Ayobahan SU, Eilebrecht S, Baumann L, Teigeler M, Hollert H, Kalkhof S, et al. Brown DR, Samsa LA, Qian L, Liu J. The Zebrafish Information Network (ZFIN): the zebrafish model organism database. Exclusive human factors affecting metabolism such as lifestyle, behavioral, and socioeconomic factors cannot be replicated in zebrafish. These fish also have a rapid maturation time which helps with reducing total research duration. (2018) 6:91. doi: 10.3389/fcell.2018.00091, 10. Besides, there is a correlation between intestinal microbiota and obesity and its related disorders like NAFLD (13, 91). (2018) 9:23443. Moreover, it has contributed to metabolic diseases researches including pathologic conditions in pancreas and liver by making the identification of signals and regeneration mechanisms easier. Lu J, Xia Q, Zhou Q. Gerontology. Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism. Personalized medicine can significantly increase patient compliance with the drug and subsequently ensure better patient care while reducing costs (3). It produces neurotransmitters such as serotonin, gamma-amino butyric acid (GABA), dopamine, histamine, etc. (2017) 63:5809. Schenk H, Mller-Deile J, Kinast M, Schiffer M. Disease modeling in genetic kidney diseases: zebrafish. No use, distribution or reproduction is permitted which does not comply with these terms. Molinari E, Sayer JA. (2008) 149:601827. Herzog W, Sonntag C, von der Hardt S, Roehl HH, Varga ZM, Hammerschmidt M. Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis. doi: 10.1016/j.beem.2018.03.010, 45. There are more obstacles in using zebrafish as a metabolic disease model than in other disorders like cardiovascular studies. Hereupon, in order to achieve a better understanding of associations between gut microbiota and obesity and its related disorders, zebrafish was used as an animal model since its composition of the microbiota is similar to mammals, in addition to other beneficial features of this animal (13). Heart regeneration in zebrafish. Histological analysis revealed that dividing insulin positive cells are seen in both islets and pancreatic ducts, indicating that they might be a source of cell progenitors. J Cardiovasc Dev Dis. Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of therapeutic regeneration in the final 1-year results of the CADUCEUS trial (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). Additionally, a novel method for inducing liver injury is nitroreductase (NTR)- mediated hepatocyte ablation, exhibiting the differentiation of biliary epithelial cells (BECs) to mature hepatocytes (65). Although there are definitive benefits in using these models, their application is accompanied by some drawbacks. doi: 10.1096/fj.06-7503com, 96. Germ-free zebrafish and adult zebrafish fed with different amounts of lipid are some examples of models studied and resulted in new possibilities for treating obesity and its associated metabolic disorders by manipulation of intestinal microbiota (13, 92). Barrenho E, Miraldo M, Smith PC. Prince VE, Anderson RM, Dalgin G. Zebrafish pancreas development and regeneration: fishing for diabetes therapies. In spite of considerable progress in the personalized regenerative medicine field, there are still several uncertainties that need to be determined. Hence, to put these peculiar mechanisms away from the human ethical troubles, regeneration prone animal models should be identified. In this concept, endocrine disorders can be considered as potential candidates for regenerative medicine application. In fact, it can be due to increased complexity of tissues and metabolism in mammals because of the dependence of mammal regeneration responses on age and tissue changes. (2003) 263:6780. Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, et al. Additionally, zebrafish is used as an animal model in personalized medicine for studying different diseases like cancers as avatars due to its beneficial advantages which are discussed in this review (11, 12). doi: 10.1007/s00018-012-1037-y, 86. Additionally, changes in intestinal microbiota which include overproduction and release of bacterial endotoxins [lipopolysaccharides (LPS)] and increased small intestine permeability can cause liver damage which was studied in zebrafish. Ezetimibe and Simvastatin helped reduce cholesterol levels in zebrafish in one study which can mean cholesterol regulation pathways of humans and zebrafish closely resemble (80). Mechanical vessel injury in zebrafish embryos. (2012) 15:88594. Therefore, it can be said that the emerging field of zebrafish can be used for therapeutic approaches (61). Gut P, Reischauer S, Stainier DYR, Arnaout R. Little fish, big data: zebrafish as a model for cardiovascular and metabolic disease. EBioMedicine. In this review, we discuss the features of zebrafish that make it a desirable animal model, the advantages of zebrafish and recent research that shows zebrafish is a promising animal model for personalized regenerative diseases. From simple microorganisms to highly developed vertebrates are ranged in this category. Ruvinov E, Leor J, Cohen S. The promotion of myocardial repair by the sequential delivery of IGF-1 and HGF from an injectable alginate biomaterial in a model of acute myocardial infarction. doi: 10.1016/B978-0-12-386930-2.00005-7, 59. This animal has a remarkable capacity of organ regeneration including fins, CNS, heart, pancreas, liver and kidney, some of which are introduced (61). (2009) 58:184451. (2018) 2:122. Zebrafish as a model for drug screening in genetic kidney diseases. Ezetimibe and simvastatin reduce cholesterol levels in zebrafish larvae fed a high-cholesterol diet. Engel FB, Hsieh PC, Lee RT, Keating MT. Another mutation in cytochrome p450 family2 subfamily R member1 (cyp2r1) gene which makes the deficiency of 1,25(OH)2D3 (the active form of vitamin D), increases adiposity and causes growth retardation (9). (2018) 32:31728. Arnaout R, Ferrer T, Huisken J, Spitzer K, Stainier DYR, Tristani-Firouzi M, et al. Nat Med. Nowadays, Zebrafish (Danio rerio) as an emerging model draws attention to its unexceptional characteristics. Physiol Rev. FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring, and rescues function after myocardial infarction. (2019) 453:11129. Intraperitoneal injection of streptozotocin (STZ), a common way of chemical-induced diabetes in rodents, can effectively ablate cells, although higher concentration is needed (9, 93). (2005) 22:35970. A model of a zebrafish avatar for co-clinical trials. Hence, understanding the mechanisms of regeneration and endogenous tissue repair is of great importance in the prospects of regenerative medicine (67). In this method, the patient's cancer cells are xenotransplanted into avatars for determining drug efficacy. Indeed, animal models help us to build knowledge and develop personalized treatments, especially for chronic diseases and cancers. Studies have also revealed that sympathomimetic and parasympathomimetic agents produce similar results in both human and zebrafish (82). Hereupon, the preclinical study is a fundamental step. On the other hand, zebrafish is distinctly useful in personalized medicine when treatment options are abundant, etiologies are not well-established, or the abnormality is rare; like endocrine disorders, cancers, and Duchene muscular dystrophy (11, 74, 75). (2011) 471:230. doi: 10.1038/nature09855, 18. Use of large animal models to investigate Huntington's diseases. Hence, this ability provides a platform for in vivo examination of the regenerating cells to discover the related signals and pathways for reestablishing cell function and glucose homeostasis (63, 64). Front Cell Dev Biol. In this context, standard preclinical researches, as a fundamental step, should be implemented to properly investigate different procedures in order to reach a more applicable protocol translation to clinical settings. doi: 10.4155/fso.15.63, 44. (6, 3539). Goodarzi P, Aghayan HR, Larijani B, Soleimani M, Dehpour AR, Sahebjam M, et al. Since tests and researches in humans have been banned and can raise a lot of ethical problems, animals are ideal alternatives that provide a possibility for scientists to do different studies (6). Animal models are essential to biological research: issues and perspectives. It should be noted that due to the substantial capacity of cell regeneration in zebrafish, the cell mass restores after removing the ablation mechanism (9). Weger BD, Weger M, Nusser M, Brenner-Weiss G, Dickmeis T. A chemical screening system for glucocorticoid stress hormone signaling in an intact vertebrate. (2019) 20:1739. doi: 10.3390/ijms20071739, 78. Ultimately, zebrafish will be a powerful model for implementing personalized cell-based treatments, since the advantages of using zebrafish as a humanized disease model to investigate disease mechanisms and drug efficacy can help us overcome the drawbacks of using mice models, the interest in the former is growing rapidly (69). Zebrafish neural cells are also similar to human's microglia, astrocytes, motor neurons, etc. Sci Rep. (2020) 10:72. doi: 10.1038/s41598-019-56995-7, 113. There are specific traits of zebrafish that make it a suitable model for studies (49): Due to its simple natural habitat and size, zebrafish can be housed efficiently with up to 40 fish in a tank with the size of a standard mouse cage. (2020) 240:124970. doi: 10.1016/j.chemosphere.2019.124970, 112. 1. Med J Islamic Republ Iran. (2019) 12:12. doi: 10.3390/v12010012, Keywords: animal models, endocrine disease, personalized medicine, regeneration, zebrafish, Citation: Arjmand B, Tayanloo-Beik A, Foroughi Heravani N, Alaei S, Payab M, Alavi-Moghadam S, Goodarzi P, Gholami M and Larijani B (2020) Zebrafish for Personalized Regenerative Medicine; A More Predictive Humanized Model of Endocrine Disease. (2007) 21:20429. Today, diabetes mellitus (DM), obesity, and fatty liver disease are considered as leading concerns in public health (1, 2). doi: 10.1053/j.ackd.2017.10.011, PubMed Abstract | CrossRef Full Text | Google Scholar, 2. (1995) 203:253310. MP conducted search strategy and data collection. Ellis C, Ramzy A, Kieffer TJ. (2016) 134:97138. For example, difficulty in the evaluation of engraftment in the early steps, the adverse effects of irradiation regimes, prolonged engraftment assessing procedures, special maintenance requirements for immunosuppressed animals, and restriction in the number of animals that can be screened which consequently raise the overall cost and duration. Based on these studies, there are two major components of heart regeneration: proliferation of existing cardiomyocytes and an environment for stimulating muscle generation. Hence, an international rising effort is made to effectively cure these disorders or, at least, diminish their different side effects. Morrison MA, Zimmerman MW, Look AT, Stewart RA. Unlike several animal models, zebrafish has regeneration capability in its organs such as fins, central nervous system (CNS), heart, pancreas, liver, and kidney. Fishing for cures: the alLURE of using zebrafish to develop precision oncology therapies. (2016) 5:82635. They are immunocompromised small mammals, transplanted with human cells, tissues, and organs. Obesity researchers can also use zebrafish as a qualified animal model since adipose tissue development is based on the same principals in both species, studies also suggest similar genetic factors (83). Simoni E, Orsini G, Chicca M, Bettini S, Franceschini V, Martini A, et al. Using zebrafish contributed to a better understanding of related mechanisms and detection of EDCs (77). (2018) 47:26780. Eventually, there are some challenges in performing specific procedures such as intraperitoneal injections in zebrafish that are easily achievable in other animal models like mice (62). doi: 10.1016/j.jcyt.2017.04.008, 38. The chemical substances that interfere with the components of the endocrine system are called endocrine-disrupting components (EDCs). doi: 10.1016/bs.ctdb.2016.10.005, 94. In order to direct retinal development, Muller glia are induced to yield multipotent neuronal progenitor cells which migrate to the damaged site and differentiate in to the target cell type. Dev Dyn. The models are generated by different approaches including diet, genetic manipulation, surgery, and chemical induced destruction of cells in pancreas, some examples of which are shown in this figure. Since these disorders are complex conditions including genetic and environmental factors and they have no definite treatment, regenerative medicine (especially personalized regenerative medicine) has been investigated to find new therapies (3). In addition, due to its various potential benefits like regenerative capacity and its application in other areas of personalized medicine, it can be suggested as a personalized tool in this field (9, 63, 66). doi: 10.1097/00006676-200410000-00017, 110. Regenerative medicine approaches for age-related muscle loss and sarcopenia: a mini-review. Curr Top Dev Biol. (2007) 104:1131621. Proc Natl Acad Sci USA. New York, NY: Daedalus (1969). Studying the peripheral sympathetic nervous system and neuroblastoma in zebrafish. Additionally, in drug discovery studies expensive agents are used in smaller amounts resulting in a decrease in the overall budget. I. -like cells derived from human pluripotent stem cells. NPJ Precis Oncol. Development and validation of Alzheimer's disease animal model for the purpose of regenerative medicine. For developing insulin resistant transgenic models, one way is to express a dominant-negative IGF-I receptor (IGF-IR) in skeletal muscle, causing increased fasting blood glucose [Transgenic line (Tg) (acta1:dnIGF1R-EGFP)]. Another reason for zebrafish's convenience as a cardiovascular model is the imaging methods and physiological assays that have been developed to better study zebrafish cardiovascular system (59). Curr Drug Metab. Zebrafish have a large clutch size of 200300 per fish, which makes parallel hypotheses testing and rare genetic incident studies rather easier. Gen Comp Endocrinol. Pott A, Just S. Metabolic profiling of glucocorticoid deficiency: a fishing expedition. Patients with AHCY deficiency- a rare genetic disorder-not only have liver dysfunction but also some impairments in brain function, therefore, this model can be helpful to identify new therapeutic options for the patients (62, 78, 85). For instance, in order to study the complex system of the brain, vertebrates like Rat, Mouse, Zebrafish, Primates, with a highly developed nervous system and human resemblance are better choices. 5. Hinkle RT, Donnelly E, Cody DB, Bauer MB, Isfort RJ. Matthews RP, Lorent K, Maoral-Mobias R, Huang Y, Gong W, Murray IVJ, et al. The most common registered trials in the field of regenerative medicine are focused on cardiovascular diseases, nervous system diseases and musculoskeletal conditions (34). (2019) 12:dmm036004. Advances in the study of heart development and disease using zebrafish. Its small size, low cost of use, short generation time, need for small space, rapid reproduction, wide progeny, high homology with the human genome and physiology, and easy manipulation make it a suitable choice for different fields of biomedicine (47, 48). Hence, this study opened a new window in investigating potential therapeutic approaches for cell dysfunction and its associated disorders (94). The axonal regeneration is based on radial glial cells that infiltrate the lesion site and proliferate, which is affected by fibroblast growth factor (FGF) signaling. Accordingly, zebrafish is considered as an informative animal model for regenerative medicine due to its beneficial features including highly regenerative capacity and amenability to genetic manipulation, which makes it a therapeutic model for organ development and diseases, despite its limitations such as gene duplications (61, 66, 68). Michel M, Page-McCaw PS, Chen W, Cone RD. (2014) 60:158192. (2016) 55:7468. doi: 10.1161/CIRCGENETICS.114.000702, 55. Stages of embryonic development of the zebrafish. Research suggests similarities between human and zebrafish in peripheral nervous system development (81). (2012) 2012:564705. doi: 10.1155/2012/564705, 81. Mol Cell Endocrinol. (2018) 5:40. doi: 10.21037/sci.2018.11.01, 36. (2012) 47:164. doi: 10.1038/bmt.2011.81, 108. Although its size is an advantage in many procedures it can mean inadequate sample for a number of analysis. (2007) 134:28719. (2015) 96:e52460. As the most prevalent disease, cardiovascular diseases are known as the major causes of morbidity and mortality in many countries all over the world. Among the mentioned animal models, mouse models are mammals broadly used in biomedical researches which can be caused astonishing progress in this field. doi: 10.1007/s00438-020-01681-x, 114. It should be mentioned that not all of these approaches are appropriate for three main stages of zebrafish lifecycle (embryo, larva, and adult), although there might be some similarities. The significance of microbiome in personalized medicine. but most frequently used are mouse models (7, 8). Moreover, it is mentioned that zebrafish was used in investigating one of the unique features in humans, the gut microbiota, in order to find the associations between metabolic disorders and intestinal microbiota (13). It has now become clear that Zebrafish has many advantages over mice. Zang L, Maddison LA, Chen W. Zebrafish as a model for obesity and diabetes. Shiba Y, Fernandes S, Zhu W-Z, Filice D, Muskheli V, Kim J, et al. Curr Opin Oncol. On the contrarily, pancreas in adult zebrafish can recover after chemical treatment or surgery (pancreatectomy) without the help of insulin therapy. Hence, the development of these novel technologies could lead to astonishing advances in biomedicine. Borena BM, Martens A, Broeckx SY, Meyer E, Chiers K, Duchateau L, et al. Human pluripotent stem cell-derived atrial and ventricular cardiomyocytes develop from distinct mesoderm populations. Lee JH, Protze SI, Laksman Z, Backx PH, Keller GM. Animal modeling leads to extend science boundaries and astonishing improvements in clinical findings.
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