase chain reaction. J Thorac Cardiovasc Surg 2005; 129: 904-11
224. Teng CJ, Luo J, Chiu RC, et al. Massive mechanical loss of microspheres with direct intramyocardial injection in the beating heart: Implications for cellular cardiomyoplasty. J Thorac Cardiovasc Surg 2006; 132: 628-32
225. Paul A, Ge Y, Prakash S, et al. Microencapsulated stem cells for tissue repairing: Implications in cell-based myocardial therapy. Regen Med 2009; 4: 733-45
226. Zhang H, Zhu SJ, Wang W, et al. Transplantation of microencapsulated genetically modified xenogeneic cells augments angiogenesis and improves heart function. Gene Ther 2008; 15: 40-8
227. Yu J, Du KT, Fang Q, et al. The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat. Biomaterials 2010; 31: 7012-20
228. Bai XP, Zheng HX, Fang R, et al. Fabrication of engineered heart tissue grafts from alginate/collagen barium composite microbeads. Biomed Mater 2011; 6: 045002
229. Dixit V, Darvasi R, ArthurM, et al. Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes. Hepatology 1990; 12: 1342-9
230. Wong H, Chang TM. Bioartificial liver: Implanted artificial cells microencapsulated living hepatocytes increases survival of liver failure rats. Int J Artif Organs 1986; 9: 335-6
231. Sgroi A, Mai G, Morel P, et al. Transplantation of encapsulated hepatocytes during acute liver failure improves survival without stimulating native liver regeneration. Cell Transplant. Epub 2011 Mar 7; DOI 10.3727/ 096368911X564976
232. Mai G, Nguyen TH, Morel P, et al. Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes. Xenotransplantation 2005; 12: 457-64
233. Li S, Sun Z, Lv G, et al. Microencapsulated UCB cells repair hepatic injure by intraperitoneal transplantation. Cytotherapy 2009; 11: 1032-40
234. Lv G, Zhao L, Zhang A, et al. Bioartificial liver system based on choanoid fluidized bed bioreactor improve the survival time of fulminant hepatic failure pigs. Biotechnol Bioeng 2011; 108: 2229-36
235. Liu ZC, Chang TM. Coencapsulation of hepatocytes and bone marrow stem cells: In vitro conversion of ammonia and in vivo lowering of bilirubin in hyperbilirubemia Gunn rats. Int J Artif Organs 2003; 26: 491-7
236. Chang Liu Z, Chang TM. Coencapsulation of hepatocytes and bone marrow cells: In vitro and in vivo studies. Biotechnol Annu Rev 2006; 12: 137-51
237. Shi XL, Zhang Y, Gu JY, et al. Coencapsulation of hepatocytes with bone marrow mesenchymal stem cells improves hepatocyte-specific functions. Transplantation 2009; 88: 1178-85
238. Gautier A, Carpentier B, Dufresne M, et al. Impact of alginate type and bead diameter on mass transfers and the metabolic activities of encapsulated C3A cells in bioartificial liver applications. Eur Cell Mater 2011; 21: 94-106
239. Coward SM, Legallais C, David B, et al. Alginate-encapsulated HepG2 cells in a fluidized bed bioreactor maintain function in human liver failure plasma. Artif Organs 2009; 33: 1117-26
240. Kinasiewicz A, Gautier A, Lewinska D, et al. Culture of C3A cells in alginate beads for fluidized bed bioartificial liver. Transplant Proc 2007; 39: 2911-3
241. Miranda JP, Rodrigues A, Tostoes RM, et al. Extending hepatocyte functionality for drug-testing applications using high-viscosity alginateencapsulated three-dimensional cultures in bioreactors. Tissue Eng Part C Methods 2010; 16: 1223-32
242. Murua A, Orive G, Hernandez RM, et al. Emerging technologies in the delivery of erythropoietin for therapeutics. Med Res Rev 2011; 31: 284-309
243. Orive G, De Castro M, Ponce S, et al. Long-term expression of erythropoietin from myoblasts immobilized in biocompatible and neovascularized microcapsules. Mol Ther 2005; 12: 283-9
244. Ponce S, Orive G, Hernandez RM, et al. In vivo evaluation of EPO-secreting cells immobilized in different alginate-PLL microcapsules. J Control Release 2006; 116: 28-34
245. CironeP,Bourgeois JM,AustinRC, et al.Anovel approach to tumor suppression with microencapsulated recombinant cells. Hum Gene Ther 2002; 13: 1157-66
246. Joki T, Machluf M, Atala A, et al. Continuous release of endostatin from microencapsulated engineered cells for tumor therapy. Nat Biotechnol 2001; 19: 35-9
247. Read TA, Sorensen DR, Mahesparan R, et al. Local endostatin treatment of gliomas administered by microencapsulated producer cells. Nat Biotechnol 2001; 19: 29-34
248. Teng H, Zhang Y, Wang W, et al. Inhibition of tumor growth in mice by endostatin derived from abdominal transplanted encapsulated cells. Acta Biochim Biophys Sin (Shanghai) 2007; 39: 278-84
249. Goren A, Dahan N, Goren E, et al. Encapsulated human mesenchymal stem cells: A unique hypoimmunogenic platform for long-term cellular therapy. FASEB J 2010; 24: 22-31
250. Kleinschmidt K, Klinge PM, Stopa E, et al. Alginate encapsulated human mesenchymal stem cells suppress syngeneic glioma growth in the immunocompetent rat. J Microencapsul 2011; 28: 621-7
251. Cirone P, Shen F, Chang PL. A multiprong approach to cancer gene therapy by coencapsulated cells. Cancer Gene Ther 2005; 12: 369-80
252. Dubrot J, Portero A, Orive G, et al. Delivery of immunostimulatory monoclonal antibodies by encapsulated hybridoma cells. Cancer Immunol Immunother 2010; 59: 1621-31
253. Pelegrin M, Marin M, Oates A, et al. Immunotherapy of a viral disease by in vivo production of therapeutic monoclonal antibodies. Hum Gene Ther 2000; 11: 1407-15
254. Piller Puicher E, Tomanin R, Salvalaio M, et al. Encapsulated engineered myoblasts can cure Hurler syndrome: Ereclinical experiments in the mouse model. Gene Ther 2012; 19: 355-64
255. Pettingill LN, Wise AK, Geaney MS, et al. Enhanced auditory neuron survival following cell-based BDNF treatment in the deaf guinea pig. PLoS One 2011; 6: E18733