Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Review Article

Future Perspective of Diabetic Animal Models

Author(s): Shashank Pandey and Magdalena C. Dvorakova*

Volume 20, Issue 1, 2020

Page: [25 - 38] Pages: 14

DOI: 10.2174/1871530319666190626143832

open access plus

Abstract

Objective: The need of today’s research is to develop successful and reliable diabetic animal models for understanding the disease susceptibility and pathogenesis. Enormous success of animal models had already been acclaimed for identifying key genetic and environmental factors like Idd loci and effects of microorganisms including the gut microbiota. Furthermore, animal models had also helped in identifying many therapeutic targets and strategies for immune-intervention. In spite of a quite success, we have acknowledged that many of the discovered immunotherapies are working on animals and did not have a significant impact on human. Number of animal models were developed in the past to accelerate drug discovery pipeline. However, due to poor initial screening and assessment on inequivalent animal models, the percentage of drug candidates who succeeded during clinical trials was very low. Therefore, it is essential to bridge this gap between pre-clinical research and clinical trial by validating the existing animal models for consistency.

Results and Conclusion: In this review, we have discussed and evaluated the significance of animal models on behalf of published data on PUBMED. Amongst the most popular diabetic animal models, we have selected six animal models (e.g. BioBreeding rat, “LEW IDDM rat”, “Nonobese Diabetic (NOD) mouse”, “STZ RAT”, “LEPR Mouse” and “Zucker Diabetic Fatty (ZDF) rat” and ranked them as per their published literature on PUBMED. Moreover, the vision and brief imagination for developing an advanced and robust diabetic model of 21st century was discussed with the theme of one miceone human concept including organs-on-chips.

Keywords: Animal model, diabetes mellitus, meta-analysis, humanized animal model, pathogens, immunotherapies.

Graphical Abstract

[1]
Ericsson, A.C.; Crim, M.J.; Franklin, C.L. A brief history of animal modeling. Mo. Med., 2013, 110(3), 201-205.
[PMID: 23829102]
[2]
Denayer, T.; Stöhr, T.; Van Roy, M. Animal models in translational medicine: Validation and prediction. New Horiz. Transl. Med., 2014, 2(1), 5-11.
[http://dx.doi.org/10.1016/j.nhtm.2014.08.001]
[3]
Balls, M. The wisdom of Russell and Burch. 3. Fidelity and discrimination. Altern. Lab. Anim., 2013, 41(1), 12-14.
[http://dx.doi.org/10.1177/026119291304100120] [PMID: 23614551]
[4]
Andes, D.; Craig, W.A. Animal model pharmacokinetics and pharmacodynamics: a critical review. Int. J. Antimicrob. Agents, 2002, 19(4), 261-268.
[http://dx.doi.org/10.1016/S0924-8579(02)00022-5] [PMID: 11978497]
[5]
Zhao, M.; Lepak, A.J.; Andes, D.R. Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial agents. Bioorg. Med. Chem., 2016, 24(24), 6390-6400.
[http://dx.doi.org/10.1016/j.bmc.2016.11.008] [PMID: 27887963]
[6]
McGonigle, P.; Ruggeri, B. Animal models of human disease: challenges in enabling translation. Biochem. Pharmacol., 2014, 87(1), 162-171.
[http://dx.doi.org/10.1016/j.bcp.2013.08.006] [PMID: 23954708]
[7]
Vaddady, P.K.; Lee, R.E.; Meibohm, B. In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB. Future Med. Chem., 2010, 2(8), 1355-1369.
[http://dx.doi.org/10.4155/fmc.10.224] [PMID: 21359155]
[8]
Brochot, A.; Zamacona, M.; Stockis, A. Physiologically based pharmacokinetic/pharmacodynamic animal-to-man prediction of therapeutic dose in a model of epilepsy. Basic Clin. Pharmacol. Toxicol., 2010, 106(3), 256-262.
[http://dx.doi.org/10.1111/j.1742-7843.2009.00536.x] [PMID: 20102365]
[9]
Lodise, T.P.; Drusano, G.L. Use of pharmacokinetic/pharmacodynamic systems analyses to inform dose selection of tedizolid phosphate. Clin. Infect. Dis., 2014, 58(Suppl. 1), S28-S34.
[http://dx.doi.org/10.1093/cid/cit615] [PMID: 24343829]
[10]
Ogurtsova, K.; da Rocha Fernandes, J.D.; Huang, Y.; Linnenkamp, U.; Guariguata, L.; Cho, N.H.; Cavan, D.; Shaw, J.E.; Makaroff, L.E. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res. Clin. Pract., 2017, 128, 40-50.
[http://dx.doi.org/10.1016/j.diabres.2017.03.024] [PMID: 28437734]
[11]
Rowley, W.R.; Bezold, C.; Arikan, Y.; Byrne, E.; Krohe, S. Diabetes 2030: Insights from Yesterday, Today, and Future Trends. Popul. Health Manag., 2017, 20(1), 6-12.
[http://dx.doi.org/10.1089/pop.2015.0181] [PMID: 27124621]
[12]
Roden, M. [Diabetes mellitus: definition, classification and diagnosis Wien. Klin. Wochenschr., 2016, 128(Suppl. 2), S37-S40. [Diabetes mellitus: definition, classification and diagnosis]
[http://dx.doi.org/10.1007/s00508-015-0931-3] [PMID: 27052219]
[13]
Atkinson, M.A.; Eisenbarth, G.S. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet, 2001, 358(9277), 221-229.
[http://dx.doi.org/10.1016/S0140-6736(01)05415-0] [PMID: 11476858]
[14]
Nyaga, D.M.; Vickers, M.H.; Jefferies, C.; Perry, J.K.; O’Sullivan, J.M. The genetic architecture of type 1 diabetes mellitus. Mol. Cell. Endocrinol., 2018, 477, 70-80.
[http://dx.doi.org/10.1016/j.mce.2018.06.002] [PMID: 29913182]
[15]
Redondo, M.J.; Fain, P.R.; Eisenbarth, G.S. Genetics of type 1A diabetes. Recent Prog. Horm. Res., 2001, 56, 69-89.
[http://dx.doi.org/10.1210/rp.56.1.69] [PMID: 11237226]
[16]
Kelly, M.A.; Mijovic, C.H.; Barnett, A.H. Genetics of type 1 diabetes. Best Pract. Res. Clin. Endocrinol. Metab., 2001, 15(3), 279-291.
[http://dx.doi.org/10.1053/beem.2001.0146] [PMID: 11554771]
[17]
Slavikova, J.; Mistrova, E.; Dvorakova, M.C. Pathophysiology of diabetic cardiomyopathy. Diabetologie Metabolismus Endokrinologie Vyziva, 2018, 21(1), 21-29.
[18]
DeFronzo, R.A.; Ferrannini, E.; Groop, L.; Henry, R.R.; Herman, W.H.; Holst, J.J.; Hu, F.B.; Kahn, C.R.; Raz, I.; Shulman, G.I.; Simonson, D.C.; Testa, M.A.; Weiss, R. Type 2 diabetes mellitus. Nat. Rev. Dis. Primers, 2015, 1, 15019.
[http://dx.doi.org/10.1038/nrdp.2015.19] [PMID: 27189025]
[19]
Murai, Y.; Ohta, T.; Tadaki, H.; Miyajima, K.; Shinohara, M.; Fatchiyah, F.; Yamada, T. Assessment of Pharmacological Responses to an Anti-diabetic Drug in a New Obese Type 2 Diabetic Rat Model. Med. Arh., 2017, 71(6), 380-384.
[http://dx.doi.org/10.5455/medarh.2017.71.380-384] [PMID: 29416195]
[20]
Al-Awar, A.; Kupai, K.; Veszelka, M.; Szűcs, G.; Attieh, Z.; Murlasits, Z.; Török, S.; Pósa, A.; Varga, C. Experimental Diabetes Mellitus in Different Animal Models. J. Diabetes Res., 2016. 20169051426
[http://dx.doi.org/10.1155/2016/9051426] [PMID: 27595114]
[21]
Srinivasan, K.; Ramarao, P. Animal models in type 2 diabetes research: an overview. Indian J. Med. Res., 2007, 125(3), 451-472.
[PMID: 17496368]
[22]
King, A.J. The use of animal models in diabetes research. Br. J. Pharmacol., 2012, 166(3), 877-894.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01911.x] [PMID: 22352879]
[23]
Sasase, T.; Pezzolesi, M.G.; Yokoi, N.; Yamada, T.; Matsumoto, K. Animal models of diabetes and metabolic disease. J. Diabetes Res., 2013. 2013281928
[http://dx.doi.org/10.1155/2013/281928] [PMID: 23878821]
[24]
Mordes, J.P.; Bortell, R.; Blankenhorn, E.P.; Rossini, A.A.; Greiner, D.L. Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J., 2004, 45(3), 278-291.
[http://dx.doi.org/10.1093/ilar.45.3.278] [PMID: 15229375]
[25]
Rees, D.A.; Alcolado, J.C. Animal models of diabetes mellitus. Diabet. Med., 2005, 22(4), 359-370.
[http://dx.doi.org/10.1111/j.1464-5491.2005.01499.x] [PMID: 15787657]
[26]
Wallis, R.H.; Wang, K.; Marandi, L.; Hsieh, E.; Ning, T.; Chao, G.Y.; Sarmiento, J.; Paterson, A.D.; Poussier, P. Type 1 diabetes in the BB rat: a polygenic disease. Diabetes, 2009, 58(4), 1007-1017.
[http://dx.doi.org/10.2337/db08-1215] [PMID: 19168599]
[27]
Holmberg, R.; Refai, E.; Höög, A.; Crooke, R.M.; Graham, M.; Olivecrona, G.; Berggren, P.O.; Juntti-Berggren, L. Lowering apolipoprotein CIII delays onset of type 1 diabetes. Proc. Natl. Acad. Sci. USA, 2011, 108(26), 10685-10689.
[http://dx.doi.org/10.1073/pnas.1019553108] [PMID: 21670290]
[28]
Hartoft-Nielsen, M.L.; Rasmussen, A.K.; Bock, T.; Feldt-Rasmussen, U.; Kaas, A.; Buschard, K. Iodine and tri-iodo-thyronine reduce the incidence of type 1 diabetes mellitus in the autoimmune prone BB rats. Autoimmunity, 2009, 42(2), 131-138.
[http://dx.doi.org/10.1080/08916930802438774] [PMID: 19021014]
[29]
Zhang, W.; Kamiya, H.; Ekberg, K.; Wahren, J.; Sima, A.A. C-peptide improves neuropathy in type 1 diabetic BB/Wor-rats. Diabetes Metab. Res. Rev., 2007, 23(1), 63-70.
[http://dx.doi.org/10.1002/dmrr.672] [PMID: 16845685]
[30]
Jörns, A.; Günther, A.; Hedrich, H.J.; Wedekind, D.; Tiedge, M.; Lenzen, S. Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm rat. Diabetes, 2005, 54(7), 2041-2052.
[http://dx.doi.org/10.2337/diabetes.54.7.2041] [PMID: 15983205]
[31]
Lenzen, S.; Tiedge, M.; Elsner, M.; Lortz, S.; Weiss, H.; Jörns, A.; Klöppel, G.; Wedekind, D.; Prokop, C.M.; Hedrich, H.J. The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes mellitus. Diabetologia, 2001, 44(9), 1189-1196.
[http://dx.doi.org/10.1007/s001250100625] [PMID: 11596676]
[32]
Mathews, C.E. Utility of murine models for the study of spontaneous autoimmune type 1 diabetes. Pediatr. Diabetes, 2005, 6(3), 165-177.
[http://dx.doi.org/10.1111/j.1399-543X.2005.00123.x] [PMID: 16109074]
[33]
Jörns, A.; Rath, K.J.; Terbish, T.; Arndt, T.; Meyer Zu Vilsendorf, A.; Wedekind, D.; Hedrich, H.J.; Lenzen, S. Diabetes prevention by immunomodulatory FTY720 treatment in the LEW.1AR1-iddm rat despite immune cell activation. Endocrinology, 2010, 151(8), 3555-3565.
[http://dx.doi.org/10.1210/en.2010-0202] [PMID: 20501676]
[34]
Arndt, T.; Wedekind, D.; Weiss, H.; Tiedge, M.; Lenzen, S.; Hedrich, H.J.; Jörns, A. Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes. Diabetologia, 2009, 52(7), 1381-1390.
[http://dx.doi.org/10.1007/s00125-009-1348-1] [PMID: 19367386]
[35]
Jörns, A.; Kubat, B.; Tiedge, M.; Wedekind, D.; Hedrich, H.J.; Klöppel, G.; Lenzen, S. Pathology of the pancreas and other organs in the diabetic LEW.1AR1/Ztm- iddm rat, a new model of spontaneous insulin-dependent diabetes mellitus. Virchows Arch., 2004, 444(2), 183-189.
[http://dx.doi.org/10.1007/s00428-003-0956-2] [PMID: 14735361]
[36]
Peschke, E.; Hofmann, K.; Bähr, I.; Streck, S.; Albrecht, E.; Wedekind, D.; Mühlbauer, E. The insulin-melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus). Diabetologia, 2011, 54(7), 1831-1840.
[http://dx.doi.org/10.1007/s00125-011-2138-0] [PMID: 21491159]
[37]
Yang, Z.; Chen, M.; Fialkow, L.B.; Ellett, J.D.; Wu, R.; Brinkmann, V.; Nadler, J.L.; Lynch, K.R. The immune modulator FYT720 prevents autoimmune diabetes in nonobese diabetic mice. Clin. Immunol., 2003, 107(1), 30-35.
[http://dx.doi.org/10.1016/S1521-6616(02)00054-2] [PMID: 12738247]
[38]
Maki, T.; Gottschalk, R.; Ogawa, N.; Monaco, A.P. Prevention and cure of autoimmune diabetes in nonobese diabetic mice by continuous administration of FTY720. Transplantation, 2005, 79(9), 1051-1055.
[http://dx.doi.org/10.1097/01.TP.0000161220.87548.EE] [PMID: 15880042]
[39]
Hanafusa, T.; Miyagawa, J.; Nakajima, H.; Tomita, K.; Kuwajima, M.; Matsuzawa, Y.; Tarui, S. The NOD mouse. Diabetes Res. Clin. Pract., (24), S307-S311.1994.
[http://dx.doi.org/10.1016/0168-8227(94)90267-4]
[40]
Yoon, J.W.; Jun, H.S. Viruses in type 1 diabetes: brief review. ILAR J., 2004, 45(3), 343-348.
[http://dx.doi.org/10.1093/ilar.45.3.343] [PMID: 15229381]
[41]
Jansen, A.; Homo-Delarche, F.; Hooijkaas, H.; Leenen, P.J.; Dardenne, M.; Drexhage, H.A. Immunohistochemical characterization of monocytes-macrophages and dendritic cells involved in the initiation of the insulitis and beta-cell destruction in NOD mice. Diabetes, 1994, 43(5), 667-675.
[http://dx.doi.org/10.2337/diab.43.5.667] [PMID: 8168644]
[42]
Bouma, G.; Coppens, J.M.; Mourits, S.; Nikolic, T.; Sozzani, S.; Drexhage, H.A.; Versnel, M.A. Evidence for an enhanced adhesion of DC to fibronectin and a role of CCL19 and CCL21 in the accumulation of DC around the pre-diabetic islets in NOD mice. Eur. J. Immunol., 2005, 35(8), 2386-2396.
[http://dx.doi.org/10.1002/eji.200526251] [PMID: 16047341]
[43]
Diana, J.; Simoni, Y.; Furio, L.; Beaudoin, L.; Agerberth, B.; Barrat, F.; Lehuen, A. Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes. Nat. Med., 2013, 19(1), 65-73.
[http://dx.doi.org/10.1038/nm.3042] [PMID: 23242473]
[44]
Willcox, A.; Richardson, S.J.; Bone, A.J.; Foulis, A.K.; Morgan, N.G. Analysis of islet inflammation in human type 1 diabetes. Clin. Exp. Immunol., 2009, 155(2), 173-181.
[http://dx.doi.org/10.1111/j.1365-2249.2008.03860.x] [PMID: 19128359]
[45]
Miyazaki, A.; Hanafusa, T.; Yamada, K.; Miyagawa, J.; Fujino-Kurihara, H.; Nakajima, H.; Nonaka, K.; Tarui, S. Predominance of T lymphocytes in pancreatic islets and spleen of pre-diabetic non-obese diabetic (NOD) mice: a longitudinal study. Clin. Exp. Immunol., 1985, 60(3), 622-630.
[PMID: 3160515]
[46]
Pearson, J.A.; Wong, F.S.; Wen, L. The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes. J. Autoimmun., 2016, 66, 76-88.
[http://dx.doi.org/10.1016/j.jaut.2015.08.019] [PMID: 26403950]
[47]
Noble, J.A.; Erlich, H.A. Genetics of type 1 diabetes. Cold Spring Harb. Perspect. Med., 2012, 2(1)a007732
[http://dx.doi.org/10.1101/cshperspect.a007732] [PMID: 22315720]
[48]
Chen, Y.G.; Mathews, C.E.; Driver, J.P. The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future. Front. Endocrinol. (Lausanne), 2018, 9, 51.
[http://dx.doi.org/10.3389/fendo.2018.00051] [PMID: 29527189]
[49]
Todd, J.A.; Wicker, L.S. Genetic protection from the inflammatory disease type 1 diabetes in humans and animal models. Immunity, 2001, 15(3), 387-395.
[http://dx.doi.org/10.1016/S1074-7613(01)00202-3] [PMID: 11567629]
[50]
von Herrath, M.; Filippi, C.; Coppieters, K. How viral infections enhance or prevent type 1 diabetes-from mouse to man. J. Med. Virol., 2011, 83(9), 1672.
[http://dx.doi.org/10.1002/jmv.22063] [PMID: 21739461]
[51]
Yang, Y.; Santamaria, P. Lessons on autoimmune diabetes from animal models. Clin. Sci. (Lond.), 2006, 110(6), 627-639.
[http://dx.doi.org/10.1042/CS20050330] [PMID: 16689681]
[52]
Mathews, C.E.; Langley, S.H.; Leiter, E.H. New mouse model to study islet transplantation in insulin-dependent diabetes mellitus. Transplantation, 2002, 73(8), 1333-1336.
[http://dx.doi.org/10.1097/00007890-200204270-00024] [PMID: 11981430]
[53]
Drel, V.R.; Pacher, P.; Stavniichuk, R.; Xu, W.; Zhang, J.; Kuchmerovska, T.M.; Slusher, B.; Obrosova, I.G. Poly(ADP-ribose)polymerase inhibition counteracts renal hypertrophy and multiple manifestations of peripheral neuropathy in diabetic Akita mice. Int. J. Mol. Med., 2011, 28(4), 629-635.
[PMID: 21617845]
[54]
Zhou, C.; Pridgen, B.; King, N.; Xu, J.; Breslow, J.L. Hyperglycemic Ins2AkitaLdlr/ mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular disease. J. Lipid Res., 2011, 52(8), 1483-1493.
[http://dx.doi.org/10.1194/jlr.M014092] [PMID: 21606463]
[55]
Gurley, S.B.; Clare, S.E.; Snow, K.P.; Hu, A.; Meyer, T.W.; Coffman, T.M. Impact of genetic background on nephropathy in diabetic mice. Am. J. Physiol. Renal Physiol., 2006, 290(1), F214-F222.
[http://dx.doi.org/10.1152/ajprenal.00204.2005] [PMID: 16118394]
[56]
Tyrberg, B.; Andersson, A.; Borg, L.A. Species differences in susceptibility of transplanted and cultured pancreatic islets to the beta-cell toxin alloxan. Gen. Comp. Endocrinol., 2001, 122(3), 238-251.
[http://dx.doi.org/10.1006/gcen.2001.7638] [PMID: 11356036]
[57]
Dufrane, D.; van Steenberghe, M.; Guiot, Y.; Goebbels, R.M.; Saliez, A.; Gianello, P. Streptozotocin-induced diabetes in large animals (pigs/primates): role of GLUT2 transporter and beta-cell plasticity. Transplantation, 2006, 81(1), 36-45.
[http://dx.doi.org/10.1097/01.tp.0000189712.74495.82] [PMID: 16421474]
[58]
Eizirik, D.L.; Pipeleers, D.G.; Ling, Z.; Welsh, N.; Hellerström, C.; Andersson, A. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury. Proc. Natl. Acad. Sci. USA, 1994, 91(20), 9253-9256.
[http://dx.doi.org/10.1073/pnas.91.20.9253] [PMID: 7937750]
[59]
Lenzen, S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia, 2008, 51(2), 216-226.
[http://dx.doi.org/10.1007/s00125-007-0886-7] [PMID: 18087688]
[60]
Wise, M.H.; Gordon, C.; Johnson, R.W. Intraportal autotransplantation of cryopreserved porcine islets of Langerhans. Cryobiology, 1985, 22(4), 359-366.
[http://dx.doi.org/10.1016/0011-2240(85)90183-X] [PMID: 3161702]
[61]
He, S.; Chen, Y.; Wei, L.; Jin, X.; Zeng, L.; Ren, Y.; Zhang, J.; Wang, L.; Li, H.; Lu, Y.; Cheng, J. Treatment and risk factor analysis of hypoglycemia in diabetic rhesus monkeys. Exp. Biol. Med. (Maywood), 2011, 236(2), 212-218.
[http://dx.doi.org/10.1258/ebm.2010.010208] [PMID: 21321318]
[62]
Wei, L.; Lu, Y.; He, S.; Jin, X.; Zeng, L.; Zhang, S.; Chen, Y.; Tian, B.; Mai, G.; Yang, G.; Zhang, J.; Wang, L.; Li, H.; Markmann, J.F.; Cheng, J.; Deng, S. Induction of diabetes with signs of autoimmunity in primates by the injection of multiple-low-dose streptozotocin. Biochem. Biophys. Res. Commun., 2011, 412(2), 373-378.
[http://dx.doi.org/10.1016/j.bbrc.2011.07.105] [PMID: 21821007]
[63]
Moon, C.H.; Jung, Y.S.; Lee, S.H.; Baik, E.J. Protein kinase C inhibitors abolish the increased resistance of diabetic rat heart to ischemia-reperfusion injury. Jpn. J. Physiol., 1999, 49(5), 409-415.
[http://dx.doi.org/10.2170/jjphysiol.49.409] [PMID: 10603424]
[64]
Chen, H.; Shen, W.L.; Wang, X.H.; Chen, H.Z.; Gu, J.Z.; Fu, J.; Ni, Y.F.; Gao, P.J.; Zhu, D.L.; Higashino, H. Paradoxically enhanced heart tolerance to ischaemia in type 1 diabetes and role of increased osmolarity. Clin. Exp. Pharmacol. Physiol., 2006, 33(10), 910-916.
[http://dx.doi.org/10.1111/j.1440-1681.2006.04463.x] [PMID: 17002667]
[65]
Ravingerova, T.; Matejikova, J.; Pancza, D.; Kolar, F. Reduced susceptibility to ischemia-induced arrhythmias in the preconditioned rat heart is independent of PI3-kinase/Akt. Physiol. Res., 2009, 58(3), 443-447.
[PMID: 19627174]
[66]
Chen, H.; Charlat, O.; Tartaglia, L.A.; Woolf, E.A.; Weng, X.; Ellis, S.J.; Lakey, N.D.; Culpepper, J.; Moore, K.J.; Breitbart, R.E.; Duyk, G.M.; Tepper, R.I.; Morgenstern, J.P. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell, 1996, 84(3), 491-495.
[http://dx.doi.org/10.1016/S0092-8674(00)81294-5] [PMID: 8608603]
[67]
Gault, V.A.; Kerr, B.D.; Harriott, P.; Flatt, P.R. Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. Clin. Sci. (Lond.), 2011, 121(3), 107-117.
[http://dx.doi.org/10.1042/CS20110006] [PMID: 21332446]
[68]
Yoshida, S.; Tanaka, H.; Oshima, H.; Yamazaki, T.; Yonetoku, Y.; Ohishi, T.; Matsui, T.; Shibasaki, M. AS1907417, a novel GPR119 agonist, as an insulinotropic and β-cell preservative agent for the treatment of type 2 diabetes. Biochem. Biophys. Res. Commun., 2010, 400(4), 745-751.
[http://dx.doi.org/10.1016/j.bbrc.2010.08.141] [PMID: 20816753]
[69]
Park, J.S.; Rhee, S.D.; Kang, N.S.; Jung, W.H.; Kim, H.Y.; Kim, J.H.; Kang, S.K.; Cheon, H.G.; Ahn, J.H.; Kim, K.Y. Anti-diabetic and anti-adipogenic effects of a novel selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344). Biochem. Pharmacol., 2011, 81(8), 1028-1035.
[http://dx.doi.org/10.1016/j.bcp.2011.01.020] [PMID: 21315688]
[70]
Lindström, P. The physiology of obese-hyperglycemic mice. [ob/ob mice] ScientificWorldJournal, 2007, 7, 666-685. [ob/ob mice]
[http://dx.doi.org/ 10.1100/tsw.2007.117] [PMID: 17619751]
[71]
Chehab, F.F.; Lim, M.E.; Lu, R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat. Genet., 1996, 12(3), 318-320.
[http://dx.doi.org/10.1038/ng0396-318] [PMID: 8589726]
[72]
Bock, T.; Pakkenberg, B.; Buschard, K. Increased islet volume but unchanged islet number in ob/ob mice. Diabetes, 2003, 52(7), 1716-1722.
[http://dx.doi.org/10.2337/diabetes.52.7.1716] [PMID: 12829638]
[73]
Lavine, R.L.; Voyles, N.; Perrino, P.V.; Recant, L. Functional abnormalities of islets of Langerhans of obese hyperglycemic mouse. Am. J. Physiol., 1977, 233(2), E86-E90.
[PMID: 329686]
[74]
Coleman, D.L. Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia, 1978, 14(3), 141-148.
[http://dx.doi.org/10.1007/BF00429772] [PMID: 350680]
[75]
Asensio, C.; Cettour-Rose, P.; Theander-Carrillo, C.; Rohner-Jeanrenaud, F.; Muzzin, P. Changes in glycemia by leptin administration or high- fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. Endocrinology, 2004, 145(5), 2206-2213.
[http://dx.doi.org/10.1210/en.2003-1679] [PMID: 14962997]
[76]
Zhang, B.; Salituro, G.; Szalkowski, D.; Li, Z.; Zhang, Y.; Royo, I.; Vilella, D.; Díez, M.T.; Pelaez, F.; Ruby, C.; Kendall, R.L.; Mao, X.; Griffin, P.; Calaycay, J.; Zierath, J.R.; Heck, J.V.; Smith, R.G.; Moller, D.E. Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science, 1999, 284(5416), 974-977.
[http://dx.doi.org/10.1126/science.284.5416.974] [PMID: 10320380]
[77]
Chakrabarti, R.; Vikramadithyan, R.K.; Misra, P.; Hiriyan, J.; Raichur, S.; Damarla, R.K.; Gershome, C.; Suresh, J.; Rajagopalan, R. Ragaglitazar: a novel PPAR alpha PPAR gamma agonist with potent lipid-lowering and insulin-sensitizing efficacy in animal models. Br. J. Pharmacol., 2003, 140(3), 527-537.
[http://dx.doi.org/10.1038/sj.bjp.0705463] [PMID: 12970088]
[78]
Hummel, K.P.; Dickie, M.M.; Coleman, D.L. Diabetes, a new mutation in the mouse. Science, 1966, 153(3740), 1127-1128.
[http://dx.doi.org/10.1126/science.153.3740.1127] [PMID: 5918576]
[79]
Phillips, M.S.; Liu, Q.; Hammond, H.A.; Dugan, V.; Hey, P.J.; Caskey, C.J.; Hess, J.F. Leptin receptor missense mutation in the fatty Zucker rat. Nat. Genet., 1996, 13(1), 18-19.
[http://dx.doi.org/10.1038/ng0596-18] [PMID: 8673096]
[80]
Tokuyama, Y.; Sturis, J.; DePaoli, A.M.; Takeda, J.; Stoffel, M.; Tang, J.; Sun, X.; Polonsky, K.S.; Bell, G.I. Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat. Diabetes, 1995, 44(12), 1447-1457.
[http://dx.doi.org/10.2337/diab.44.12.1447] [PMID: 7589853]
[81]
Lee, Y.; Hirose, H.; Zhou, Y.T.; Esser, V.; McGarry, J.D.; Unger, R.H. Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM. Diabetes, 1997, 46(3), 408-413.
[http://dx.doi.org/10.2337/diab.46.3.408] [PMID: 9032096]
[82]
Shimabukuro, M.; Zhou, Y.T.; Levi, M.; Unger, R.H. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc. Natl. Acad. Sci. USA, 1998, 95(5), 2498-2502.
[http://dx.doi.org/10.1073/pnas.95.5.2498] [PMID: 9482914]
[83]
Shimabukuro, M.; Higa, M.; Zhou, Y.T.; Wang, M.Y.; Newgard, C.B.; Unger, R.H. Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression. J. Biol. Chem., 1998, 273(49), 32487-32490.
[http://dx.doi.org/10.1074/jbc.273.49.32487] [PMID: 9829981]
[84]
Hemmes, R.B.; Schoch, R. High dosage testosterone propionate induces copulatory behavior in the obese male Zucker rat. Physiol. Behav., 1988, 43(3), 321-324.
[http://dx.doi.org/10.1016/0031-9384(88)90195-3] [PMID: 3174844]
[85]
Shibata, T.; Takeuchi, S.; Yokota, S.; Kakimoto, K.; Yonemori, F.; Wakitani, K. Effects of peroxisome proliferator-activated receptor-alpha and -gamma agonist, JTT-501, on diabetic complications in Zucker diabetic fatty rats. Br. J. Pharmacol., 2000, 130(3), 495-504.
[http://dx.doi.org/10.1038/sj.bjp.0703328] [PMID: 10821776]
[86]
Clohessy, J.G.; Pandolfi, P.P. Mouse hospital and co-clinical trial project--from bench to bedside. Nat. Rev. Clin. Oncol., 2015, 12(8), 491-498.
[http://dx.doi.org/10.1038/nrclinonc.2015.62] [PMID: 25895610]
[87]
Clohessy, J.G.; Pandolfi, P.P. The Mouse Hospital and Its Integration in Ultra-Precision Approaches to Cancer Care. Front. Oncol., 2018, 8, 340.
[http://dx.doi.org/10.3389/fonc.2018.00340] [PMID: 30211119]
[88]
Yang, F.; Stewart, M.; Ye, J.; DeMets, D. Type 2 diabetes mellitus development programs in the new regulatory environment with cardiovascular safety requirements. Diabetes Metab. Syndr. Obes., 2015, 8, 315-325.
[http://dx.doi.org/10.2147/DMSO.S84005] [PMID: 26229496]
[89]
Brass, E.P. The Food and Drug Administration and the Future of Drug Development for the Treatment of Diabetes. Diabetes Spectr., 2014, 27(2), 75-77.
[http://dx.doi.org/10.2337/diaspect.27.2.75] [PMID: 26246760]
[90]
Smith, R.J.; Goldfine, A.B.; Hiatt, W.R. Evaluating the Cardiovascular Safety of New Medications for Type 2 Diabetes: Time to Reassess? Diabetes Care, 2016, 39(5), 738-742.
[http://dx.doi.org/10.2337/dc15-2237] [PMID: 27208377]
[91]
Garcia-Verdugo, R.; Erbach, M.; Schnell, O. Need for Outcome Scenario Analysis of Clinical Trials in Diabetes. J. Diabetes Sci. Technol., 2017, 11(2), 327-334.
[http://dx.doi.org/10.1177/1932296816670925] [PMID: 27707913]
[92]
Derscheid, R.J.; Ackermann, M.R. Perinatal lamb model of respiratory syncytial virus (RSV) infection. Viruses, 2012, 4(10), 2359-2378.
[http://dx.doi.org/10.3390/v4102359] [PMID: 23202468]
[93]
Sams-Dodd, F. Strategies to optimize the validity of disease models in the drug discovery process. Drug Discov. Today, 2006, 11(7-8), 355-363.
[http://dx.doi.org/10.1016/j.drudis.2006.02.005] [PMID: 16580978]
[94]
Cavagnaro, J.; Silva Lima, B. Regulatory acceptance of animal models of disease to support clinical trials of medicines and advanced therapy medicinal products. Eur. J. Pharmacol., 2015, 759, 51-62.
[http://dx.doi.org/10.1016/j.ejphar.2015.03.048] [PMID: 25814257]
[95]
Pinger, C.W.; Entwistle, K.E.; Bell, T.M.; Liu, Y.; Spence, D.M. C-Peptide replacement therapy in type 1 diabetes: are we in the trough of disillusionment? Mol. Biosyst., 2017, 13(8), 1432-1437.
[http://dx.doi.org/10.1039/C7MB00199A] [PMID: 28685788]
[96]
Nissen, S.E.; Wolski, K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N. Engl. J. Med., 2007, 356(24), 2457-2471.
[http://dx.doi.org/10.1056/NEJMoa072761] [PMID: 17517853]
[97]
Cheng, D.; Gao, H.; Li, W. Long-term risk of rosiglitazone on cardiovascular events - a systematic review and meta-analysis. Endokrynol. Pol., 2018, 69(4), 381-394.
[PMID: 29952413]
[98]
Singh, S.; Loke, Y.K.; Furberg, C.D. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA, 2007, 298(10), 1189-1195.
[http://dx.doi.org/10.1001/jama.298.10.1189] [PMID: 17848653]
[99]
Blind, E.; Dunder, K.; de Graeff, P.A.; Abadie, E. Rosiglitazone: a European regulatory perspective. Diabetologia, 2011, 54(2), 213-218.
[http://dx.doi.org/10.1007/s00125-010-1992-5] [PMID: 21153629]
[100]
Cummings, J.L.; Morstorf, T.; Zhong, K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res. Ther., 2014, 6(4), 37.
[http://dx.doi.org/10.1186/alzrt269] [PMID: 25024750]
[101]
van der Worp, H.B.; Howells, D.W.; Sena, E.S.; Porritt, M.J.; Rewell, S.; O’Collins, V.; Macleod, M.R. Can animal models of disease reliably inform human studies? PLoS Med., 2010, 7(3)e1000245
[http://dx.doi.org/10.1371/journal.pmed.1000245] [PMID: 20361020]
[102]
Tyagi, P.; Pechenov, S.; Anand Subramony, J. Oral peptide delivery: Translational challenges due to physiological effects. J. Control. Release, 2018, 287, 167-176.
[http://dx.doi.org/10.1016/j.jconrel.2018.08.032] [PMID: 30145135]
[103]
Hooper, S.B.; Te Pas, A.B.; Polglase, G.R.; Wyckoff, M. Animal models in neonatal resuscitation research: What can they teach us? Semin. Fetal Neonatal Med., 2018, 23(5), 300-305.
[http://dx.doi.org/10.1016/j.siny.2018.07.002] [PMID: 30001819]
[104]
Koch, J.C.; Tatenhorst, L.; Roser, A.E.; Saal, K.A.; Tönges, L.; Lingor, P. ROCK inhibition in models of neurodegeneration and its potential for clinical translation. Pharmacol. Ther., 2018, 189, 1-21.
[http://dx.doi.org/10.1016/j.pharmthera.2018.03.008] [PMID: 29621594]
[105]
Eicher, A.K.; Berns, H.M.; Wells, J.M. Translating Developmental Principles to Generate Human Gastric Organoids. Cell. Mol. Gastroenterol. Hepatol., 2018, 5(3), 353-363.
[http://dx.doi.org/10.1016/j.jcmgh.2017.12.014] [PMID: 29552623]
[106]
Kenney, L.L.; Shultz, L.D.; Greiner, D.L.; Brehm, M.A. Humanized Mouse Models for Transplant Immunology. Am. J. Transplant., 2016, 16(2), 389-397.
[http://dx.doi.org/10.1111/ajt.13520] [PMID: 26588186]
[107]
Wege, A.K. Humanized Mouse Models for the Preclinical Assessment of Cancer Immunotherapy. BioDrugs, 2018, 32(3), 245-266.
[http://dx.doi.org/10.1007/s40259-018-0275-4] [PMID: 29589229]
[108]
Ito, R.; Takahashi, T.; Katano, I.; Ito, M. Current advances in humanized mouse models. Cell. Mol. Immunol., 2012, 9(3), 208-214.
[http://dx.doi.org/10.1038/cmi.2012.2] [PMID: 22327211]
[109]
Abaci, H.E.; Shuler, M.L. Human-on-a-chip design strategies and principles for physiologically based pharmacokinetics/pharmacodynamics modeling. Integr. Biol., 2015, 7(4), 383-391.
[http://dx.doi.org/10.1039/C4IB00292J] [PMID: 25739725]
[110]
Brown, J.A.; Codreanu, S.G.; Shi, M.; Sherrod, S.D.; Markov, D.A.; Neely, M.D.; Britt, C.M.; Hoilett, O.S.; Reiserer, R.S.; Samson, P.C.; McCawley, L.J.; Webb, D.J.; Bowman, A.B.; McLean, J.A.; Wikswo, J.P. Metabolic consequences of inflammatory disruption of the blood-brain barrier in an organ-on-chip model of the human neurovascular unit. J. Neuroinflammation, 2016, 13(1), 306.
[http://dx.doi.org/10.1186/s12974-016-0760-y] [PMID: 27955696]
[111]
Dodson, K.H.; Echevarria, F.D.; Li, D.; Sappington, R.M.; Edd, J.F. Retina-on-a-chip: a microfluidic platform for point access signaling studies. Biomed. Microdevices, 2015, 17(6), 114.
[http://dx.doi.org/10.1007/s10544-015-0019-x] [PMID: 26559199]
[112]
Dorval, T.; Chanrion, B.; Cattin, M.E.; Stephan, J.P. Filling the drug discovery gap: is high-content screening the missing link? Curr. Opin. Pharmacol., 2018, 42, 40-45.
[http://dx.doi.org/10.1016/j.coph.2018.07.002] [PMID: 30032033]
[113]
Hachey, S.J.; Hughes, C.C.W. Applications of tumor chip technology. Lab Chip, 2018, 18(19), 2893-2912.
[http://dx.doi.org/10.1039/C8LC00330K] [PMID: 30156248]
[114]
Irimia, D.; Wang, X. Inflammation-on-a-Chip: Probing the Immune System Ex Vivo. Trends Biotechnol., 2018, 36(9), 923-937.
[http://dx.doi.org/10.1016/j.tibtech.2018.03.011] [PMID: 29728272]
[115]
Kodzius, R.; Schulze, F.; Gao, X.; Schneider, M.R. Organ-on-Chip Technology: Current State and Future Developments. Genes (Basel), 2017, 8(10)E266
[http://dx.doi.org/10.3390/genes8100266] [PMID: 29019963]
[116]
Mandenius, C.F. Conceptual Design of Micro-Bioreactors and Organ-on-Chips for Studies of Cell Cultures. Bioengineering (Basel), 2018, 5(3)E56
[http://dx.doi.org/10.3390/bioengineering5030056] [PMID: 30029542]
[117]
Miranda, C.C.; Fernandes, T.G.; Diogo, M.M.; Cabral, J.M.S. Towards Multi-Organoid Systems for Drug Screening Applications. Bioengineering (Basel), 2018, 5(3)E49
[http://dx.doi.org/10.3390/bioengineering5030049] [PMID: 29933623]
[118]
Nikolic, M.; Sustersic, T.; Filipovic, N. In vitro Models and On-Chip Systems: Biomaterial Interaction Studies With Tissues Generated Using Lung Epithelial and Liver Metabolic Cell Lines. Front. Bioeng. Biotechnol., 2018, 6, 120.
[http://dx.doi.org/10.3389/fbioe.2018.00120] [PMID: 30234106]
[119]
Rothbauer, M.; Rosser, J.M.; Zirath, H.; Ertl, P. Tomorrow today: organ-on-a-chip advances towards clinically relevant pharmaceutical and medical in vitro models. Curr. Opin. Biotechnol., 2019, 55, 81-86.
[http://dx.doi.org/10.1016/j.copbio.2018.08.009] [PMID: 30189349]
[120]
Wikswo, J.P.; Block, F.E., III; Cliffel, D.E.; Goodwin, C.R.; Marasco, C.C.; Markov, D.A.; McLean, D.L.; McLean, J.A.; McKenzie, J.R.; Reiserer, R.S.; Samson, P.C.; Schaffer, D.K.; Seale, K.T.; Sherrod, S.D. Engineering challenges for instrumenting and controlling integrated organ-on-chip systems. IEEE Trans. Biomed. Eng., 2013, 60(3), 682-690.
[http://dx.doi.org/10.1109/TBME.2013.2244891] [PMID: 23380852]
[121]
Wikswo, J.P.; Curtis, E.L.; Eagleton, Z.E.; Evans, B.C.; Kole, A.; Hofmeister, L.H.; Matloff, W.J. Scaling and systems biology for integrating multiple organs-on-a-chip. Lab Chip, 2013, 13(18), 3496-3511.
[http://dx.doi.org/10.1039/c3lc50243k] [PMID: 23828456]
[122]
Wikswo, J.P. Looking to the future of organs-on-chips: interview with Professor John Wikswo. Future Sci. OA, 2017, 3(2)FSO163
[http://dx.doi.org/10.4155/fsoa-2016-0085] [PMID: 28670462]
[123]
Wnorowski, A.; Yang, H.; Wu, J.C. Progress, obstacles, and limitations in the use of stem cells in organ-on-a-chip models. dv. Drug Deliv. Rev., 2018, S0169-409X(18), 30132-7.
[http://dx.doi.org/10.1016/j.addr.2018.06.001] [PMID: 29885330]
[124]
Kersten, K.; de Visser, K.E.; van Miltenburg, M.H.; Jonkers, J. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol. Med., 2017, 9(2), 137-153.
[http://dx.doi.org/10.15252/emmm.201606857] [PMID: 28028012]
[125]
Uhl, E.W.; Warner, N.J. Mouse Models as Predictors of Human Responses: Evolutionary Medicine. Curr. Pathobiol. Rep., 2015, 3(3), 219-223.
[http://dx.doi.org/10.1007/s40139-015-0086-y] [PMID: 26246962]
[126]
Luce, S.; Guinoiseau, S.; Gadault, A.; Letourneur, F.; Blondeau, B.; Nitschke, P.; Pasmant, E.; Vidaud, M.; Lemonnier, F.; Boitard, C. Humanized Mouse Model to Study Type 1 Diabetes. Diabetes, 2018, 67(9), 1816-1829.
[http://dx.doi.org/10.2337/db18-0202] [PMID: 29967002]
[127]
Walsh, N.C.; Kenney, L.L.; Jangalwe, S.; Aryee, K.E.; Greiner, D.L.; Brehm, M.A.; Shultz, L.D. Humanized Mouse Models of Clinical Disease. Annu. Rev. Pathol., 2017, 12, 187-215.
[http://dx.doi.org/10.1146/annurev-pathol-052016-100332] [PMID: 27959627]
[128]
Puca, L.; Bareja, R.; Prandi, D.; Shaw, R.; Benelli, M.; Karthaus, W.R.; Hess, J.; Sigouros, M.; Donoghue, A.; Kossai, M.; Gao, D.; Cyrta, J.; Sailer, V.; Vosoughi, A.; Pauli, C.; Churakova, Y.; Cheung, C.; Deonarine, L.D.; McNary, T.J.; Rosati, R.; Tagawa, S.T.; Nanus, D.M.; Mosquera, J.M.; Sawyers, C.L.; Chen, Y.; Inghirami, G.; Rao, R.A.; Grandori, C.; Elemento, O.; Sboner, A.; Demichelis, F.; Rubin, M.A.; Beltran, H. Patient derived organoids to model rare prostate cancer phenotypes. Nat. Commun., 2018, 9(1), 2404.
[http://dx.doi.org/10.1038/s41467-018-04495-z] [PMID: 29921838]
[129]
Ibarrola-Villava, M.; Cervantes, A.; Bardelli, A. Preclinical models for precision oncology. Biochim. Biophys. Acta Rev. Cancer, 2018, 1870(2), 239-246.
[http://dx.doi.org/10.1016/j.bbcan.2018.06.004] [PMID: 29959990]
[130]
Garralda, E.; Paz, K.; López-Casas, P.P.; Jones, S.; Katz, A.; Kann, L.M.; López-Rios, F.; Sarno, F.; Al-Shahrour, F.; Vasquez, D.; Bruckheimer, E.; Angiuoli, S.V.; Calles, A.; Diaz, L.A.; Velculescu, V.E.; Valencia, A.; Sidransky, D.; Hidalgo, M. Integrated next-generation sequencing and avatar mouse models for personalized cancer treatment. Clin. Cancer Res., 2014, 20(9), 2476-2484.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3047] [PMID: 24634382]
[131]
Malaney, P.; Nicosia, S.V.; Davé, V. One mouse, one patient paradigm: New avatars of personalized cancer therapy. Cancer Lett., 2014, 344(1), 1-12.
[http://dx.doi.org/10.1016/j.canlet.2013.10.010] [PMID: 24157811]
[132]
Zayed, A.A.; Mandrekar, S.J.; Haluska, P. Molecular and clinical implementations of ovarian cancer mouse avatar models. Linchuang Zhongliuxue Zazhi, 2015, 4(3), 30.
[PMID: 26408297]
[133]
Saadat, V.; Tsugita, R. Device for sensing parameters of a hollow body organ. U.S. Patent 6,939,313 B2. 2005.
[134]
Wikswo, J.P.; Samson, P.C.; Emmanuel, F.; Reiserer, R.S.; Parker, K.K.; McLean, J.A.; McCawley, L.J.; Markov, D.; Levner, D.; Ingber, D.E.; Hamilton, G.A.; Goss, J.A.; Cunningham, R.; Cliffel, D.E.; McKenzie, R.J.; Bahinski, A.; Hinojosa, C.D. Integrated human organ-on-chip microphysiological systems. U.S. Patent 9,725,687 B2. 2017.
[135]
Gonda, S.R.; Chang, R.C.; Starly, B.; Culbertson, C.; Holtorf, H.L.; Sun, W.; Leslie, J. Micro-organ device. U.S. Patent 2013/0109594 A1 2013.
[136]
Gatenholm, P. Three-dimensional bioprinting of biosynthetic cellulose (BC) implants and scaffolds for tissue engineering. Patent 8,691.974 B2. 2014.
[137]
Ingber, D.E.; Parker, K.K.; Hamilton, G.A.; Bahinski, A. Organ chips and uses thereof. U.S. Patent 10, 087, 422 B2. 2018.
[138]
Andreassen, S.; Falck, B.; Olesen, K.G. Diagnostic function of the microhuman prototype of the expert system--MUNIN. Electroencephalogr. Clin. Neurophysiol., 1992, 85(2), 143-157.
[http://dx.doi.org/10.1016/0168-5597(92)90080-U] [PMID: 1373367]

© 2024 Bentham Science Publishers | Privacy Policy