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Cell Models for drug discovery and pre-clinical research

  1. Mata S, Franchi-Mendes T, Abreu S, Filipe B, Morgado S, Mesquita M, Albuquerque C, Fonseca R, Santo VE, Boghaert ER, Rosa I, Brito C. 2021. Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures. MDPI Cancers. 13 (18): 4695. doi: 10.3390/cancers13184695

  2. Franchi‐Mendes T, Eduardo R, Domenici G, Brito C. 2021. 3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment. MDPI Cancers. 13: 4610. doi: 10.3390/cancers13184610

  3. Cox MC, Mendes R, Silva F, Mendes TF, Zelaya-Lazo A, Halwachs K, Purkal JJ, Isidro IA, Félix A, Boghaert ER, Brito C. 2021. Application of LDH assay for therapeutic efficacy evaluation of ex vivo tumor models. Scientific Reports. 11: 18571. doi: 10.1038/s41598-021-97894-0

  4. Franchi-Mendes T, Lopes N, Brito C. 2021. Heterotypic tumor spheroids in agitation-based cultures: a scaffold-free cell model that sustains long-term survival of endothelial cells. Frontiers in Bioengineering and Biotechnology. doi: 10.3389/fbioe.2021.649949

  5. Arez F, Rodrigues AF, Brito C, Alves PM. 2021. Bioengineered Liver Cell Models of Hepatotropic Infections. Viruses. 13(5): 773. doi:10.3390/v13050773

  6. Batalha S, Ferreira S, Brito C. 2021. The Peripheral Immune Landscape of Breast Cancer: Clinical Findings and In Vitro Models for Biomarker Discovery. Cancers. 13(6): 1305. doi:10.3390/cancers13061305

  7. Isidro IA, Vicente P, Pais DAM, Almeida JI, Domingues M, Abecasis B, Zapata-Linares N, Rodriguez-Madoz JR, Prosper F, Aspegren A, Alves PM, Serra M. 2021. Online monitoring of hiPSC expansion and hepatic differentiation in 3D culture by dielectric spectroscopy. Biotechnology & Bioengineering. doi:10.1002/bit.27751

  8. Domenici G, Eduardo R, Castillo-Ecija H, Orive G, Carcaboso AM, Brito C. 2021. PDX-Derived Ewing’s Sarcoma Cells Retain High Viability and Disease Phenotype in Alginate Encapsulated Spheroid Cultures. Cancers. 13(4): 879. doi:10.3390/cancers13040879

  9. Lopes N, Correia VG, Palma AS, Brito C. 2021. Cracking the Breast Cancer Glyco-Code through Glycan-Lectin Interactions: Targeting Immunosuppressive Macrophages. International Journal of Molecular Sciences. 22(4): 1972. doi:10.3390/ijms22041972

  10. Abreu S, Silva F, Mendes R, Mendes TF, Teixeira M, Santo VE, Boghaert E, Félix A, Brito C. Patient-derived ovarian cancer explants: preserved viability and histopathological features in long-term agitation-based cultures. Scientific Reports. 2020. 10:19462. doi: 10.1038/s41598-020-76291-z

  11. Cartaxo AL, Almeida J, Gualda EJ, Marsal M, Loza-Alvarez P, Brito C, Isidro IA. 2020. A computational diffusion model to study antibody transport within reconstructed tumor microenvironments. BMC Bioinformatics. 21:529. doi: 10.1186/s12859-020-03854-2​

  12. Cartaxo AS, Estrada MF, Domenici G, Roque R, Silva F, Gualda EJ, Loza-Alvarez P, Sflomos G, Brisken C, Alves PM, André S, Brito C. 2020. A novel culture method that sustains ERα signaling in human breast cancer tissue microstructures. Journal of Experimental & Clinical Cancer Research. 39:161. doi:10.1186/s13046-020-01653-4

  13. Lopes-Coelho F, Silva F, Gouveia-Fernandes S, Martins C, Lopes N, Domingues G, Brito C, Almeida AM, Pereira SA, Serpa J. 2020. Monocytes as endothelial percursor cells (EPCs), another brick in the wall to disentangle tumor angiogenesis. Cells. 9(1): 107. doi:10.3390/cells9010107

  14. Raposo CD, Costa R, Petrova KT, Brito C, Scotti MT, Cardoso MM. 2020. Development of Novel Galactosylated PLGA Nanoparticles for Hepatocyte Targeting Using Molecular Modelling. Polymers. 12(1): 94. doi:10.3390/polym12010094

  15. Sebastião MJ, Gomes-Alves P, Reis I, Sanchez B, Palacios I, Serra M, Alves PM. 2019. Bioreactor-based 3D human myocardial ischemia/reperfusion in vitro model: a novel tool to unveil key paracrine factors upon AMI. Translational Research. doi: 10.1016/j.trsl.2019.09.001

  16. Arez F, Rebelo SP, Fontinha D, Simão D, Martins TR, Machado M, Fischli C, Oeuvray C, Badolo L, Carrondo MJT, Rottmann M, Spangenberg T, Brito C, Greco B, Prudêncio M, Alves PM. 2019. Flexible 3D Cell-Based Platforms for the Discovery and Profiling of Novel Drugs Targeting Plasmodium Hepatic Infection. ACS Infectious Diseases. doi: 10.1021/acsinfecdis.9b00144

  17. Torán JL, López JA, Gomes-Alves P, Aguilar S, Torroja C, Trevisan-Herraz M, Moscoso I, Sebastião MJ, Serra M, Brito C, Cruz FM, Sepúlveda JC, Abad JL, Galán-Arriola C, Ibanez B, Martínez F, Fernández ME, Fernández-Aviles F, Palacios I, R-Borlado L, Vázquez J, Alves PM, Bernad A. 2019. Definition of a cell surface signature for human cardiac progenitor cells after comprehensive comparative transcriptomic and proteomic characterization. Sci Rep.  Mar 15;9(1):4647. https://doi.org/10.1038/s41598-019-39571-x

  18. Sebastião MJ, Serra M, Pereira R, Palacios I, Gomes-Alves P, Alves PM. 2019. Human cardiac progenitor cell activation and regeneration mechanisms: exploring a novel myocardial ischemia/reperfusion in vitro model. Stem Cell Res Ther. Mar 7;10(1):77. https://doi.org/10.1186/s13287-019-1174-4

  19. Sebastião MJ, Pereira R, Serra M, Gomes-Alves P, Alves PM. 2018. Unveiling Human Cardiac Fibroblast Membrane Proteome. Proteomics. 18(13):e1700446. https://doi.org/10.1002/pmic.201700446.

  20. Rebelo SP, Pinto C, Martins TR, et al. 2018. 3D-3-culture: A tool to unveil macrophage plasticity in the tumour microenvironment. Biomaterials. 163:185-197. https://doi.org/10.1016/j.biomaterials.2018.02.030.

  21. Simão D, Silva MM, Terrasso AP, et al. 2018. Recapitulation of Human Neural Microenvironment Signatures in iPSC-Derived NPC 3D Differentiation. Stem cell reports. 11(2):552-564. https://doi.org/10.1016/j.stemcr.2018.06.020.

  22. Nunes SC, Ramos C, Lopes-Coelho F, et al. 2018. Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity. Sci Rep. 8(1). https://doi.org/10.1038/s41598-018-27753-y.

  23. Coelho R, Marcos-Silva L, Mendes N, et al. 2018. Mucins and Truncated O-Glycans Unveil Phenotypic Discrepancies between Serous Ovarian Cancer Cell Lines and Primary Tumours. Int J Mol Sci. 19(7):E2045. https://doi.org/10.3390/ijms19072045

  24. Hu D, Linders A, Yamak A, et al. 2018. Metabolic Maturation of Human Pluripotent Stem Cell Derived Cardiomyocytes by Inhibition of HIF1α and LDHA Basic Science Research Cell Signaling/Signal Transduction Contractile Function Metabolism Stem Cells. 1066-1079. https://doi.org/10.1161/CIRCRESAHA.118.313249

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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 

  34. 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 

  35. 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

  36. 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 

  37. 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] 

  38. 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

  39. 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 

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

  48. 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

  49. 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

  50. 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

  51. 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

  52. 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

  53. 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

  54. 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

  55. 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

  56. 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

  57. 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

  58. 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

  59. 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

  60. 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

  61. 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

  62. 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

  63. 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

  64. 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

  65. 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

  66. 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

  67. 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

  68. 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

  69. 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

  70. 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

  71. 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

  72. 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

  73. 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

  74. 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

  75. 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

  76. 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

  77. 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

  78. 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

  79. 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

  80. 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

  81. 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

  82. 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

  83. 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

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