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Silva-Pedrosa, R.; Salgado, A.J.; Ferreira, P.E. The Emergence of Organoids in Cellular Systems. Encyclopedia. Available online: https://encyclopedia.pub/entry/44791 (accessed on 24 December 2024).
Silva-Pedrosa R, Salgado AJ, Ferreira PE. The Emergence of Organoids in Cellular Systems. Encyclopedia. Available at: https://encyclopedia.pub/entry/44791. Accessed December 24, 2024.
Silva-Pedrosa, Rita, António José Salgado, Pedro Eduardo Ferreira. "The Emergence of Organoids in Cellular Systems" Encyclopedia, https://encyclopedia.pub/entry/44791 (accessed December 24, 2024).
Silva-Pedrosa, R., Salgado, A.J., & Ferreira, P.E. (2023, May 24). The Emergence of Organoids in Cellular Systems. In Encyclopedia. https://encyclopedia.pub/entry/44791
Silva-Pedrosa, Rita, et al. "The Emergence of Organoids in Cellular Systems." Encyclopedia. Web. 24 May, 2023.
The Emergence of Organoids in Cellular Systems
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This entry is adapted from the peer-reviewed paper 10.3390/cells12060930

Cellular models have created opportunities to explore the characteristics of human diseases through well-established protocols, while avoiding the ethical restrictions associated with post-mortem studies and the costs associated with researching animal models. Organoids are 3D cellular structures that mimic the architecture and function of native tissues. They are generated in vitro from stem cells or differentiated cells, such as epithelial or neural cells, and are used to study organ development, disease modeling, and drug discovery. Organoids have become a powerful tool for understanding the cellular and molecular mechanisms underlying human physiology, providing new insights into the pathogenesis of cancer, metabolic diseases, and brain disorders. 

cell culture iPSCs disease modeling organoids 3D 2D cellular systems

1. Introduction

Cellular disease modeling is a powerful tool used to study the underlying mechanisms of various diseases and to develop new treatments. These models can be used to study both genetic and acquired diseases, including cancer, neurodegeneration, and infectious diseases [1][2][3][4].
One of the key benefits of cellular disease modeling is that it allows the study of diseases in a controlled environment in ways that would not be possible in a living organism, such as introducing specific genetic mutations or environmental factors to study their effects on the cells. Additionally, cellular disease modeling can also be used to study complex infectious diseases that involve multiple pathways and interactions between different cell types. By studying the effects of different viruses or bacteria on the cells, it is possible uncover the underlying mechanisms of the disease and to test the effectiveness of new treatments, providing insights into the disease process [5][6][7].
The ability to obtain an embryonic-like pluripotent state from differentiated murine fibroblasts using transcription factors changed the paradigm of the stem cell biology field [8]. One of the most commonly used models for studying cellular diseases involves the use of induced pluripotent stem cells (iPSCs). Human iPSCs can be obtained from different somatic tissue cell types and can be differentiated into any specialized cell type in the human body through specific factors that control cell fate [9][10]. Additionally, iPSCs can also be used to study genetic diseases, particularly those with unfathomable genetic backgrounds, which can provide insights into the underlying mechanisms of the disease [11] or when the translation of animal models is limited [12][13][14][15][16]. Furthermore, they can serve as a relevant model for studying host species and genotype-specific parasite interactions [17][18][19][20].
Organoids technology can recapitulate the complex cellular interactions and microenvironment of native tissues, enabling the study of disease-specific mechanisms in a more physiologically relevant context than traditional 2D cell culture or animal models. For instance, organoids derived from intestinal stem cells can be used to investigate inflammatory bowel disease, while those derived from neural stem cells can be used to study neurodegenerative disorders. Furthermore, organoids can be utilized to study the effects of genetic variations or environmental factors on organ development and function, providing insights into the mechanisms that underlie human diseases [21][22][23].

2. iPSCs

The discovery of iPSCs from mouse ESC was first reported in 2006 by a team of scientists led by Shinya Yamanaka. They demonstrated that by introducing four specific transcription factors, octamer-binding transcription factor 3 or 4 (Oct3/4), sex-determining region Y-box 2 (SOX2), myc pronto-oncogene (c-Myc), and Kruppel-like factor 4 (Klf4), through retrovirus-mediated transfection, they could reprogram adult cells into a pluripotent state. In 2007, the same team generated and cultured iPSCs from adult human fibroblasts using the same retroviral transduction factors, which exhibited similar characteristics and differentiation potential in vitro and teratomas to hESC [9]. Regarding the reprogramming process, iPSCs exhibit similar results in morphology, proliferation, gene expression, and teratomas compared to embryonic stem cells, avoiding the ethical concerns related with the use of embryonic stem cells [8][24][25][26]. This breakthrough was a significant step forward in the field of stem cell research, as it provided a way to generate patient-specific pluripotent cells without the need for embryos, which had been a major ethical concern in the field [26][27].
Since the discovery of iPSCs, there have been many advancements in the technology used to generate and manipulate these cells. The use of viral vectors to introduce the reprogramming factors was replaced by non-viral methods, such as the use of plasmids or proteins, which eliminated the risk of insertional mutagenesis. Additionally, the number of reprogramming factors required were reduced, making the process more efficient and cost-effective [28][29]. Some of the advantages of using iPSCs include:
  • Ethical concerns: iPSCs can be derived from adult cells, avoiding the ethical concerns associated with embryonic stem cell research [30];
  • Patient-specific cells: iPSCs can be generated from a patient’s own cells, allowing for the creation of patient-specific cells for use in therapy. This can help to avoid immune rejection of the transplanted cells [31];
  • Disease modeling: iPSCs can be used to create models of specific diseases, which can aid in the understanding of the disease and the development of new treatments [18];
  • Drug development: iPSCs can be used to test the safety and efficacy of new drugs on a variety of cell types, including those that are difficult to obtain from living donors [32][33];
  • Tissue repair and regeneration: iPSCs have the potential to be used to repair or regenerate damaged or diseased tissue, such as in the treatment of heart disease, diabetes, and neurodegenerative disorders [15];
  • Cost-effective: iPSCs can be created from a small sample of adult cells; however, can be very cost-effective compare to other methods [34][35][36].
The potential applications of iPSCs are vast, and ongoing research is being conducted in several areas. One of the most promising fields is regenerative medicine, where iPSCs can be used to generate specific cell types for tissue engineering and cell replacement therapy. For example, iPSCs can be differentiated into heart muscle cells, which can then be used to repair damaged heart tissue in patients with heart disease [37][38][39]. Similarly, iPSCs can be differentiated into insulin-producing cells, which can be used to treat patients with diabetes [40][41].
iPSCs differentiated into hepatocyte-like cells can be a good substitute for primary human hepatocytes because they can be maintained in long-term culture. Moreover, generating cells from patients with specific genetic backgrounds to study genotype-phenotype relationships may in the future avoid the need for organ donation [42][43].
Proof-of-concept studies revealed the efficacy of these cells in drug development, high-throughput drug screening, and modeling liver diseases and viral and parasitic infections, such as malaria [44][45].
Another area of research for iPSCs is drug discovery and development. Through the generation of iPSCs from patients with specific diseases, in vitro models of these diseases can be created and used to study the underlying causes of the disease and to test the efficacy of new drugs. This can greatly accelerate the drug development process and ultimately lead to new treatments for patients [46][47].
iPSCs also have potential applications in personalized medicine, with iPSCs generated from a patient’s own cells; researchers can create patient-specific cells that can be used in cell-based therapies. Additionally, iPSCs can be used to generate patient-specific organoids, which are miniaturized versions of organs that can be used to study the development and progression of diseases [48][49] (Figure 1).
Figure 1. Culture of human-induced pluripotent stem cells in the 2D culture system and differentiation into 3D organoids. Somatic cells are isolated from a human patient, cultured in vitro, and transduced by pluripotency transcription factors, such as OCT-4, SOX-2, KLF-4, and c-MYC. Through reprogramming that induces a pluripotent state in somatic cells, induced pluripotent stem cells (iPSCs) are generated. Cells are cultured and differentiated under specific factors and matrices to generate organoids. Created with BioRender.com, accessed on 23 July 2022.
iPSCs technology was extensively studied for neurological disorders in recent years due to the limitations of studying the human brain. iPSCs can be directly generated from patients with neurological diseases, allowing the study of nervous system diseases in vitro using 2D, 3D, and BBB models [50][51][52][53]. The iPSCs differentiation and their use as in vitro model of neurodegenerative disorders, such as Parkinson’s disease (PD), enables a better understanding of neuronal cell death and contributes to the development of drug discovery [47][54]. iPSC derived from PD and differentiated into dopaminergic neurons revealed disease-related cell phenotypes, such as impaired mitochondrial function, increased oxidative stress, increased apoptosis, and an accumulation of α-synuclein, providing more insights into PD pathophysiology [51][55].
The iPSC lines derived from Alzheimer’s disease (AD) patients, a neurodegenerative disease characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles with progressive cognitive decline, showed neurons differentiated with disease characteristics. A study demonstrated an increased Aβ42:40 percentage of generated cortical neurons from AD patients-iPSC lines compared with control neurons of non-AD iPSCs and different signatures for Aβ43, Aβ38, Aβ fragments in 2D and 3D cultures [56]. Hence, iPSCs from patient-derived neural cells can reflect the human genetics and physiology of AD and other dementia diseases, being an excellent cellular model to explore Alzheimer’s pathogenesis and lead to neuronal drug discovery [57][58].
However, there are also some ethical concerns surrounding the use of iPSCs. One concern is that the use of iPSCs in research and therapy could perpetuate inequalities in access to healthcare, as the technology to generate and manipulate these cells is currently expensive and not widely available [59]. Moreover, there are concerns about the limitation of genetic diversity, which jeopardizes equity and can impede the acceleration of biological discoveries [60]. There is also potential for the use of iPSCs in controversial areas, such as human cloning or the creation of genetically modified organisms [61][62].
The iPSCs technology also has several technical and scientific drawbacks that must be overcome for its full potential to be realized. One major technical weakness of iPSC technology is the variability in the quality and characteristics of iPSCs generated from different sources. iPSCs can vary in their differentiation potential, genomic stability, epigenetic modifications, and gene expression patterns. These variations can be influenced by the methods of reprogramming, the quality of the starting cells, and the culture conditions used to maintain the iPSCs. This variability can make it difficult to compare results between studies and to predict the behavior of iPSC-derived cells in a clinical setting [63][64][65][66].
The efficiency of the iPSCs reprogramming process can be low, especially for certain cell types or patient populations. Additionally, the reprogramming process can be time-consuming and expensive, requiring the use of multiple factors and genetic modifications. Scientifically, one of the major drawbacks of iPSC technology is the potential for genetic abnormalities to be introduced during the reprogramming process. Reprogramming can lead to changes in gene expression, DNA methylation patterns, and chromosomal stability, which can alter the properties and behavior of iPSCs and their differentiated derivatives. These changes can also increase the risk of tumor formation or other adverse effects when iPSC-derived cells are used in a clinical context [67][68][69].
Furthermore, iPSC technology faces challenges in differentiating into specific cell types with high efficiency and fidelity. The protocols for differentiation can be complex and require optimization for each cell type, and there can be significant variability in the quality and purity of the differentiated cells produced. Additionally, there may be functional differences between iPSC-derived cells and their natural counterparts, which may limit their therapeutic potential [70][71][72][73][74].
In conclusion, due to the plasticity of iPSCs in differentiation into several cell types and their self-renewal capacity, they constitute a vital tool for research in regenerative medicine, neurological disease modeling, cell therapies, and drug screening [12][47][54][57][75][76][77][78][79][80][81][82]. However, iPSC technology holds technical and scientific hurdles that must be overcome to fully realize its potential. Continued research and development in iPSC technology will be critical to address these challenges and to enable the safe and effective use of iPSC-derived cells in clinical applications, as well as to address the ethical concerns surrounding their use [30].

3. Cell Culture System—From 2D to 3D

Cell culture is the process of growing cells in a controlled environment outside of their natural setting; the two main types of cell culture systems are 2D and 3D [83].
The 2D cell culture system refers to the growth of cells on a flat surface, such as a Petri dish, microscope slide, or a culture plate. This is the most common and well-established type of cell culture, and it is widely used in basic research, drug discovery, and biotechnology [84]. In a 2D cell culture system, cells are grown in monolayers and are typically maintained in a liquid medium, such as nutrient broth or serum-containing medium, which provides the necessary nutrients and growth factors for cell growth and proliferation [84][85][86][87].
An important application of 2D culture is the production of biological products. Many of these products, such as monoclonal antibodies and recombinant proteins, are produced through cells that were grown in 2D culture. These cells can be genetically engineered to produce specific proteins, which are then harvested and purified to create the final product [88][89].
The usage of iPSCs in 2D culture can help better understand neurotransmission, the central nervous system, and the differentiation of neurons, astrocytes, and microglia [90], giving more insights into the genetic and molecular conditions of neurological disorders [76].
Advantages of 2D cell culture include its simplicity and ease of use, as well as its accessibility and low cost, due to the easy set up and maintenance, the cells can be easily observed and manipulated. Additionally, 2D cell culture is well-suited for growing a wide range of cell types, including primary cells, stem cells, and cancer cells and allows the differentiation of specific subtypes of cells in a dish [91][92][93].
Although 2D cell culture is widely used and valuable tool in laboratory research, it has a limited role in the disease modeling because it cannot accurately resemble the dynamic complexity of the in vivo environment, cell–cell communications, and tissue- and organ-level structures. This is because 2D cultures can only do so for differentiation of one cell type in a mono-culture system [76][90][94][95][96][97], leading to artificial behavior of cells, such as altered proliferation and differentiation, and reduced cellular interaction compared to in vivo conditions [98][99]. For example, drug development has a high-cost when the process goes from target identification stage to clinical use. The drug screening performed in cells cultured in 2D is not representative of cells in a tissue microenvironment, resulting in a high failure rate in drug discovery and low levels of approved drugs in the market [100].
Despite these limitations, 2D cell culture remains a valuable tool in the laboratory, and recent advances improved the system, such as techniques for analyzing and characterizing cells, such as high-content imaging and transcriptomics.
The use of 3D cell culture systems started more than a decade ago and allow more complexity between cells’ interaction with heterotypic settings, mimicking multiple structures, using scaffold-based or scaffold-free cultures [76][101]. This system present similarities with tissue architecture in vivo, respecting the phenotypic and functional characteristics and circumventing a limitation of monolayer cultures [102][103].
Despite these limitations, 2D cell culture remains a valuable tool in the laboratory, and many advances were made in recent years to improve the system, such as techniques for analyzing and characterizing cells, such as high-content imaging and transcriptomics. These techniques allow for a more detailed understanding of the behavior and characteristics of cells in culture [104][105].
Scaffolds-based techniques are typically made of synthetic or natural materials, such as hydrogel-based supports, which provide a physical structure for cells to attach and grow on. Scaffold-free technique can be used to create small structures, such as microchannels and microwells, that can control cell behavior, such as suspended microplates or spheroids with coated ultra-low attachment microplates. Hydrogels are hydrophilic polymeric materials that can mimic the extracellular matrix (ECM), such as fibrinogen, hyaluronic acid, collagen, matrigel, or gelatin, providing a supportive environment for cells. They allow soluble factors such as cytokines and growth factors to move through the tissue-like gel [87][100].
The 3D cell culture system also allows for the study of cell–cell interactions, cell-matrix interactions, and cell-microenvironment interactions that closely mimics the in vivo microenvironment [51][106]. Moreover, 3D cell culture enables the formation of complex cellular structures, such as spheroids involved in bone regeneration [107] and organoids. These features provide insights about the organ’s behavior and bridge the gap between 2D cell culture and animal models [87].
Organoids and spheroids are 3D structures that are increasingly used in biological and medical research, as they better mimic the in vivo environment compared to traditional 2D cell cultures. Although organoids and spheroids have some similarities, they have distinct differences that distinguish them from one another [108].
Organoids are 3D structures derived from stem cells or tissue explants that can self-organize into structures resembling specific organs. They exhibit complex cellular organization, spatial orientation, and function similar to that of the in vivo tissue, composed of multiple cell types, and can be used to study organ development, disease modeling, and drug screening. They are typically cultured in a specialized medium containing growth factors that promote differentiation and tissue-specific gene expression [108][109][110][111]. Spheroids, on the other hand, are aggregates of cells that form a 3D structure, but lack the complex organization and functional specialization of organoids, and often have a homogenous cell population. They can be generated by culturing cells in non-adherent conditions, such as suspension cultures, hanging drops, or microfluidic devices. Spheroids can be composed of a single cell type or multiple cell types and can be used to study cell–cell interactions, drug screening, and tumor biology [112][113][114][115].
Other 3D structures that can be generated in vitro include organotypic cultures, tissue-engineered constructs, and scaffolds. Organotypic cultures are 3D cultures that resemble the in vivo tissue architecture but lack the self-organization seen in organoids. Tissue-engineered constructs are artificial structures that are created using cells and biomaterials and can be used for tissue engineering applications. Scaffolds are 3D structures that provide support for cells to grow and differentiate, and can be used for tissue engineering, drug screening, and regenerative medicine applications [116][117][118][119][120]. In summary, while organoids, spheroids, and other 3D structures have some similarities, they can be distinguished by their cellular organization, complexity, and functional specialization. Organoids are self-organized structures that resemble specific organs, while spheroids are simple aggregates of cells lacking distinct organization. Other 3D structures, such as organotypic cultures, tissue-engineered constructs, and scaffolds, are useful for a range of applications, including tissue engineering and drug screening.
Additionally, the 3D cell culture has the potential to provide different cell types, giving helpful information about tumor cell biology, signal transduction, cell migration, drug discovery, angiogenesis, metabolic profiling, inflammation, and apoptosis. Moreover, the 3D culture model exhibits cellular behavior that is more similar to in vivo in responses to oxidative stress compared to the 2D model [121]. For example, the 3D culture allowed us to understand how the formative components of the cerebellar structure interact and how they self-organize and differentiate into Purkinje cells. The addition of the factors lead to a polarized design with a rhombic-lip-like layout and a three-layered cytoarchitecture similar to the human embryonic cerebellum, as in the first trimester [122]. The 3D model applied in neural cell culture of AD pathogenesis study showed relevant information about amyloid-β (Aβ) aggregation and increased concentration of hyperphosphorylated tau [123][124].
The 3D model could be used for pre-clinical studies at a low cost, such as for the gastrointestinal tract–liver system [125]. It is a potential new model for pre-clinical stage research, providing relevant information about other types of diseases, and could contribute to the use of fewer animal models [87][125][126]. Moreover, it is a model that can be used to study drug efficacy and toxicity because it can provide a more realistic model for drug testing, allowing for a better understanding of how drugs interact with cells. However, there are also some limitations associated with 3D cell culture, such as the complexity of the system and the difficulty of monitoring the cells within it. With the growing interest in 3D cell culture, it is expected that this field will continue to develop and provide new opportunities for research and drug development in the future [87][100].
In conclusion, 2D and 3D cell culture systems are both important tools in cell biology research and biotechnology, but they have distinct advantages and limitations. The 2D cell culture system is well-established, simple, and accessible, while 3D cell culture more closely mimics the in vivo environment of cells, making it useful for studying certain types of biological processes. Both 2D and 3D cell culture are important for understanding the biology of cells and for developing new therapies [99][127].

4. Organoids Technology

Organoids are 3D structures, miniaturized versions of organs that are grown in a lab using stem cells or other cell types. These structures closely mimic the architecture, function, and behavior of their in vivo counterparts, making them valuable tools for studying a wide range of biological processes and diseases [111][128].
Organoids can form endodermal, mesodermal, and ectodermal organs. Organs derived from cells of the endoderm layer are usually associated with complex systems, including the gastrointestinal and respiratory tract, and all their associated organs. Mesoderm derivatives are associated with blood vessels, muscles, kidneys, heart, bone, cartilage, and reproductive organs. Those derived from the ectoderm, from the cells of the epithelium layers, are related to the nervous system, such as the brain [22]. Additionally, organoids can be established in different ways, through the extracellular matrix, such as collagen or matrigel, and with differentiating factors, in plates, or rotating bioreactors, which are usually used for cerebral organoids as they allow greater medium perfusion. Air-liquid interface (ALI) can also generate organoids, such as microfluidic, in which the top layer of cells is exposed to air, and the basal layer is in contact with the culture medium, usually applied to renal, gastrointestinal, and neural organoids [22][129][130][131].
Organoids have gained particular focus as an appealing model since they are 3D self-organized structures and the microenvironment is preserved, including morphological and biological issues of organs. They can mimic genetic diseases, host-infectious disease interaction, regenerative therapy, or drug screening using patient-specific iPSCs cells and establishing biobanks. Furthermore, through molecular technologies, such as the lentiviral expression system and CRISPR/CAS9, it is possible to manipulate the genome of organoids, allowing for disease replication and targeted gene therapy [23][76][132][133].
Organoids can be used to study human biology and disease in a way that is not possible with traditional cell culture or animal models. For example, organoids can be derived from patient-specific stem cells, allowing researchers to study the effects of genetic mutations on organ development and function in a way that is not feasible in vivo. Organoids have been used to study a wide range of organs and systems, including the brain, liver, pancreas, and gut. For instance, brain organoids were used to study the development of neural circuits and the effects of genetic mutations on brain function [134][135][136][137].
Organoids are a potential tool to study organ transplantation and the process of transplant rejection, as well as to test new drugs and other treatments that could be used to prevent rejection. Understanding genetic mutations associated with organ-specific diseases, as well as how genetic mutations affect organ development and function, are important factors that can be explored [138][139][140].
Organoids are a powerful tool for studying human biology and disease, as they allow for the study of the effects of genetic mutations and environmental factors on organ development and function, which is not possible with traditional cell culture or animal models. In addition, organoids can be used to study the efficacy and toxicity of different drug treatments, providing a more physiologically relevant context for drug screening or pathways, providing insights into the mechanisms of drug action. As the technology continues to improve, organoids are likely to play an increasingly important role in scientific research and the development of new treatments for a wide range of diseases. Moreover, organoids have the potential to revolutionize the way of study human diseases and develop new therapeutics, but further research is needed to fully realize their potential. With the continued growth of organoid technology, significant advances are expected in the fields of disease modeling, drug discovery, and personalized medicine [141] (Figure 2).
Figure 2. Organoid applications. Organoids have the potential for several purposes, such as basic research, drug screening, genomic and metabolomic analysis, and gene editing to explore disease-linked alleles, called genetic engineering. Moreover, organoids can model diseases, have applications in cell immunotherapy and regenerative medicine, and provide the opportunity to have biobanks. Created with BioRender.com, accessed on 23 July 2022.

References

  1. Tidball, A.M. Disease in a Dish: Cellular Models to Understand Human Conditions. In Cellular and Animal Models in Human Genomics Research; Academic Press: Cambridge, MA, USA, 2019; pp. 19–47.
  2. Penney, J.; Ralvenius, W.T.; Tsai, L.H. Modeling Alzheimer’s disease with iPSC-derived brain cells. Mol. Psychiatry 2019, 25, 148–167.
  3. Avior, Y.; Sagi, I.; Benvenisty, N. Pluripotent stem cells in disease modelling and drug discovery. Nat. Rev. Mol. Cell Biol. 2016, 17, 170–182.
  4. Lancaster, M.A.; Huch, M. Disease modelling in human organoids. Dis. Model. Mech. 2019, 12, dmm039347.
  5. Schlaermann, P.; Toelle, B.; Berger, H.; Schmidt, S.C.; Glanemann, M.; Ordemann, J.; Bartfeld, S.; Mollenkopf, H.J.; Meyer, T.F. A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro. Gut 2016, 65, 202–213.
  6. Heo, I.; Dutta, D.; Schaefer, D.A.; Iakobachvili, N.; Artegiani, B.; Sachs, N.; Boonekamp, K.E.; Bowden, G.; Hendrickx, A.P.A.; Willems, R.J.L.; et al. Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat. Microbiol. 2018, 3, 814–823.
  7. Qian, X.; Nguyen, H.N.; Song, M.M.; Hadiono, C.; Ogden, S.C.; Hammack, C.; Yao, B.; Hamersky, G.R.; Jacob, F.; Zhong, C.; et al. Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell 2016, 165, 1238–1254.
  8. Takahashi, K.; Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126, 663–676.
  9. Takahashi, K.; Tanabe, K.; Ohnuki, M.; Narita, M.; Ichisaka, T.; Tomoda, K.; Yamanaka, S. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell 2007, 131, 861–872.
  10. Nishikawa, S.-I.; Goldstein, R.A.; Nierras, C.R. The promise of human induced pluripotent stem cells for research and therapy. Nat. Rev. Mol. Cell Biol. 2008, 9, 725–729.
  11. Sürün, D.; Schneider, A.; Mircetic, J.; Neumann, K.; Lansing, F.; Paszkowski-Rogacz, M.; Hänchen, V.; Lee-Kirsch, M.A.; Buchholz, F. Efficient Generation and Correction of Mutations in Human iPS Cells Utilizing mRNAs of CRISPR Base Editors and Prime Editors. Genes 2020, 11, 511.
  12. Robinton, D.A.; Daley, G.Q. The promise of induced pluripotent stem cells in research and therapy. Nature 2012, 481, 295–305.
  13. Wen, Z.; Christian, K.M.; Song, H.; Ming, G.-L. Modeling psychiatric disorders with patient-derived iPSCs. Curr. Opin. Neurobiol. 2016, 36, 118–127.
  14. Brennand, K.; Simone, A.; Jou, J.; Gelboin-Burkhart, C.; Tran, N.; Sangar, S.; Li, Y.; Mu, Y.; Chen, G.; Yu, D.; et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011, 473, 221–225.
  15. Crook, J.M.; Tomaskovic-Crook, E. Bioprinting 3D Human Induced Pluripotent Stem Cell Constructs for Multilineage Tissue Engineering and Modeling. Methods Mol. Biol. 2020, 2140, 251–258.
  16. Csobonyeiova, M.; Polak, S.; Danisovic, L. Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy. Int. J. Mol. Sci. 2020, 21, 2239.
  17. Karagiannis, P.; Takahashi, K.; Saito, M.; Yoshida, Y.; Okita, K.; Watanabe, A.; Inoue, H.; Yamashita, J.K.; Todani, M.; Nakagawa, M.; et al. Induced Pluripotent Stem Cells and Their Use in Human Models of Disease and Development. Physiol. Rev. 2019, 99, 79–114.
  18. Rowe, R.G.; Daley, G.Q. Induced pluripotent stem cells in disease modelling and drug discovery. Nat. Rev. Genet. 2019, 20, 377–388.
  19. Cavalli, E.; Battaglia, G.; Basile, M.S.; Bruno, V.; Petralia, M.C.; Lombardo, S.D.; Pennisi, M.; Kalfin, R.; Tancheva, L.; Fagone, P.; et al. Exploratory Analysis of iPSCS-Derived Neuronal Cells as Predictors of Diagnosis and Treatment of Alzheimer Disease. Brain Sci. 2020, 10, 166.
  20. Klotz, C.; Aebischer, T.; Seeber, F. Stem cell-derived cell cultures and organoids for protozoan parasite propagation and studying host–parasite interaction. Int. J. Med. Microbiol. 2012, 302, 203–209.
  21. Wang, Z.; Wang, S.-N.; Xu, T.-Y.; Miao, Z.-W.; Su, D.-F.; Miao, C.-Y. Organoid technology for brain and therapeutics research. CNS Neurosci. Ther. 2017, 23, 771–778.
  22. Shariati, L.; Esmaeili, Y.; Javanmard, S.H.; Bidram, E.; Amini, A. Organoid technology: Current standing and future perspectives. Stem Cells 2021, 39, 1625–1649.
  23. Dutta, D.; Heo, I.; Clevers, H. Disease Modeling in Stem Cell-Derived 3D Organoid Systems. Trends Mol. Med. 2017, 23, 393–410.
  24. Thomson, J.A.; Itskovitz-Eldor, J.; Shapiro, S.S.; Waknitz, M.A.; Swiergiel, J.J.; Marshall, V.S.; Jones, J.M. Embryonic stem cell lines derived from human blastocysts. Science 1998, 282, 1145–1147.
  25. Lee, S.H.; Lee, H.S.; Moon, H.C.; Kim, D.H.; Park, Y.S.; Hwang, B.; Lee, H.Y. The Effect of α-pinene from Pinus densiflora S. and a Polysaccharide from Angelica gigas Nakai on Differentiation and Proliferation of Human Embryonic Stem Cells. Cytotechnology 2005, 49, 87–94.
  26. Volarevic, V.; Markovic, B.S.; Gazdic, M.; Volarevic, A.; Jovicic, N.; Arsenijevic, N.; Armstrong, L.; Djonov, V.; Lako, M.; Stojkovic, M. Ethical and Safety Issues of Stem Cell-Based Therapy. Int. J. Med Sci. 2018, 15, 36–45.
  27. Zacharias, D.G.; Nelson, T.J.; Mueller, P.S.; Hook, C.C. The Science and Ethics of Induced Pluripotency: What Will Become of Embryonic Stem Cells? Mayo Clin. Proc. 2011, 86, 634–640.
  28. Deng, X.-Y.; Wang, H.; Wang, T.; Fang, X.-T.; Zou, L.; Li, Z.-Y.; Liu, C.-B. Non-Viral Methods For Generating Integration-Free, Induced Pluripotent Stem Cells. Curr. Stem Cell Res. Ther. 2015, 10, 153–158.
  29. Trevisan, M.; Desole, G.; Costanzi, G.; Lavezzo, E.; Palù, G.; Barzon, L. Reprogramming Methods Do Not Affect Gene Expression Profile of Human Induced Pluripotent Stem Cells. Int. J. Mol. Sci. 2017, 18, 206.
  30. Moradi, S.; Mahdizadeh, H.; Šarić, T.; Kim, J.; Harati, J.; Shahsavarani, H.; Greber, B.; Moore, J.B., IV. Research and therapy with induced pluripotent stem cells (iPSCs): Social, legal, and ethical considerations. Stem Cell Res. Ther. 2019, 10, 341.
  31. Paik, D.T.; Chandy, M.; Wu, J.C. Patient and Disease–Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics. Pharmacol. Rev. 2019, 72, 320–342.
  32. Ovics, P.; Regev, D.; Baskin, P.; Davidor, M.; Shemer, Y.; Neeman, S.; Ben-Haim, Y.; Binah, O. Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening. Int. J. Mol. Sci. 2020, 21, 7320.
  33. Pasteuning-Vuhman, S.; de Jongh, R.; Timmers, A.; Pasterkamp, R.J. Towards Advanced iPSC-based Drug Development for Neurodegenerative Disease. Trends Mol. Med. 2021, 27, 263–279.
  34. Lyra-Leite, D.M.; Fonoudi, H.; Gharib, M.; Burridge, P.W. An updated protocol for the cost-effective and weekend-free culture of human induced pluripotent stem cells. STAR Protoc. 2021, 2, 100213.
  35. D’Antonio, M.; Woodruff, G.; Nathanson, J.L.; D’Antonio-Chronowska, A.; Arias, A.; Matsui, H.; Williams, R.; Herrera, C.; Reyna, S.M.; Yeo, G.W.; et al. High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells. Stem Cell Rep. 2017, 8, 1101–1111.
  36. Beers, J.; Linask, K.L.; Chen, J.A.; Siniscalchi, L.I.; Lin, Y.; Zheng, W.; Rao, M.; Chen, G. A cost-effective and efficient reprogramming platform for large-scale production of integration-free human induced pluripotent stem cells in chemically defined culture. Sci. Rep. 2015, 5, 11319.
  37. Csöbönyeiová, M.; Polák, Š.; Danišovič, L. Perspectives of induced pluripotent stem cells for cardiovascular system regeneration. Exp. Biol. Med. 2015, 240, 549–556.
  38. Rikhtegar, R.; Pezeshkian, M.; Dolati, S.; Safaie, N.; Rad, A.A.; Mahdipour, M.; Nouri, M.; Jodati, A.R.; Yousefi, M. Stem cells as therapy for heart disease: iPSCs, ESCs, CSCs, and skeletal myoblasts. Biomed. Pharmacother. 2019, 109, 304–313.
  39. Zhu, D.; Cheng, K. Cardiac Cell Therapy for Heart Repair: Should the Cells Be Left Out? Cells 2021, 10, 641.
  40. Walczak, M.P.; Drozd, A.M.; Stoczynska-Fidelus, E.; Rieske, P.; Grzela, D.P. Directed differentiation of human iPSC into insulin producing cells is improved by induced expression of PDX1 and NKX6.1 factors in IPC progenitors. J. Transl. Med. 2016, 14, 341.
  41. Silva, I.B.B.; Kimura, C.H.; Colantoni, V.P.; Sogayar, M.C. Stem cells differentiation into insulin-producing cells (IPCs): Recent advances and current challenges. Stem Cell Res. Ther. 2022, 13, 309.
  42. Poorna, M.; Sudhindran, S.; Thampi, M.; Mony, U. Differentiation of induced pluripotent stem cells to hepatocyte-like cells on cellulose nanofibril substrate. Colloids Surf. B Biointerfaces 2021, 198, 111466.
  43. Hu, C.; Li, L. In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration. Protein Cell 2015, 6, 562–574.
  44. Corbett, J.L.; Duncan, S.A. iPSC-Derived Hepatocytes as a Platform for Disease Modeling and Drug Discovery. Front. Med. 2019, 6, 265.
  45. Davidson, M.D.; Ware, B.R.; Khetani, S.R. Stem Cell-Derived Liver Cells for Drug Testing and Disease Modeling. Discov. Med. 2015, 19, 349–358.
  46. Nicholson, M.W.; Ting, C.Y.; Chan, D.Z.; Cheng, Y.C.; Lee, Y.C.; Hsu, C.C.; Huang, C.Y.; Hsieh, P.C. Utility of iPSC-Derived Cells for Disease Modeling, Drug Development, and Cell Therapy. Cells 2022, 11, 1853.
  47. Farkhondeh, A.; Li, R.; Gorshkov, K.; Chen, K.G.; Might, M.; Rodems, S.; Lo, D.C.; Zheng, W. Induced pluripotent stem cells for neural drug discovery. Drug Discov. Today 2019, 24, 992–999.
  48. Sharma, A.; McKeithan, W.L.; Serrano, R.; Kitani, T.; Burridge, P.W.; del Alamo, J.C.; Mercola, M.; Wu, J.C. Use of human induced pluripotent stem cell–derived cardiomyocytes to assess drug cardiotoxicity. Nat. Protoc. 2018, 13, 3018–3041.
  49. Ferreira, L.M.; Mostajo-Radji, M.A. How induced pluripotent stem cells are redefining personalized medicine. Gene 2013, 520, 1–6.
  50. Chandrasekaran, A.; Avci, H.X.; Ochalek, A.; Rösingh, L.N.; Molnár, K.; László, L.; Bellák, T.; Téglási, A.; Pesti, K.; Mike, A.; et al. Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells. Stem Cell Res. 2017, 25, 139–151.
  51. Liu, C.; Oikonomopoulos, A.; Sayed, N.; Wu, J.C. Modeling human diseases with induced pluripotent stem cells: From 2D to 3D and beyond. Development 2018, 145, dev156166.
  52. Bordoni, M.; Rey, F.; Fantini, V.; Pansarasa, O.; Di Giulio, A.M.; Carelli, S.; Cereda, C. From Neuronal Differentiation of iPSCs to 3D Neuro-Organoids: Modelling and Therapy of Neurodegenerative Diseases. Int. J. Mol. Sci. 2018, 19, 3972.
  53. Costamagna, G.; Andreoli, L.; Corti, S.; Faravelli, I. iPSCs-Based Neural 3D Systems: A Multidimensional Approach for Disease Modeling and Drug Discovery. Cells 2019, 8, 1438.
  54. Caiazza, M.C.; Lang, C.; Wade-Martins, R. What we can learn from iPSC-derived cellular models of Parkinson’s disease. Prog. Brain Res. 2020, 252, 3–25.
  55. Torrent, R.; Rigotti, F.D.A.; Dell’Era, P.; Memo, M.; Raya, A.; Consiglio, A. Using iPS Cells toward the Understanding of Parkinson’s Disease. J. Clin. Med. 2015, 4, 548–566.
  56. Arber, C.; Toombs, J.; Lovejoy, C.; Ryan, N.S.; Paterson, R.W.; Willumsen, N.; Gkanatsiou, E.; Portelius, E.; Blennow, K.; Heslegrave, A.; et al. Familial Alzheimer’s disease patient-derived neurons reveal distinct mutation-specific effects on amyloid beta. Mol. Psychiatry 2019, 25, 2919–2931.
  57. Machairaki, V. Human Pluripotent Stem Cells as In Vitro Models of Neurodegenerative Diseases. Adv. Exp. Med. Biol. 2020, 1195, 93–94.
  58. Tcw, J. Human iPSC application in Alzheimer’s disease and Tau-related neurodegenerative diseases. Neurosci. Lett. 2019, 699, 31–40.
  59. Ellison, B. Stem Cell Research and Social Justice: Aligning Scientific Progress with Social Need. Curr. Stem Cell Rep. 2016, 2, 328–335.
  60. Ghosh, S.; Nehme, R.; Barrett, L.E. Greater genetic diversity is needed in human pluripotent stem cell models. Nat. Commun. 2022, 13, 7301.
  61. Omole, A.E.; Fakoya, A.O.J.; Nnawuba, K.C.; Haider, K.H. Common Ethical Considerations of Human-Induced Pluripotent. In Handbook of Stem Cell Therapy; Singapore: Singapore, 2022; pp. 1–17.
  62. Ayala, F.J. Cloning humans? Biological, ethical, and social considerations. Proc. Natl. Acad. Sci. USA 2015, 112, 8879–8886.
  63. Chlebanowska, P.; Sułkowski, M.; Skrzypek, K.; Tejchman, A.; Muszyńska, A.; Noroozi, R.; Majka, M. Origin of the Induced Pluripotent Stem Cells Affects Their Differentiation into Dopaminergic Neurons. Int. J. Mol. Sci. 2020, 21, 5705.
  64. Carvalho, A.B.; Coutinho, K.C.D.S.; Barbosa, R.A.Q.; de Campos, D.B.P.; Leitão, I.D.C.; Pinto, R.S.; Dos Santos, D.S.; Farjun, B.; Araújo, D.d.S.d.; Mesquita, F.C.P.; et al. Action potential variability in human pluripotent stem cell-derived cardiomyocytes obtained from healthy donors. Front. Physiol. 2022, 13, 2667.
  65. Féraud, O.; Valogne, Y.; Melkus, M.W.; Zhang, Y.; Oudrhiri, N.; Haddad, R.; Daury, A.; Rocher, C.; Larbi, A.; Duquesnoy, P.; et al. Donor Dependent Variations in Hematopoietic Differentiation among Embryonic and Induced Pluripotent Stem Cell Lines. PLoS ONE 2016, 11, e0149291.
  66. Poetsch, M.S.; Strano, A.; Guan, K. Human Induced Pluripotent Stem Cells: From Cell Origin, Genomic Stability, and Epigenetic Memory to Translational Medicine. Stem Cells 2022, 40, 546–555.
  67. Turinetto, V.; Orlando, L.; Giachino, C. Induced Pluripotent Stem Cells: Advances in the Quest for Genetic Stability during Reprogramming Process. Int. J. Mol. Sci. 2017, 18, 1952.
  68. Efrat, S. Epigenetic Memory: Lessons From iPS Cells Derived From Human β Cells. Front. Endocrinol. 2021, 11, 1063.
  69. Bar, S.; Benvenisty, N. Epigenetic aberrations in human pluripotent stem cells. EMBO J. 2019, 38, e101033.
  70. Sacco, A.M.; Belviso, I.; Romano, V.; Carfora, A.; Schonauer, F.; Nurzynska, D.; Montagnani, S.; Di Meglio, F.; Castaldo, C. Diversity of dermal fibroblasts as major determinant of variability in cell reprogramming. J. Cell. Mol. Med. 2019, 23, 4256–4268.
  71. Ortmann, D.; Vallier, L. Variability of human pluripotent stem cell lines. Curr. Opin. Genet. Dev. 2017, 46, 179–185.
  72. Chang, C.Y.; Ting, H.C.; Liu, C.A.; Su, H.L.; Chiou, T.W.; Harn, H.J.; Lin, S.Z.; Ho, T.J. Differentiation of Human Pluripotent Stem Cells Into Specific Neural Lineages. Cell Transplant. 2021, 30, 09636897211017829.
  73. Rouhani, F.J.; Zou, X.; Danecek, P.; Badja, C.; Amarante, T.D.; Koh, G.; Wu, Q.; Memari, Y.; Durbin, R.; Martincorena, I.; et al. Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells. Nat. Genet. 2022, 54, 1406–1416.
  74. Lodrini, A.M.; Barile, L.; Rocchetti, M.; Altomare, C. Human Induced Pluripotent Stem Cells Derived from a Cardiac Somatic Source: Insights for an In-Vitro Cardiomyocyte Platform. Int. J. Mol. Sci. 2020, 21, 507.
  75. Shi, Y.; Inoue, H.; Wu, J.C.; Yamanaka, S. Induced pluripotent stem cell technology: A decade of progress. Nat. Rev. Drug Discov. 2017, 16, 115–130.
  76. Logan, S.; Arzua, T.; Canfield, S.G.; Seminary, E.R.; Sison, S.L.; Ebert, A.D.; Bai, X. Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models. Compr. Physiol. 2019, 9, 565–611.
  77. Hirschi, K.K.; Li, S.; Roy, K. Induced pluripotent stem cells for regenerative medicine. Annu. Rev. Biomed. Eng. 2014, 16, 277–294.
  78. Chang, N.C. Autophagy and Stem Cells: Self-Eating for Self-Renewal. Front. Cell Dev. Biol. 2020, 8, 138.
  79. Lee, C.-T.; Bendriem, R.M.; Wu, W.W.; Shen, R.-F. 3D brain Organoids derived from pluripotent stem cells: Promising experimental models for brain development and neurodegenerative disorders. J. Biomed. Sci. 2017, 24, 59.
  80. Mahla, R.S. Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. Int. J. Cell Biol. 2016, 2016, 6940283.
  81. Suman, S.; Domingues, A.; Ratajczak, J.; Ratajczak, M.Z. Potential Clinical Applications of Stem Cells in Regenerative Medicine. Adv. Exp. Med. Biol. 2019, 1201, 1–22.
  82. Li, S.; Yang, K.; Chen, X.; Zhu, X.; Zhou, H.; Li, P.; Chen, Y.; Jiang, Y.; Li, T.; Qin, X.; et al. Simultaneous 2D and 3D cell culture array for multicellular geometry, drug discovery and tumor microenvironment reconstruction. Biofabrication 2021, 13, 045013.
  83. Muguruma, M.; Teraoka, S.; Miyahara, K.; Ueda, A.; Asaoka, M.; Okazaki, M.; Kawate, T.; Kuroda, M.; Miyagi, Y.; Ishikawa, T. Differences in drug sensitivity between two-dimensional and three-dimensional culture systems in triple-negative breast cancer cell lines. Biochem. Biophys. Res. Commun. 2020, 533, 268–274.
  84. Chaubey, A.; Ross, K.J.; Leadbetter, R.M.; Burg, K.J.L. Surface patterning: Tool to modulate stem cell differentiation in an adipose system. J. Biomed. Mater. Res. Part B Appl. Biomater. 2008, 84, 70–78.
  85. Mabry, K.M.; Payne, S.Z.; Anseth, K.S. Microarray analyses to quantify advantages of 2D and 3D hydrogel culture systems in maintaining the native valvular interstitial cell phenotype. Biomaterials 2016, 74, 31–41.
  86. Xu, X.; Wang, W.; Kratz, K.; Fang, L.; Li, Z.; Kurtz, A.; Ma, N.; Lendlein, A. Controlling major cellular processes of human mesenchymal stem cells using microwell structures. Adv. Healthc. Mater. 2014, 3, 1991–2003.
  87. Jensen, C.; Teng, Y. Is It Time to Start Transitioning From 2D to 3D Cell Culture? Front. Mol. Biosci. 2020, 7, 33.
  88. Crosnier, C.; Staudt, N.; Wright, G.J. A rapid and scalable method for selecting recombinant mouse monoclonal antibodies. BMC Biol. 2010, 8, 76.
  89. Carrillo-Cocom, L.M.; Genel-Rey, T.; Araíz-Hernández, D.; López-Pacheco, F.; López-Meza, J.; Rocha-Pizaña, M.D.R.; Ramírez-Medrano, A.; Alvarez, M.M. Amino acid consumption in naïve and recombinant CHO cell cultures: Producers of a monoclonal antibody. Cytotechnology 2015, 67, 809–820.
  90. Jung-Klawitter, S.; Opladen, T. Induced pluripotent stem cells (iPSCs) as model to study inherited defects of neurotransmission in inborn errors of metabolism. J. Inherit. Metab. Dis. 2018, 41, 1103–1116.
  91. Mitra, A.; Mishra, L.; Li, S. Technologies for deriving primary tumor cells for use in personalized cancer therapy. Trends Biotechnol. 2013, 31, 347–354.
  92. Hsieh, C.-F.; Yan, Z.; Schumann, R.G.; Milz, S.; Pfeifer, C.G.; Schieker, M.; Docheva, D. In Vitro Comparison of 2D-Cell Culture and 3D-Cell Sheets of Scleraxis-Programmed Bone Marrow Derived Mesenchymal Stem Cells to Primary Tendon Stem/Progenitor Cells for Tendon Repair. Int. J. Mol. Sci. 2018, 19, 2272.
  93. Jin, L.; Qu, Y.; Gomez, L.J.; Chung, S.; Han, B.; Gao, B.; Yue, Y.; Gong, Y.; Liu, X.; Amersi, F.; et al. Characterization of primary human mammary epithelial cells isolated and propagated by conditional reprogrammed cell culture. Oncotarget 2018, 9, 11503–11514.
  94. Yin, Y.; Zhou, D. Organoid and enteroid modeling of Salmonella Infection. Front. Cell. Infect. Microbiol. 2018, 8, 102.
  95. Poon, A.; Zhang, Y.; Chandrasekaran, A.; Phanthong, P.; Schmid, B.; Nielsen, T.T.; Freude, K.K. Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges. New Biotechnol. 2017, 39, 190–198.
  96. Townsley, K.G.; Brennand, K.J.; Huckins, L.M. Massively parallel techniques for cataloguing the regulome of the human brain. Nat. Neurosci. 2020, 23, 1509–1521.
  97. Baxter, M.; Withey, S.; Harrison, S.; Segeritz, C.-P.; Zhang, F.; Atkinson-Dell, R.; Rowena, S.-Y.; Gerrard, D.T.; Sison-Young, R.; Jenkins, R.; et al. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. J. Hepatol. 2015, 62, 581–589.
  98. Fontoura, J.C.; Viezzer, C.; dos Santos, F.G.; Ligabue, R.A.; Weinlich, R.; Puga, R.D.; Antonow, D.; Severino, P.; Bonorino, C. Comparison of 2D and 3D cell culture models for cell growth, gene expression and drug resistance. Mater. Sci. Eng. C 2020, 107, 110264.
  99. Li, D.-W.; He, F.-L.; He, J.; Deng, X.; Liu, Y.-L.; Liu, Y.-Y.; Ye, Y.-J.; Yin, D.-C. From 2D to 3D: The morphology, proliferation and differentiation of MC3T3-E1 on silk fibroin/chitosan matrices. Carbohydr. Polym. 2017, 178, 69–77.
  100. Langhans, S.A. Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front. Pharmacol. 2018, 9, 6.
  101. Paşca, A.M.; Sloan, S.A.; Clarke, L.E.; Tian, Y.; Makinson, C.D.; Huber, N.; Kim, C.H.; Park, J.-Y.; O’Rourke, N.A.; Nguyen, K.D.; et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat. Methods 2015, 12, 671–678.
  102. Padmalayam, I.; Suto, M.J. 3D Cell Cultures: Mimicking In Vivo Tissues for Improved Predictability in Drug Discovery. Annu. Rep. Med. Chem. 2012, 47, 367–378.
  103. Zeng, Y.; Win-Shwe, T.-T.; Ito, T.; Sone, H. A three-dimensional neurosphere system using human stem cells for nanotoxicology studies. In Organoids and Mini-Organs; Academic Press: Cambridge, MA, USA, 2018; pp. 215–226.
  104. Yang, H.; Shao, N.; Holmström, A.; Zhao, X.; Chour, T.; Chen, H.; Itzhaki, I.; Wu, H.; Ameen, M.; Cunningham, N.J.; et al. Transcriptome analysis of non human primate-induced pluripotent stem cell-derived cardiomyocytes in 2D monolayer culture vs. 3D engineered heart tissue. Cardiovasc. Res. 2021, 117, 2125–2136.
  105. Kim, B.-C.; Kwack, K.; Chun, J.; Lee, J.-H. Comparative transcriptome analysis of human adipose-derived stem cells undergoing osteogenesis in 2D and 3D culture conditions. Int. J. Mol. Sci. 2021, 22, 7939.
  106. Nassor, F.; Jarray, R.; Biard, D.S.F.; Maïza, A.; Papy-Garcia, D.; Pavoni, S.; Deslys, J.-P.; Yates, F. Long Term Gene Expression in Human Induced Pluripotent Stem Cells and Cerebral Organoids to Model a Neurodegenerative Disease. Front. Cell. Neurosci. 2020, 14, 14.
  107. Yanagi, T.; Kajiya, H.; Fujisaki, S.; Maeshiba, M.; Yanagi, S.A.; Yamamoto-M, N.; Kakura, K.; Kido, H.; Ohno, J. Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration. Regen. Ther. 2021, 18, 472–479.
  108. Zhu, Y.; Kang, E.; Wilson, M.; Basso, T.; Chen, E.; Yu, Y.; Li, Y.-R. 3D Tumor Spheroid and Organoid to Model Tumor Microenvironment for Cancer Immunotherapy. Organoids 2022, 1, 12.
  109. Tuveson, D.A.; Clevers, H. Cancer modeling meets human organoid technology. Science 2019, 364, 952–955.
  110. Hofer, M.; Lutolf, M.P. Engineering organoids. Nat. Rev. Mater. 2021, 6, 402–420.
  111. Parihar, A.; Pandita, V.; Khan, R. 3D printed human organoids: High throughput system for drug screening and testing in current COVID-19 pandemic. Biotechnol. Bioeng. 2022, 119, 2669–2688.
  112. Shabalina, E.Y.; Skorova, E.Y.; Chudakova, D.A.; Anikin, V.B.; Reshetov, I.V.; Mynbaev, O.A.; Petersen, E.V. The matrix-dependent 3D spheroid model of the migration of non-small cell lung cancer: A step towards a rapid automated screening. Front. Pharmacol. 2021, 8, 115.
  113. Nath, S.; Devi, G.R. Three-Dimensional Culture Systems in Cancer Research: Focus on Tumor Spheroid Model. Pharmacol. Ther. 2016, 163, 94–108.
  114. Filipiak-Duliban, A.; Brodaczewska, K.; Kajdasz, A.; Kieda, C. Spheroid Culture Differentially Affects Cancer Cell Sensitivity to Drugs in Melanoma and RCC Models. Int. J. Mol. Sci. 2022, 23, 1166.
  115. Liao, W.; Wang, J.; Xu, J.; You, F.; Pan, M.; Xu, X.; Weng, J.; Han, X.; Li, S.; Li, Y.; et al. High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool. J. Tissue Eng. 2019, 10, 2041731419889184.
  116. Wang, P.; Sun, Y.; Shi, X.; Shen, H.; Ning, H.; Liu, H. 3D printing of tissue engineering scaffolds: A focus on vascular regeneration. Bio-Des. Manuf. 2021, 4, 344–378.
  117. Shabbirahmed, A.M.; Sekar, R.; Gomez, L.A.; Sekhar, M.R.; Hiruthyaswamy, S.P.; Basavegowda, N.; Somu, P. Recent Developments of Silk-Based Scaffolds for Tissue Engineering and Regenerative Medicine Applications: A Special Focus on the Advancement of 3D Printing. Biomimetics 2023, 8, 16.
  118. Chowdhury, S.R.; Lokanathan, Y.; Xian, L.J.; Busra, F.M.; Yazid, M.D.; Sulaiman, N.; Lahiry, G.; Hoque, E. 3D Printed Bioscaffolds for Developing Tissue-Engineered Constructs. In Design and Manufacturing; IntechOpen: London, UK, 2020.
  119. Chioni, A.-M.; Bajwa, R.T.; Grose, R. 3D Organotypic Culture Model to Study Components of ERK Signaling. Methods Mol. Biol. 2017, 1487, 255–267.
  120. De Gregorio, V.; La Rocca, A.; Urciuolo, F.; Annunziata, C.; Tornesello, M.L.; Buonaguro, F.M.; Netti, P.A.; Imparato, G. Modeling the epithelial-mesenchymal transition process in a 3D organotypic cervical neoplasia. Acta Biomater. 2020, 116, 209–222.
  121. Vernazza, S.; Tirendi, S.; Scarfì, S.; Passalacqua, M.; Oddone, F.; Traverso, C.E.; Rizzato, I.; Bassi, A.M.; Saccà, S. 2D- and 3D-cultures of human trabecular meshwork cells: A preliminary assessment of an in vitro model for glaucoma study. PLoS ONE 2019, 14, e0221942.
  122. Muguruma, K.; Nishiyama, A.; Kawakami, H.; Hashimoto, K.; Sasai, Y. Self-Organization of Polarized Cerebellar Tissue in 3D Culture of Human Pluripotent Stem Cells. Cell Rep. 2015, 10, 537–550.
  123. Kim, Y.H.; Choi, S.H.; D’Avanzo, C.; Hebisch, M.; Sliwinski, C.; Bylykbashi, E.; Washicosky, K.J.; Klee, J.B.; Brüstle, O.; Tanzi, R.E.; et al. A 3D human neural cell culture system for modeling Alzheimer’s disease. Nat. Protoc. 2015, 10, 985–1006.
  124. Choi, S.H.; Kim, Y.H.; Quinti, L.; Tanzi, R.E.; Kim, D.Y. 3D culture models of Alzheimer’s disease: A road map to a ‘cure-in-a-dish’. Mol. Neurodegener. 2016, 11, 75.
  125. Chen, H.J.; Miller, P.; Shuler, M.L. A pumpless body-on-a-chip model using a primary culture of human intestinal cells and a 3D culture of liver cells. Lab Chip 2018, 18, 2036–2046.
  126. Lv, D.; Hu, Z.; Lu, L.; Lu, H.; Xu, X. Three-dimensional cell culture: A powerful tool in tumor research and drug discovery (Review). Oncol. Lett. 2017, 14, 6999–7010.
  127. Danielson, J.J.; Perez, N.; Romano, J.D.; Coppens, I. Modelling Toxoplasma gondii infection in a 3D cell culture system In Vitro: Comparison with infection in 2D cell monolayers. PLoS ONE 2018, 13, e0208558.
  128. Park, S.E.; Georgescu, A.; Huh, D. Organoids-on-a-chip. Science 2019, 364, 960–965.
  129. Li, X.; Ootani, A.; Kuo, C. An air–liquid interface culture system for 3D organoid culture of diverse primary gastrointestinal tissues. Methods Mol. Biol. 2016, 1422, 33–40.
  130. Esser, L.K.; Branchi, V.; Leonardelli, S.; Pelusi, N.; Simon, A.G.; Klümper, N.; Ellinger, J.; Hauser, S.; Gonzalez-Carmona, M.A.; Ritter, M.; et al. Cultivation of Clear Cell Renal Cell Carcinoma Patient-Derived Organoids in an Air-Liquid Interface System as a Tool for Studying Individualized Therapy. Front. Oncol. 2020, 10, 1775.
  131. Giandomenico, S.L.; Mierau, S.B.; Gibbons, G.M.; Wenger, L.M.D.; Masullo, L.; Sit, T.; Sutcliffe, M.; Boulanger, J.; Tripodi, M.; Derivery, E.; et al. Cerebral organoids at the air–liquid interface generate diverse nerve tracts with functional output. Nat. Neurosci. 2019, 22, 669–679.
  132. Lin, Y.; Jiang, L.; He, Q.; Yuan, M.; Cao, J. Progress and perspective of organoid technology in cancer-related translational medicine. Biomed. Pharmacother. 2022, 149, 112869.
  133. Turhan, A.G.; Hwang, J.W.; Chaker, D.; Tasteyre, A.; Latsis, T.; Griscelli, F.; Desterke, C.; Bennaceur-Griscelli, A. iPSC-Derived Organoids as Therapeutic Models in Regenerative Medicine and Oncology. Front. Med. 2021, 8, 1838.
  134. Luo, C.; Lancaster, M.A.; Castanon, R.; Nery, J.R.; Knoblich, J.A.; Ecker, J.R. Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain. Cell Rep. 2016, 17, 3369–3384.
  135. Sun, L.; Hui, L. Progress in human liver organoids. J. Mol. Cell Biol. 2020, 12, 607–617.
  136. Balak, J.R.A.; Juksar, J.; Carlotti, F.; Nigro, A.L.; de Koning, E.J.P. Organoids from the Human Fetal and Adult Pancreas. Curr. Diabetes Rep. 2019, 19, 160.
  137. Puschhof, J.; Pleguezuelos-Manzano, C.; Clevers, H. Organoids and organs-on-chips: Insights into human gut-microbe interactions. Cell Host Microbe 2021, 29, 867–878.
  138. Manafi, N.; Shokri, F.; Achberger, K.; Hirayama, M.; Mohammadi, M.H.; Noorizadeh, F.; Hong, J.; Liebau, S.; Tsuji, T.; Quinn, P.M.; et al. Organoids and organ chips in ophthalmology. Ocul. Surf. 2020, 19, 1–15.
  139. Hsia, G.S.P.; Esposito, J.; da Rocha, L.A.; Ramos, S.L.G.; Okamoto, O.K. Clinical Application of Human Induced Pluripotent Stem Cell-Derived Organoids as an Alternative to Organ Transplantation. Stem Cells Int. 2021, 2021, 6632160.
  140. Sugimoto, S.; Kobayashi, E.; Fujii, M.; Ohta, Y.; Arai, K.; Matano, M.; Ishikawa, K.; Miyamoto, K.; Toshimitsu, K.; Takahashi, S.; et al. An organoid-based organ-repurposing approach to treat short bowel syndrome. Nature 2021, 592, 99–104.
  141. Zhao, Z.; Chen, X.; Dowbaj, A.M.; Sljukic, A.; Bratlie, K.; Lin, L.; Fong, E.L.S.; Balachander, G.M.; Chen, Z.; Soragni, A.; et al. Organoids. Nat. Rev. Methods Prim. 2022, 2, 94.
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Subjects: Cell & Tissue Engineering
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Rita Silva-Pedrosa
,
António José Salgado
,
Pedro Eduardo Ferreira
View Times: 658
Revisions: 2 times (View History)
Update Date: 30 May 2023
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