Personal tools
You are here: Home / Labs / Animal Cell Technology Unit / Publications / Papers by topic (peer-review) / In vitro models for pre-clinical research

In vitro models for pre-clinical research

  1. Abecasis B, Aguiar T, Arnault E, Costa R, Gomes-Alves P, Aspegren A, Serra M, Alves PM. 2017.  Expansion of 3D human induced pluripotent stem cell aggregates in bioreactors: Bioprocess intensification and scaling-up approaches.  J Biotechnol. 246:81-93. http://dx.doi.org/10.1016/j.jbiotec.2017.01.004
  2. Stock K, Estrada MF, Vidic S, Gjerde K, Rudisch A, Santo VE, Barbier M, Blom S, Arundkar SC, Selvam I, Osswald A, Stein Y, Gruenewald S, Brito C, van Weerden W, Rotter V, Boghaert E, Oren M, Sommergruber W, Chong Y, de Hoogt R, Graeser R. 2016. Capturing tumor complexity in vitro: Comparative analysis of 2D and 3D tumor models for drug discovery. Scientific Reports. 6, 28951.  http://dx.doi.org/10.1038/srep28951
  3. Santo VE, Rebelo SP, Estrada MF, Alves PM, Boghaert E, Brito C. 2016. Drug screening in 3D in vitro tumor models: overcoming current pitfalls of efficacy read-outs. Biotechnology Journal.  https://doi.org/10.1002/biot.201600505
  4. Barbier M, Jaensch S, Cornelissen F, Vidic S, Gjerde K, de Hoogt R, Graeser R, Gustin E, Chong YT; Hickman J, Burbridge M, Verschuren E, Kallioniemi O, Klefström J, Brisken C, Rotter V, Oren M, Brito C, Schalken J, Jenster G, van Weerden W, Vilo J, Schueler J, Monni O, Barry ST, Grünewald S, Kallio P, Mueller H, Nopora A, Sommergruber W, Anderson E, van der Kuip H, Smalley M,  Boghaert E. .  2016.  Ellipsoid Segmentation Model for Analyzing Light-Attenuated 3D Confocal Image Stacks of Fluorescent Multi-Cellular Spheroids.  PLoS One .  11, e0156942. http://dx.doi.org/10.1371/journal.pone.0156942
  5. Terrasso AP, Silva AC, Filipe A, Pedroso P, Ferreira AL, Alves PM, Brito C.  2016.  Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds.  J Pharmacol Toxicol Methods.  83:72-79. https://doi.org/10.1016/j.vascn
  6. Simão D, Terrasso AP, Teixeira AP, Brito C, Sonnewald U, Alves PM .  2016.  Functional metabolic interactions of human neuron-astrocyte 3D in vitro networks.  Scientific Reports. 6, 33285. http://dx.doi.org/10.1038/srep33285
  7. Santo VE, Estrada MF, Rebelo SP, Abreu S, Silva I, Pinto C, Veloso SC, Serra AT, Boghaert E, Alves PM, Brito, C. 2016. Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models. J Biotechnol. 221 118-29. http://dx.doi.org/10.1016/j.jbiotec.2016.01.031
  8. Estrada MF, Rebelo SP, Davies EJ, Pinto MT, Pereira H, Santo VE, Smalley MJ, Barry ST, Gualda EJ, Alves PM, Anderson E, Brito C. 2016. Modelling the tumour microenvironment in long-term microencapsulated 3D co-cultures recapitulates phenotypic features of disease progression. Biomaterials. 78:50-61. http://dx.doi.org/10.1016/j.biomaterials.2015.11.030
  9. Rebelo SP, Costa R, Silva MM, Marcelino P, Brito C, Alves PM. 2015. Three-dimensional co-culture of human hepatocytes and mesenchymal stem cells: improved functionality in long-term bioreactor cultures. J Tissue Eng Regen Med. http://dx.doi.org/10.1002/term.2099 
  10. Piersanti S, Burla R, Licursi V, Brito C, La Torre M, Alves PM, Simao D, Mottini C, Salinas S, Negri R, Tagliafico E, Kremer EJ, Saggio I. 2015. Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups. PLoS One. 10(7):e0133607. http://dx.doi.org/10.1371/journal.pone.0133607 
  11. Simão D, Pinto C, Fernandes P, Peddie CJ, Piersanti S, Collinson LM, Salinas S, Saggio I, Schiavo G, Kremer EJ, Brito C, Alves PM. 2016. Evaluation of helper-dependent canine adenovirus vectors in a 3D human CNS model. Gene Ther. http://dx.doi.org/10.1038/gt.2015.75
  12. Materne EM, Ramme AP, Terrasso AP, Serra M, Alves PM, Brito C, Sakharov DA, Tonevitsky AG, Lauster R, Marx U. 2015. A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing. J Biotechnol. Feb 9. pii: S0168-1656(15)00045-0. http://dx.doi.org/10.1016/j.jbiotec.2015.02.002 
  13. Suter-Dick L, Alves PM, Blaauboer BJ, Bremm KD, Brito C, Coecke S, Flick B, Fowler P, Hescheler J, Ingelman-Sundberg M, Jennings P, Kelm JM, Manou I, Mistry P, Moretto A, Roth A, Stedman D, van de Water B, Beilmann M. 2015. Stem Cell-Derived Systems in Toxicology Assessment. Stem Cells Dev. Mar 31. [Epub ahead of print] 
  14. Terrasso AP, Pinto C, Serra M, Filipe A, Almeida S, Ferreira AL, Pedroso P, Brito C, Alves PM. Novel scalable 3D cell based model for in vitro neurotoxicity testing: Combining human differentiated neurospheres with gene expression and functional endpoints. J Biotechnol. 2015 Jan 5. pii: S0168-1656(14)01047-5. http://dx.doi.org/10.1016/j.jbiotec.2014.12.011
  15. Simão D, Pinto C, Piersanti S, Weston A, Peddie CJ, Bastos AE, Licursi V, Schwarz SC, Collinson LM, Salinas S, Serra M, Teixeira AP, Saggio I, Lima PA, Kremer EJ, Schiavo G, Brito C, Alves PM. 2015. Modeling human neural functionality in vitro: three-dimensional culture for dopaminergic differentiation. Tissue Eng Part A. 2015 Feb;21(3-4):654-68. http://dx.doi.org/10.1089/ten.TEA.2014.0079 
  16. Gualda EJ, Simão D, Pinto C, Alves PM, Brito C. 2014. Imaging of human differentiated 3D neural aggregates using light sheet fluorescence. Frontiers in Cellular Neuroscience, 8:221. http://dx.doi.org/10.3389/fncel.2014.00221
  17. Rebelo SP, Costa R, Estrada M, Shevchenko V, Brito C, Alves PM. 2014. HepaRG microencapsulated spheroids in DMSO‑free culture: novel culturing approaches for enhanced xenobiotic and biosynthetic metabolism. Archives of Toxicology. Published on line 09 August 2014. http://dx.doi.org/10.1007/s00204-014-1320-9
  18. Correia C, Serra M, Espinha N, Sousa M, Brito C, Burkert K, Zheng Y, Hescheler J, Carrondo MJ, Sarić T, Alves PM. 2014. Combining Hypoxia and Bioreactor Hydrodynamics Boosts Induced Pluripotent Stem Cell Differentiation Towards Cardiomyocytes. Stem Cell Reviews and Reports. Published on line 15 July 2014. http://dx.doi.org/10.1007/s12015-014-9533-0
  19. Hickman J, Graeser R, De Hoogt R, Vidic S, Brito C, Gutekunst M, Van der Kuip H. 2014. Capturing tumor complexity in vitro/ex vivo: three dimensional models of cancer for pharmacology and cancer cell biology. Biotechnology Journal. Biotechnology Journal, 9: 1115-28. http://dx.doi.org/10.1002/biot.201300492
  20. Tostões R, Leite SB, Serra M, Jensen J, Björquist P, Carrondo MJ, Brito C, Alves PM, 2012. Human liver cell spheroids in extended perfusion bioreactor culture for repeated dose drug testing. Hepatology, 55(4): 1227-36. http://dx.doi.org/10.1002/hep.24760
  21. Serra M, Brito C, Correia C, Alves PM, 2012. Process engineering of human pluripotent stem cells for clinical applications. Trends Biotechnol, 30(6):350-9. http://dx.doi.org/10.1016/j.tibtech.2012.03.003
  22. Almeida AS, Queiroga CS, Sousa MF, Alves PM, Vieira HL, 2012. Carbon monoxide modulates apoptosis by reinforcing oxidative metabolism in astrocytes: role of BCL-2. J Biol Chem, 287 (14): 10761-70. http://dx.doi.org/10.1074/jbc.M111.306738
  23. Brito C, Simão D, Costa I, Malpique R, Pereira CI, Fernandes P, Serra M, Schwarz SC, Schwarz J, Kremer EJ, Alves PM, 2012. Generation and genetic modification of 3D cultures of human dopaminergic neurons derived from neural progenitor cells. Methods, 56(3):452-60. http://dx.doi.org/10.1016/j.ymeth.2012.03.005
  24. Leite SB, Wilk-Zasadna I, Zaldivar Comenges JM, Airola E, Reis-Fernandes MA, Mennecozzi M, Guguen-Guillouzo C, Chesne C, Gouillou C, Alves PM, Coecke S, 2012. 3D HepaRG model as an attractive tool for toxicity testing. Toxicol Sci 130 (1): 106-116. http://dx.doi.org/10.1093/toxsci/kfs232
  25. Queiroga CS, Tomasi S, Wideroe M, Alves PM, Vercelli A, Vieira HL, 2012. Preconditioning triggered by Carbon Monoxide (CO) provides neuronal protection following perinatal hypoxia-ischemia. Plos One, 7(8): e42632. http://dx.doi.org/10.1371/journal.pone.0042632
  26. Lamego J, Cunha B, Peixoto C, Sousa MF, Alves PM, Simplicio AL, Coroadinha AS, 2012. Carboxylesterase 2 production and characterization in human cells: new insights into enzyme oligomerization and activity. Appl Microbiol Biotechnol, 97 (3): 1161-73. http://dx.doi.org/10.1007/s00253-012-3994-3
  27. Malpique R, Tostões R, Beier AF, Serra M, Brito C, Schulz JC, Björquist P, Zimmermann H, Alves PM, 2012. Surface-based cryopreservation strategies for human embryonic stem cells: A comparative study. Biotechnol Prog, 28(4):1079-87. http://dx.doi.org/10.1002/btpr.1572
  28. Tavares L, Figueira I, McDougall GJ, Vieira HL, Stewart D, Alves PM, Ferreira RB, Santos CN, 2012. Neuroprotective effects of digested polyphenols from wild blackberry species. Eur J Nutr. http://dx.doi.org/10.1007/s00394-012-0307-7
  29. Queiroga CS, Almeida AS and Vieira HL, 2012. Carbon monoxide targeting mitochondria. Biochem Res Int, 2012:749845. http://dx.doi.org/10.1155/2012/749845
  30. Vieira HL, Alves PM, Vercelli A, 2011. Modulation of neuronal stem cell differentiation by hypoxia and reactive oxygen species. Prog Neurobiol, 93:444-55. http://dx.doi.org/10.1016/j.pneurobio.2011.01.007
  31. Serra M, Correia C, Malpique R, Brito C, Jensen J, Bjorquist P, Carrondo MJ, Alves PM, 2011. Microencapsulation technology: a powerful tool for integrating expansion and cryopreservation of human embryonic stem cells. Plos One, 6(8) e23212. http://dx.doi.org/10.1371/journal.pone.0023212
  32. Tostões RM, Leite SB, Miranda JP, Sousa MF, Wang DIC, Carrondo MJ, Alves PM, 2011. Perfusion of 3D encapsulated hepatocytes-a synergistic effect enhancing long-term functionality in bioreactors. Biotechnol Bioeng, 108: 41-49. http://dx.doi.org/10.1002/bit.22920
  33. Santos SS, Sonnewald U, Carrondo MJ, Alves PM, 2011. The role of glia in neuronal recovery following anoxia: in vitro evidence of neuronal adaptation. Neurochem Int, 58:665-75. http://dx.doi.org/10.1016/j.neuint.2011.02.005
  34. Leite SB, Teixeira AP, Miranda JP, Tostoes RM, Clemente JJ, Sousa MF, Carrondo MJ, Alves PM, 2011. Merging bioreactor technology with 3D hepatocyte-fibroblast culturing approaches: improved in vitro models for Toxicological applications. Toxicol in Vitro, 25(4):825-32. http://dx.doi.org/10.1016/j.tiv.2011.02.002
  35. Queiroga CS, Almeida AS, Alves PM, Brenner C, Vieira HL, 2011. Carbon monoxide prevents hepatic mitochondrial membrane permeabilization. BMC Cell Biol 12:10. http://dx.doi.org/10.1186/1471-2121-12-10
  36. Amaral AI , Teixeira AP, Sonnewald U, Alves PM, 2011. Estimation of intracellular fluxes in cerebellar neurons after hypoglyce: importance of the pyruvate recycling pathway and glutamine oxidation. J Neurosci Res, 89(5)-700:10. http://dx.doi.org/10.1002/jnr.22571
  37. Amaral IA, Teixeira AP, Håkonsen BI, Sonnewald U, Alves PM, 2011. A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and 13C-labelled glucose. Front Neuroenerg, 3:5. http://dx.doi.org/10.3389/fnene.2011.00005
  38. Adler S, Basketter D, Creton S, Pelkonen O, van Benthem J, Zuang V, Andersen KE, Angers-Loustau A, Aptula A, Bal-Price A, Benfenati E, Bernauer U, Bessems J, Bois FY, Boobis A, Brandon E, Bremer S, Broschard T, Casati S, Coecke S, Corvi R, Cronin M, Daston G, Dekant W, Felter S, Grignard E, Gundert-Remy U, Heinonen T, Kimber I, Kleinjans J, Komulainen H, Kreiling R, Kreysa J, Mazzatorta P, Maxwell G, Munn S, Leite SB, Loizou G, Pfuhler S, Phrakonkham P, Piersma A, Poth A, Prieto P, Repetto G, Rogiers V, Schoeters G, Schwarz M, Serafimova R, Tähti H, Testai E, van Delft J, van Loveren H, Vinken M, Worth A, Zaldivar JM, 2011. Alternative (non-animal) methods for cosmetics testing: current status and future prospects. Arch Toxicol, 85(5):367-485. http://dx.doi.org/10.1007/s00204-011-0693-2
  39. Amaral AI, Teixeira AP, Martens S, Sousa MF, Bernal V, Alves PM, 2010. Metabolic alterations induced by ischemia in primary cultures of astrocytes: merging 13C NMR spectroscopy and metabolic flux analysis. J Neurochem, 113(3):735-48. http://dx.doi.org/10.1111/j.1471-4159.2010.06636.x
  40. Miranda JP, Rodrigues A, Tostões RM, Leite SB, Zimmerman H, Carrondo MJ, Alves PM, 2010. Extending hepatocyte functionality for drug-testing applications using high-viscosity alginate-encapsulated three-dimensional cultures in bioreactors. Tissue Eng Part C Methods, 16(6):1223-32. http://dx.doi.org/10.1089/ten.tec.2009.0784
  41. Malpique R, Osório LM, Ferreira DS, Ehrhart F, Brito C, Zimmermann H, Alves PM, 2010. Alginate encapsulation as a novel strategy for the cryopreservation of neurospheres. Tissue Eng Part C Methods, 16(5):965-77. http://dx.doi.org/10.1089/ten.tec.2009.0660
  42. Serra M, Brito C, Sousa MF, Jensen J, Tostões RM, Clemente JJ, Hyllner J, Strehl R, Carrondo MJ, Alves PM, 2010. Improving expansion of pluripotent human embryonic stem cells in perfused bioreactors through oxygen control. J Biotechnol, 148(4):208-15. http://dx.doi.org/10.1016/j.jbiotec.2010.06.015
  43. Fortalezas S, Tavares L, Pimpão R, Tyagi M, Pontes V, Alves PM, McDougall G, Stewart D, Ferreira RB, Santos CN, 2010. Antioxidant properties and neuroprotective capacity of strawberry tree fruit (Arbutus unedo). Nutrients, 2(2):214-29. http://dx.doi.org/10.3390/nu2020214
  44. Miranda JP, Leite SB, Muller-Vieira U, Rodrigues A, Carrondo MJ, Alves PM, 2009. Toward extended functional hepatocyte in vitro culture. Tissue Eng Part C Methods, 15:1-11. http://dx.doi.org/10.1089/ten.tec.2008.0352
  45. Malpique R, Ehrhart F, Katsen-Globa A, Zimmermann H, Alves PM, 2009. Cryopreservation of adherent cells: strategies to improve cell viability and function after thawing. Tissue Eng Part C Methods, 15(3):373-86. http://dx.doi.org/10.1089/ten.tec.2008.0410
  46. Serra M, Brito C, Costa E, Sousa MF, Alves PM, 2009. Integrating human stem cell expansion and neuronal differentiation in bioreactors. BMC Biotechnol, 9:82. http://dx.doi.org/10.1186/1472-6750-9-82
  47. Serra M, Brito C, Leite SB, Gorjup E, von Briesen H, Carrondo MJ, Alves PM, 2009. Stirred bioreactors for the expansion of adult pancreatic stem cells. Ann Anat, 191:104-15. http://dx.doi.org/10.1016/j.aanat.2008.09.005
  48. Güll I, Alves PM, Gabor F, Wirth M, 2009. Viability of human adenocarcinoma cell line Caco-2: influence of cryoprotectant, freezing rate, and storage temperature. Sci Pharm, 77:133-41. http://dx.doi.org/10.3797/scipharm.0810-07
  49. Vieira HL, Queiroga CS, Alves PM, 2008. Preconditioning induced by Carbon Monoxide provides neuronal protection against apoptosis. J Neurochem, 107:375-84. http://dx.doi.org/10.1111/j.1471-4159.2008.05610.x
  50. Teixeira AP, Santos SS, Carinhas N, Oliveira R, Alves PM, 2008. Combining metabolic flux analysis tools and 13C-NMR to estimate intracellular fluxes of cultured astrocytes. Neurochem Int, 52:478-86. http://dx.doi.org/10.1016/j.neuint.2007.08.007
  51. Petrovski Z, Norton de Matos MR, Braga SS, Pereira CC, Matos ML, Gonçalves IS, Pillinger M, Alves PM, Romão CC, 2008. Synthesis, characterization and antitumor activity of 1,2-disubstituted ferrocenes and cyclodextrin inclusion complexes. J Organomet Chem, 693:675-84. http://dx.doi.org/10.1016/j.jorganchem.2007.11.053
  52. Malpique R, Katsen-Globa A, Carrondo MJ, Zimmermann H, Alves PM, 2007. Cryopreservation in micro-volumes: impact upon Caco-2 colon adenocarcinoma cells proliferation and differentiation. Biotechnol Bioeng, 98:155-66. http://dx.doi.org/10.1002/bit.21382
  53. Santos SS, Leite SB, Sonnewald U, Carrondo MJ, Alves PM, 2007. Stirrer vessel cultures of rat brain cells aggregates: characterization of major metabolic pathways and cell population dynamics. J Neurosci Res, 85(15):3386-97. http://dx.doi.org/10.1002/jnr.21409
  54. Serra M, Leite SB, Brito C, Costa J, Carrondo MJ, Alves PM, 2007. Novel culture strategy for human stem cell proliferation and neuronal differentiation. J Neurosci Res, 85(16):3557-66. http://dx.doi.org/10.1002/jnr.21451
  55. Santos SS, Gibson GE, Cooper AJ, Denton TT, Thompson CM, Bunik VI, Alves PM, Sonnewald U, 2006. Inhibitors of the a-ketoglutarate dehydrogenase complex alter [1-13C]Glucose and [U-13C]Glutamate metabolism in cerebellar granule neurons. J Neurosci Res, 83:450-8. http://dx.doi.org/10.1002/jnr.20749
  56. Fonseca LL, Monteiro MA, Alves PM, Carrondo MJ, Santos H, 2005. Cultures of rat astrocytes challenged with a steady supply of glutamate: a new model to study flux distribution in the glutamate-glutamine cycle. Glia, 51:286-96. http://dx.doi.org/10.1002/glia.20209
  57. Santos SS, Fonseca LL, Monteiro MA, Carrondo MJ, Alves PM,  2005. Culturing primary brain astrocytes under fully controlled environment in a novel bioreactor. J Neurosci Res, 79:26-32. http://dx.doi.org/10.1002/jnr.20279
  58. Alves PM, Fonseca LL, Peixoto CC, Almeida AC, Carrondo MJ, Santos H, 2000. NMR studies on energy metabolism of immobilized primary neurons and astrocytes during hypoxia, ischemia and hypoglycemia. NMR Biomed, 13:438-48. http://dx.doi.org/10.1002/nbm.665
  59. Alves PM, Nunes R, Zhang C, Maycock CD, Sonnewald U, Carrondo MJ, Santos H, 2000. Metabolism of 3-[13C]malate in primary cultures of mouse astrocytes. Dev Neurosci, 22:456-62. http://dx.doi.org/10.1159/000017475
  60. Alves PM, JL Moreira, JM Rodrigues, JG Aunins, MJ Carrondo, 1996. Two-dimensional versus three-dimensional culture systems: effects on growth and productivity of BHK cells. Biotechnol Bioeng, 52:429-32. http://dx.doi.org/10.1002/(SICI)1097-0290(19961105)52:3<429::AID-BIT9>3.0.CO;2-M
  61. Alves PM, Moreira JL, Rodrigues JM, Aunins JG, Carrondo MJ, 1996. Immobilization of primary astrocytes and neurons for on-line monitoring of biochemical processes by NMR. Dev Neurosci, 18:478-83. http://dx.doi.org/10.1159/000111443
  62. Alves PM, MC Mckenna, U Sonnewald, 1995. Lactate metabolism in mouse brain astrocytes studied by [13C]NMR spectroscopy. NeuroReport, 6:2201-04. http://www.ncbi.nlm.nih.gov/pubmed/8595202
  63. Moreira JL, Cruz PE, Santana P, Aunins JG, Carrondo MJ, 1995. Formation and disruption of animal cell aggregates in stirred vessels: mechanisms and kinetic studies. Chem Eng Sci, 50:2747-64. http://dx.doi.org/10.1016/0009-2509(95)00118-O
  64. Moreira JL, Alves PM, Aunins JG, Carrondo MJ, 1994. Changes in animal cell natural aggregates in suspended batch cultures. Appl Microbiol Biotechnol, 41: 203-9. http://dx.doi.org/10.1007/BF00186960
  65. Moreira JL, Alves PM, Rodrigues JM, Cruz PE, Aunins JG, Carrondo MJ, 1994. Studies of baby hamster kidney natural cell aggregation in suspended batch cultures. Ann N Y Acad Sci, 745:122-33. http://dx.doi.org/10.1111/j.1749-6632.1994.tb44368.x
  66. Moreira JL, Feliciano AS, Santana PC, Cruz PE, Aunins JG, Carrondo MJ, 1994. Repeated-batch cultures of baby hamster kidney cell aggregates in stirred vessels. Cytotechnology, 15:337-49. http://dx.doi.org/10.1007/BF00762409
Document Actions