The 3R principle: advancing clinical application of human pluripotent stem cells
Tóm tắt
The first derivation of human embryonic stem cells brought with it a clear understanding that animal models of human disease might be replaced by an unlimited supply of human cells for research, drug discovery, and drug development. With the advent of clinical trials using human pluripotent stem cell-based therapies, it is both timely and relevant to reflect on factors that will facilitate future translation of this technology. Human pluripotent cells are increasingly being used to investigate the molecular mechanisms that underpin normal and pathological human development. Their differentiated progeny are also being used to identify novel pharmaceuticals, to screen for toxic effects of known chemicals, and to investigate cell or tissue transplantation strategies. The intrinsic assumption of these research efforts is that the information gained from these studies will be more accurate, and therefore of greater relevance, than traditional investigations based on animal models of human disease and injury. This review will therefore evaluate how animals and animal-derived products are used for human pluripotent stem cell research, and will indicate how efforts to further reduce or remove animals and animal products from this research will increase the clinical translation of human pluripotent stem cell technologies through drug discovery, toxicology screening, and cell replacement therapies.
Tài liệu tham khảo
Animal and Plant Health Inspection Service: Animal Care Annual Report of Activities. 2007, Washington DC: United States Department of Agriculture
van der Jagt K, Munn S, Tørsløv J, de Bruijn J: Alternative Approaches can Reduce the Use of Test Animals under REACH Addendum to the Report: Assessment of Additional Testing needs Under REACH Effects of (Q)SARS, Risk Based Testing and Voluntary Industry Initiatives. 2004, Printed in Italy, © European Communities
Knight A: Systematic reviews of animal experiments demonstrate poor contributions toward human healthcare. Rev Recent Clin Trials. 2008, 3: 89-96. 10.2174/157488708784223844.
Wall RJ, Shani M: Are animal models as good as we think?. Theriogenology. 2008, 69: 2-9. 10.1016/j.theriogenology.2007.09.030.
Eastwood D, Findlay L, Poole S, Bird C, Wadhwa M, Moore M, Burns C, Thorpe R, Stebbings R: Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells. Br J Pharmacol. 2010, 161: 512-526. 10.1111/j.1476-5381.2010.00922.x.
Russell WMS, Burch RL: The Principles of Humane Experimental Techniques. 1959, London: Methuen
Ludwig TE, Levenstein ME, Jones JM, Berggren WT, Mitchen ER, Frane JL, Crandall LJ, Daigh CA, Conard KR, Piekarczyk MS, Llanas RA, Thomson JA: Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol. 2006, 24: 185-187. 10.1038/nbt1177.
Amit M, Shariki C, Margulets V, Itskovitz-Eldor J: Feeder layer- and serum-free culture of human embryonic stem cells. Biol Reprod. 2004, 70: 837-845.
Theunissen PT, Piersma AH: Innovative approaches in the embryonic stem cell test (EST). Front Biosci. 2012, 17: 1965-1975. 10.2741/4032.
Seiler AE, Spielmann H: The validated embryonic stem cell test to predict embryotoxicity in vitro. Nat Protoc. 2011, 6: 961-978. 10.1038/nprot.2011.348.
Sharp J, Keirstead HS: Therapeutic applications of oligodendrocyte precursors derived from human embryonic stem cells. Curr Opin Biotechnol. 2007, 18: 434-440. 10.1016/j.copbio.2007.10.006.
Schwartz SD, Hubschman JP, Heilwell G, Franco-Cardenas V, Pan CK, Ostrick RM, Mickunas E, Gay R, Klimanskaya I, Lanza R: Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. 2012, 379: 713-720. 10.1016/S0140-6736(12)60028-2.
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM: Embryonic stem cell lines derived from human blastocysts. Science. 1998, 282: 1145-1147.
Xu C, Inokuma MS, Denham J, Golds K, Kundu P, Gold JD, Carpenter MK: Feeder-free growth of undifferentiated human embryonic stem cells. Nat Biotechnol. 2001, 19: 971-974. 10.1038/nbt1001-971.
Stacey GN, Cobo F, Nieto A, Talavera P, Healy L, Concha A: The development of 'feeder' cells for the preparation of clinical grade hES cell lines: challenges and solutions. J Biotechnol. 2006, 125: 583-588. 10.1016/j.jbiotec.2006.03.011.
International Stem Cell Initiative Consortium, Akopian V, Andrews PW, Beil S, Benvenisty N, Brehm J, Christie M, Ford A, Fox V, Gokhale PJ, Healy L, Holm F, Hovatta O, Knowles BB, Ludwig TE, McKay RD, Miyazaki T, Nakatsuji N, Oh SK, Pera MF, Rossant J, Stacey GN, Suemori H: Comparison of defined culture systems for feeder cell free propagation of human embryonic stem cells. In Vitro Cell Dev Biol Anim. 2010, 46: 247-258. 10.1007/s11626-010-9297-z.
Couture LA: Scalable pluripotent stem cell culture. Nat Biotechnol. 2010, 28: 562-563. 10.1038/nbt0610-562.
Ohmine S, Dietz AB, Deeds MC, Hartjes KA, Miller DR, Thatava T, Sakuma T, Kudva YC, Ikeda Y: Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells. Stem Cell Res Ther. 2011, 2: 46-10.1186/scrt87.
O'Connor MD, Kardel MD, Eaves CJ: Functional assays for human embryonic stem cell pluripotency. Methods Mol Biol. 2011, 690: 67-80. 10.1007/978-1-60761-962-8_4.
Ungrin M, O'Connor MD, Eaves CJ, Zandstra PW: Phenotypic analysis of human embryonic stem cells. Curr Protoc Stem Cell Biol. 2007, 2: 1B.3.1-1B.3.25.
Dolgin E: Putting stem cells to the test. Nat Med. 2010, 16: 1354-1357. 10.1038/nm1210-1354.
Muller FJ, Laurent LC, Kostka D, Ulitsky I, Williams R, Lu C, Park IH, Rao MS, Shamir R, Schwartz PH, Schmidt NO, Loring JF: Regulatory networks define phenotypic classes of human stem cell lines. Nature. 2008, 455: 401-405. 10.1038/nature07213.
Sullivan GJ, Bai Y, Fletcher J, Wilmut I: Induced pluripotent stem cells: epigenetic memories and practical implications. Mol Hum Reprod. 2010, 16: 880-885. 10.1093/molehr/gaq091.
Stachelscheid H, Wulf-Goldenberg A, Eckert K, Jensen J, Edsbagge J, Bjorquist P, Rivero M, Strehl R, Jozefczuk J, Prigione A, Adjaye J, Urbaniak T, Bussmann P, Zeilinger K, Gerlach JC: Teratoma formation of human embryonic stem cells in three-dimensional perfusion culture bioreactors. J Tissue Eng Regen Med. 2012, 10.1002/term.1467.
Carr AJ, Vugler A, Lawrence J, Chen LL, Ahmado A, Chen FK, Semo M, Gias C, da Cruz L, Moore HD, Walsh J, Coffey PJ: Molecular characterization and functional analysis of phagocytosis by human embryonic stem cell-derived RPE cells using a novel human retinal assay. Mol Vis. 2009, 15: 283-295.
Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, Khaner H, Smith Y, Wiser O, Gropp M, Cohen MA, Even-Ram S, Berman-Zaken Y, Matzrafi L, Rechavi G, Banin E, Reubinoff B: Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell. 2009, 5: 396-408. 10.1016/j.stem.2009.07.002.
Das AK, Pal R: Induced pluripotent stem cells (iPSCs): the emergence of a new champion in stem cell technology-driven biomedical applications. J Tissue Eng Regen Med. 2010, 4: 413-421.
West PR, Weir AM, Smith AM, Donley EL, Cezar GG: Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics. Toxicol Appl Pharmacol. 2010, 247: 18-27. 10.1016/j.taap.2010.05.007.
Ebert AD, Svendsen CN: Human stem cells and drug screening: opportunities and challenges. Nat Rev Drug Discov. 2010, 9: 367-372. 10.1038/nrd3000.
Winkler J, Sotiriadou I, Chen S, Hescheler J, Sachinidis A: The potential of embryonic stem cells combined with -omics technologies as model systems for toxicology. Curr Med Chem. 2009, 16: 4814-4827. 10.2174/092986709789909657.
Vojnits K, Bremer S: Challenges of using pluripotent stem cells for safety assessments of substances. Toxicology. 2010, 270: 10-17. 10.1016/j.tox.2009.12.003.
Sartipy P, Bjorquist P, Strehl R, Hyllner J: The application of human embryonic stem cell technologies to drug discovery. Drug Discov Today. 2007, 12: 688-699. 10.1016/j.drudis.2007.07.005.
Murata M, Tohyama S, Fukuda K: Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery. Pharmacol Ther. 2010, 126: 109-118. 10.1016/j.pharmthera.2010.01.010.
Kola I, Landis J: Can the pharmaceutical industry reduce attrition rates?. Nat Rev Drug Discov. 2004, 3: 711-715. 10.1038/nrd1470.
Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL: How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov. 2010, 9: 203-214.
The Innovative Medicines Initiative. [http://www.imi.europa.eu/]
European Commission, Consumer Affairs. [http://ec.europa.eu/consumers/sectors/cosmetics/documents/revision/index_en.htm]
Amore BM, Gibbs JP, Emery MG: Application of in vivo animal models to characterize the pharmacokinetic and pharmacodynamic properties of drug candidates in discovery settings. Comb Chem High Throughput Screen. 2010, 13: 207-218. 10.2174/138620710790596808.
Scott L, Eskes C, Hoffmann S, Adriaens E, Alepee N, Bufo M, Clothier R, Facchini D, Faller C, Guest R, Harbell J, Hartung T, Kamp H, Varlet BL, Meloni M, McNamee P, Osborne R, Pape W, Pfannenbecker U, Prinsen M, Seaman C, Spielmann H, Stokes W, Trouba K, Berghe CV, Goethem FV, Vassallo M, Vinardell P, Zuang V: A proposed eye irritation testing strategy to reduce and replace in vivo studies using bottom-up and top-down approaches. Toxicol In Vitro. 2010, 24: 1-9. 10.1016/j.tiv.2009.05.019.
Genschow E, Spielmann H, Scholz G, Pohl I, Seiler A, Clemann N, Bremer S, Becker K: Validation of the embryonic stem cell test in the international ECVAM validation study on three in vitro embryotoxicity tests. Altern Lab Anim. 2004, 32: 209-244.
Wobus AM, Boheler KR: Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev. 2005, 85: 635-678. 10.1152/physrev.00054.2003.
Webb S: Burgeoning stem cell product market lures major suppliers. Nat Biotechnol. 2010, 28: 535-536. 10.1038/nbt0610-535.
D'Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE: Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006, 24: 1392-1401. 10.1038/nbt1259.
Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L: Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009, 27: 275-280. 10.1038/nbt.1529.
Yang C, Yang Y, Brennan L, Bouhassira EE, Kantorow M, Cvekl A: Efficient generation of lens progenitor cells and lentoid bodies from human embryonic stem cells in chemically defined conditions. FASEB J. 2010, 24: 3274-3283. 10.1096/fj.10-157255.
Sharma R, Greenhough S, Medine CN, Hay DC: Three-dimensional culture of human embryonic stem cell derived hepatic endoderm and its role in bioartificial liver construction. J Biomed Biotechnol. 2010, 2010: 236147-
Guenou H, Nissan X, Larcher F, Feteira J, Lemaitre G, Saidani M, Del Rio M, Barrault CC, Bernard FX, Peschanski M, Baldeschi C, Waksman G: Human embryonic stem-cell derivatives for full reconstruction of the pluristratified epidermis: a preclinical study. Lancet. 2009, 374: 1745-1753. 10.1016/S0140-6736(09)61496-3.
Nistor G, Seiler MJ, Yan F, Ferguson D, Keirstead HS: Three-dimensional early retinal progenitor 3D tissue constructs derived from human embryonic stem cells. J Neurosci Methods. 2010, 190: 63-70. 10.1016/j.jneumeth.2010.04.025.
Zweigerdt R: The art of cobbling a running pump-will human embryonic stem cells mend broken hearts?. Semin Cell Dev Biol. 2007, 18: 794-804. 10.1016/j.semcdb.2007.09.014.
Katsnelson A: Making lungs in the lab. [http://www.nature.com/news/2010/100624/full/news.2010.314.html]
O'Connor MD, McAvoy JW: In vitro generation of functional lens-like structures with relevance to age-related nuclear cataract. Invest Ophthalmol Vis Sci. 2007, 48: 1245-1252. 10.1167/iovs.06-0949.
O'Connor MD, Wederell ED, de Iongh R, Lovicu FJ, McAvoy JW: Generation of transparency and cellular organization in lens explants. Exp Eye Res. 2008, 86: 734-745. 10.1016/j.exer.2008.01.020.
Sharp J, Frame J, Siegenthaler M, Nistor G, Keirstead HS: Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants improve recovery after cervical spinal cord injury. Stem Cells. 2010, 28: 152-163.
Lu M, Kardel MD, O'Connor MD, Eaves CJ: Enhanced generation of hematopoietic cells from human hepatocarcinoma cell-stimulated human embryonic and induced pluripotent stem cells. Exp Hematol. 2009, 37: 924-936. 10.1016/j.exphem.2009.05.007.
Carr AJ, Vugler AA, Hikita ST, Lawrence JM, Gias C, Chen LL, Buchholz DE, Ahmado A, Semo M, Smart MJ, Hasan S, da Cruz L, Johnson LV, Clegg DO, Coffey PJ: Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One. 2009, 4: e8152-10.1371/journal.pone.0008152.
Martin MJ, Muotri A, Gage F, Varki A: Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med. 2005, 11: 228-232. 10.1038/nm1181.
Cerdan C, Bendall SC, Wang L, Stewart M, Werbowetski T, Bhatia M: Complement targeting of nonhuman sialic acid does not mediate cell death of human embryonic stem cells. Nat Med. 2006, 12: 1113-1114. 10.1038/nm1006-1113. author reply 1115
Okamura RM, Lebkowski J, Au M, Priest CA, Denham J, Majumdar AS: Immunological properties of human embryonic stem cell-derived oligodendrocyte progenitor cells. J Neuroimmunol. 2007, 192: 134-144. 10.1016/j.jneuroim.2007.09.030.
Nasonkin IO, Koliatsos VE: Nonhuman sialic acid Neu5Gc is very low in human embryonic stem cell-derived neural precursors differentiated with B27/N2 and noggin: implications for transplantation. Exp Neurol. 2006, 201: 525-529. 10.1016/j.expneurol.2006.05.002.
Baylis F: Geron's discontinued stem cell trial: what about the research participants?. Bioethics Forum. 2011, [http://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=5640&blogid=140]