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In Vitro Models of Tissue and Organ Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 23334

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Special Issue Editors

Universitätsklinikum Frankfurt, Zentrum der Inneren Medizin - Nephrologie, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany
Interests: mesenchymal stromal/stem cells; acute kidney injury; renal tubular cells; adipose tissue; renal regeneration; extracellular vesicles
Special Issues, Collections and Topics in MDPI journals
Department of Pediatrics, J. W. Goethe University, Frankfurt/Main, Germany
Interests: pneumology; allergy; sputum; cell research

Special Issue Information

Dear Colleagues,

The recovery of cells after tissue and organ injury is a very complex process. To understand the underlying molecular biological mechanisms, more detailed insights into the cellular processes of repair and regeneration are urgently needed. Based on this knowledge, the focus of this Special Issue is on current in vitro systems exploring repair and regeneration mechanisms. We welcome experimental research approaches investigating the mechanisms involved and the laboratory methods used to establish and optimize in vitro models for tissue and organ repair and regeneration, with a focus on the role of (mesenchymal stromal) stem cells, (pre-)conditioned media and extracellular vesicles in regenerative medicine, which may result in greater success in clinical applications.

Therefore, this Special Issue welcomes original research and review papers addressing:

  1. In vitro models to investigate regenerative mechanisms during acute and chronic injury;
  2. In vitro models to investigate repair, fibrosis and scar formation; 
  3. In vitro preconditioning regimens to enhance the regenerative potential of cells;
  4. Co-culture systems of supportive cells (e.g., mesenchymal stromal/stem cells) with injured cells;
  5. Characterization of extracellular vesicles and exosomes and their effects on cell proliferation and differentiation;
  6. Organoid cultures;
  7. RNA-seq-based transcriptional profiling of in vitro models;
  8. Proteomics based translatomic profiling of in vitro models;
  9. Investigations of the epigenetic regulation such as specific miRNA and ncRNA in these processes.

Prof. Dr. Patrick C. Baer
Prof. Dr. Ralf Schubert
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tissue and organ injury
  • in vitro models
  • repair
  • regeneration
  • epithelial cells and cell differentiation
  • lung injury, acute and chronic kidney injury
  • mesenchymal stromal/stem cells
  • organoids,
  • preconditioning regimens, conditioned medium
  • extracellular vesicles
  • angiogenesis

Published Papers (12 papers)

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Editorial

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3 pages, 186 KiB  
Editorial
In Vitro Models of Tissue and Organ Regeneration
by Patrick C. Baer and Ralf Schubert
Int. J. Mol. Sci. 2023, 24(19), 14592; https://doi.org/10.3390/ijms241914592 - 26 Sep 2023
Viewed by 430
Abstract
The recovery of cells after tissue and organ injury is a complex process [...] Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)

Research

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15 pages, 2553 KiB  
Article
microRNA Expression of Renal Proximal Tubular Epithelial Cells and Their Extracellular Vesicles in an Inflammatory Microenvironment In Vitro
by Patrick C. Baer, Ann-Kathrin Neuhoff and Ralf Schubert
Int. J. Mol. Sci. 2023, 24(13), 11069; https://doi.org/10.3390/ijms241311069 - 04 Jul 2023
Cited by 2 | Viewed by 1198
Abstract
Renal proximal tubular epithelial cells (PTCs) are central players during renal inflammation. In response to inflammatory signals, PTCs not only self-express altered mRNAs, microRNAs (miRNAs), proteins, and lipids, but also release altered extracellular vesicles (EVs). These EVs also carry inflammation-specific cargo molecules and [...] Read more.
Renal proximal tubular epithelial cells (PTCs) are central players during renal inflammation. In response to inflammatory signals, PTCs not only self-express altered mRNAs, microRNAs (miRNAs), proteins, and lipids, but also release altered extracellular vesicles (EVs). These EVs also carry inflammation-specific cargo molecules and are key players in cell–cell-communication. Understanding the precise molecular and cellular mechanisms that lead to inflammation in the kidney is the most important way to identify early targets for the prevention or treatment of acute kidney injury. Therefore, highly purified human PTCs were used as an in vitro model to study the cellular response to an inflammatory microenvironment. A cytokine-induced inflammatory system was established to analyze different miRNA expression in cells and their EVs. In detail, we characterized the altered miR expression of PTCs and their released EVs during induced inflammation and showed that 12 miRNAs were significantly regulated in PTCs (6 upregulated and 6 downregulated) and 9 miRNAs in EVs (8 upregulated and 1 downregulated). We also showed that only three of the miRNAs were found to overlap between cells and EVs. As shown by the KEGG pathway analysis, these three miRNAs (miR-146a-5p, miR-147b, and miR-155-5p) are functionally involved in the regulation of the Toll-like receptor signaling pathway and significantly correlated with the inflammatory mediators IL6 and ICAM1 released by stimulated PTCs. Especially with regard to a possible clinical use of miRs as new biomarkers, an accurate characterization of the miR expression altered during inflammatory processes is of enormous importance. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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27 pages, 6965 KiB  
Article
Determination of Krogh Coefficient for Oxygen Consumption Measurement from Thin Slices of Rodent Cortical Tissue Using a Fick’s Law Model of Diffusion
by D. Alistair Steyn-Ross, Moira L. Steyn-Ross, Jamie W. Sleigh and Logan J. Voss
Int. J. Mol. Sci. 2023, 24(7), 6450; https://doi.org/10.3390/ijms24076450 - 29 Mar 2023
Cited by 3 | Viewed by 1327
Abstract
To investigate the impact of experimental interventions on living biological tissue, ex vivo rodent brain slices are often used as a more controllable alternative to a live animal model. However, for meaningful results, the biological sample must be known to be healthy and [...] Read more.
To investigate the impact of experimental interventions on living biological tissue, ex vivo rodent brain slices are often used as a more controllable alternative to a live animal model. However, for meaningful results, the biological sample must be known to be healthy and viable. One of the gold-standard approaches to identifying tissue viability status is to measure the rate of tissue oxygen consumption under specific controlled conditions. Here, we work with thin (400 μm) slices of mouse cortical brain tissue which are sustained by a steady flow of oxygenated artificial cerebralspinal fluid (aCSF) at room temperature. To quantify tissue oxygen consumption (Q), we measure oxygen partial pressure (pO2) as a function of probe depth. The curvature of the obtained parabolic (or parabola-like) pO2 profiles can be used to extract Q, providing one knows the Krogh coefficient Kt, for the tissue. The oxygen trends are well described by a Fick’s law diffusion–consumption model developed by Ivanova and Simeonov, and expressed in terms of ratio (Q/K), being the rate of oxygen consumption in tissue divided by the Krogh coefficient (oxygen diffusivity × oxygen solubility) for tissue. If the fluid immediately adjacent to the tissue can be assumed to be stationary (i.e., nonflowing), one may invoke conservation of oxygen flux K·(P/x) across the interface to deduce (Kt/Kf), the ratio of Krogh coefficients for tissue and fluid. Using published interpolation formulas for the effect of salt content and temperature on oxygen diffusivity and solubility for pure water, we estimate Kf, the Krogh coefficient for aCSF, and hence deduce the Kt coefficient for tissue. We distinguish experimental uncertainty from natural biological variability by using pairs of repeated profiles at the same tissue location. We report a dimensionless Krogh ratio (Kt/Kf)=0.562±0.088 (mean ± SD), corresponding to a Krogh coefficient Kt=(1.29±0.21)×1014 mol/(m·s·Pa) for mouse cortical tissue at room temperature, but acknowledge the experimental limitation of being unable to verify that the fluid boundary layer is truly stationary. We compare our results with those reported in the literature, and comment on the challenges and ambiguities caused by the extensive use of ‘biologically convenient’ non-SI units for tissue Krogh coefficient. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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18 pages, 2974 KiB  
Article
Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats
by Marisa Esteves-Monteiro, Daniela Menezes-Pinto, Mariana Ferreira-Duarte, Patrícia Dias-Pereira, Manuela Morato and Margarida Duarte-Araújo
Int. J. Mol. Sci. 2022, 23(21), 13233; https://doi.org/10.3390/ijms232113233 - 31 Oct 2022
Cited by 3 | Viewed by 1491
Abstract
Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in [...] Read more.
Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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24 pages, 7474 KiB  
Article
Convolutional Neural Network Model Based on 2D Fingerprint for Bioactivity Prediction
by Hamza Hentabli, Billel Bengherbia, Faisal Saeed, Naomie Salim, Ibtehal Nafea, Abdelmoughni Toubal and Maged Nasser
Int. J. Mol. Sci. 2022, 23(21), 13230; https://doi.org/10.3390/ijms232113230 - 30 Oct 2022
Cited by 3 | Viewed by 1781
Abstract
Determining and modeling the possible behaviour and actions of molecules requires investigating the basic structural features and physicochemical properties that determine their behaviour during chemical, physical, biological, and environmental processes. Computational approaches such as machine learning methods are alternatives to predicting the physiochemical [...] Read more.
Determining and modeling the possible behaviour and actions of molecules requires investigating the basic structural features and physicochemical properties that determine their behaviour during chemical, physical, biological, and environmental processes. Computational approaches such as machine learning methods are alternatives to predicting the physiochemical properties of molecules based on their structures. However, the limited accuracy and high error rates of such predictions restrict their use. In this paper, a novel technique based on a deep learning convolutional neural network (CNN) for the prediction of chemical compounds’ bioactivity is proposed and developed. The molecules are represented in the new matrix format Mol2mat, a molecular matrix representation adapted from the well-known 2D-fingerprint descriptors. To evaluate the performance of the proposed methods, a series of experiments were conducted using two standard datasets, namely the MDL Drug Data Report (MDDR) and Sutherland, datasets comprising 10 homogeneous and 14 heterogeneous activity classes. After analysing the eight fingerprints, all the probable combinations were investigated using the five best descriptors. The results showed that a combination of three fingerprints, ECFP4, EPFP4, and ECFC4, along with a CNN activity prediction process, achieved the highest performance of 98% AUC when compared to the state-of-the-art ML algorithms NaiveB, LSVM, and RBFN. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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15 pages, 3354 KiB  
Article
Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits
by Shofiul Azam, Yon-Suk Kim, Md. Jakaria, Ye-Ji Yu, Jae-Yong Ahn, In-Su Kim and Dong-Kug Choi
Int. J. Mol. Sci. 2022, 23(17), 9923; https://doi.org/10.3390/ijms23179923 - 01 Sep 2022
Cited by 3 | Viewed by 2124
Abstract
Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many neurodegenerative disease progressions. Dioscorea nipponica Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism [...] Read more.
Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many neurodegenerative disease progressions. Dioscorea nipponica Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism of action in microglial cells remain unknown. The current study investigates the possible anti-inflammatory effects and mechanisms of Dioscorea nipponica Makino ethanol extract and its steroidal saponin dioscin. Our in vitro study shows that Dioscorea nipponica rhizome ethanol extract (DNRE) and dioscin protect against lipopolysaccharide (LPS)-activated inflammatory responses in BV-2 microglial cells by inhibiting phosphorylation and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in the downregulation of pro-inflammatory cytokines and enzymes. Consistent with our previous report of dioscin-mediated enhancement of neurotrophic factors in dopaminergic cells, here we found that dioscin upregulates brain-derived neurotrophic factor (BDNF) and cAMP-response element binding protein (CREB) phosphorylation (pCREB) in the cerebral cortex and hippocampus regions of the mouse brain. Scopolamine treatment increased pro-inflammatory enzyme levels and reduced the expression of BDNF and pCREB in the hippocampus and cortex regions, which led to impaired learning and referencing memory in mice. Pre-treatment of dioscin for 7 days substantially enhanced mice performances in maze studies, indicating amelioration in cognitive deficits. In conclusion, DNRE and its active compound dioscin protect against neurotoxicity most likely by suppressing NF-κB phosphorylation and upregulating neurotrophic factor BDNF. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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15 pages, 2498 KiB  
Article
In Vitro Conditioning of Adipose-Derived Mesenchymal Stem Cells by the Endothelial Microenvironment: Modeling Cell Responsiveness towards Non-Genetic Correction of Haemophilia A
by Silvia Barbon, Elena Stocco, Senthilkumar Rajendran, Lorena Zardo, Veronica Macchi, Claudio Grandi, Giuseppe Tagariello, Andrea Porzionato, Paolo Radossi, Raffaele De Caro and Pier Paolo Parnigotto
Int. J. Mol. Sci. 2022, 23(13), 7282; https://doi.org/10.3390/ijms23137282 - 30 Jun 2022
Cited by 3 | Viewed by 1453
Abstract
In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are [...] Read more.
In recent decades, the use of adult multipotent stem cells has paved the way for the identification of new therapeutic approaches for the treatment of monogenic diseases such as Haemophilia A. Being already studied for regenerative purposes, adipose-derived mesenchymal stem cells (Ad-MSCs) are still poorly considered for Haemophilia A cell therapy and their capacity to produce coagulation factor VIII (FVIII) after proper stimulation and without resorting to gene transfection. In this work, Ad-MSCs were in vitro conditioned towards the endothelial lineage, considered to be responsible for coagulation factor production. The cells were cultured in an inductive medium enriched with endothelial growth factors for up to 21 days. In addition to significantly responding to the chemotactic endothelial stimuli, the cell populations started to form capillary-like structures and up-regulated the expression of specific endothelial markers (CD34, PDGFRα, VEGFR2, VE-cadherin, CD31, and vWF). A dot blot protein study detected the presence of FVIII in culture media collected from both unstimulated and stimulated Ad-MSCs. Remarkably, the activated partial thromboplastin time test demonstrated that the clot formation was accelerated, and FVIII activity was enhanced when FVIII deficient plasma was mixed with culture media from the untreated/stimulated Ad-MSCs. Overall, the collected evidence supported a possible Ad-MSC contribution to HA correction via specific stimulation by the endothelial microenvironment and without any need for gene transfection. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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11 pages, 4517 KiB  
Communication
Lung Extracellular Matrix Hydrogels Enhance Preservation of Type II Phenotype in Primary Alveolar Epithelial Cells
by Esther Marhuenda, Alvaro Villarino, Maria Leonor Narciso, Marta Camprubí-Rimblas, Ramon Farré, Núria Gavara, Antonio Artigas, Isaac Almendros and Jorge Otero
Int. J. Mol. Sci. 2022, 23(9), 4888; https://doi.org/10.3390/ijms23094888 - 28 Apr 2022
Cited by 9 | Viewed by 2198
Abstract
One of the main limitations of in vitro studies on lung diseases is the difficulty of maintaining the type II phenotype of alveolar epithelial cells in culture. This fact has previously been related to the translocation of the mechanosensing Yes-associated protein (YAP) to [...] Read more.
One of the main limitations of in vitro studies on lung diseases is the difficulty of maintaining the type II phenotype of alveolar epithelial cells in culture. This fact has previously been related to the translocation of the mechanosensing Yes-associated protein (YAP) to the nuclei and Rho signaling pathway. In this work, we aimed to culture and subculture primary alveolar type II cells on extracellular matrix lung-derived hydrogels to assess their suitability for phenotype maintenance. Cells cultured on lung hydrogels formed monolayers and maintained type II phenotype for a longer time as compared with those conventionally cultured. Interestingly, cells successfully grew when they were subsequently cultured on a dish. Moreover, cells cultured on a plate showed the active form of the YAP protein and the formation of stress fibers and focal adhesions. The results of chemically inhibiting the Rho pathway strongly suggest that this is one of the mechanisms by which the hydrogel promotes type II phenotype maintenance. These results regarding protein expression strongly suggest that the chemical and biophysical properties of the hydrogel have a considerable impact on the transition from ATII to ATI phenotypes. In conclusion, culturing primary alveolar epithelial cells on lung ECM-derived hydrogels may facilitate the prolonged culturing of these cells, and thus help in the research on lung diseases. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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12 pages, 1757 KiB  
Article
A New Perspective for Bone Tissue Engineering: Human Mesenchymal Stromal Cells Well-Survive Cryopreservation on β-TCP Scaffold and Show Increased Ability for Osteogenic Differentiation
by Liudmila Leppik, Anna Gempp, Zyrafete Kuçi, Selim Kuçi, Peter Bader, Halvard Bönig, Ingo Marzi and Dirk Henrich
Int. J. Mol. Sci. 2022, 23(3), 1425; https://doi.org/10.3390/ijms23031425 - 26 Jan 2022
Cited by 2 | Viewed by 2204
Abstract
The clinical breakthrough of bone tissue engineering (BTE) depends on the ability to provide patients routinely with BTE products of consistent pharmacological quality. The bottleneck of this approach is the availability of stem cells. To avoid this, we suggest immobilization of random-donor-derived heterologous [...] Read more.
The clinical breakthrough of bone tissue engineering (BTE) depends on the ability to provide patients routinely with BTE products of consistent pharmacological quality. The bottleneck of this approach is the availability of stem cells. To avoid this, we suggest immobilization of random-donor-derived heterologous osteoinductive MSCs onto osteoconductive matrices. Such BTE products could then be frozen and, after thawing, could be released as ready-to-use products for permanent implantation during surgery. For this purpose, we developed a simple protocol for cryopreservation of BTE constructs and evaluated the effects of this procedure on human MSC (hMSCs) metabolic and osteogenic activity in vitro. Our findings show that hMSCs can be freeze-thawed on a β-TCP scaffold through a technically simple procedure. Treated cells sustained their metabolic activity and showed favorable osteogenic potential. Mechanistically, HIF1α and YBX1 genes were activated after freeze-thawing, and supposed to be linked to enhanced osteogenesis. However, the detailed mechanisms as to how the cryopreservation procedure beneficially affects the osteogenic potential of hMSCs remains to be evaluated. Additionally, we demonstrated that our BTE products could be stored for 3 days on dry ice; this could facilitate the supply chain management of cryopreserved BTE constructs from the site of manufacture to the operating room. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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Review

Jump to: Editorial, Research

28 pages, 3999 KiB  
Review
Fabrication and Characterization Techniques of In Vitro 3D Tissue Models
by Rohin Shyam, L. Vinod Kumar Reddy and Arunkumar Palaniappan
Int. J. Mol. Sci. 2023, 24(3), 1912; https://doi.org/10.3390/ijms24031912 - 18 Jan 2023
Cited by 6 | Viewed by 2919
Abstract
The culturing of cells in the laboratory under controlled conditions has always been crucial for the advancement of scientific research. Cell-based assays have played an important role in providing simple, fast, accurate, and cost-effective methods in drug discovery, disease modeling, and tissue engineering [...] Read more.
The culturing of cells in the laboratory under controlled conditions has always been crucial for the advancement of scientific research. Cell-based assays have played an important role in providing simple, fast, accurate, and cost-effective methods in drug discovery, disease modeling, and tissue engineering while mitigating reliance on cost-intensive and ethically challenging animal studies. The techniques involved in culturing cells are critical as results are based on cellular response to drugs, cellular cues, external stimuli, and human physiology. In order to establish in vitro cultures, cells are either isolated from normal or diseased tissue and allowed to grow in two or three dimensions. Two-dimensional (2D) cell culture methods involve the proliferation of cells on flat rigid surfaces resulting in a monolayer culture, while in three-dimensional (3D) cell cultures, the additional dimension provides a more accurate representation of the tissue milieu. In this review, we discuss the various methods involved in the development of 3D cell culture systems emphasizing the differences between 2D and 3D systems and methods involved in the recapitulation of the organ-specific 3D microenvironment. In addition, we discuss the latest developments in 3D tissue model fabrication techniques, microfluidics-based organ-on-a-chip, and imaging as a characterization technique for 3D tissue models. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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16 pages, 941 KiB  
Review
A Review of Defatting Strategies for Non-Alcoholic Fatty Liver Disease
by Erin Nicole Young, Murat Dogan, Christine Watkins, Amandeep Bajwa, James D. Eason, Canan Kuscu and Cem Kuscu
Int. J. Mol. Sci. 2022, 23(19), 11805; https://doi.org/10.3390/ijms231911805 - 05 Oct 2022
Cited by 5 | Viewed by 2403
Abstract
Non-alcoholic fatty liver disease is a huge cause of chronic liver failure around the world. This condition has become more prevalent as rates of metabolic syndrome, type 2 diabetes, and obesity have also escalated. The unfortunate outcome for many people is liver cirrhosis [...] Read more.
Non-alcoholic fatty liver disease is a huge cause of chronic liver failure around the world. This condition has become more prevalent as rates of metabolic syndrome, type 2 diabetes, and obesity have also escalated. The unfortunate outcome for many people is liver cirrhosis that warrants transplantation or being unable to receive a transplant since many livers are discarded due to high levels of steatosis. Over the past several years, however, a great deal of work has gone into understanding the pathophysiology of this disease as well as possible treatment options. This review summarizes various defatting strategies including in vitro use of pharmacologic agents, machine perfusion of extracted livers, and genomic approaches targeting specific proteins. The goal of the field is to reduce the number of necessary transplants and expand the pool of organs available for use. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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18 pages, 1494 KiB  
Review
Looking into the Eyes—In Vitro Models for Ocular Research
by Krystyna Lieto, Rafał Skopek, Aneta Lewicka, Marta Stelmasiak, Emilia Klimaszewska, Arthur Zelent, Łukasz Szymański and Sławomir Lewicki
Int. J. Mol. Sci. 2022, 23(16), 9158; https://doi.org/10.3390/ijms23169158 - 15 Aug 2022
Cited by 7 | Viewed by 2753
Abstract
Animal research undoubtedly provides scientists with virtually unlimited data but inflicts pain and suffering on animals. Currently, legislators and scientists alike are promoting alternative in vitro approaches allowing for an accurate evaluation of processes occurring in the body without animal sacrifice. Historically, one [...] Read more.
Animal research undoubtedly provides scientists with virtually unlimited data but inflicts pain and suffering on animals. Currently, legislators and scientists alike are promoting alternative in vitro approaches allowing for an accurate evaluation of processes occurring in the body without animal sacrifice. Historically, one of the most infamous animal tests is the Draize test, mainly performed on rabbits. Even though this test was considered the gold standard for around 50 years, the Draize test fails to mimic human response mainly due to human and rabbit eye physiological differences. Therefore, many alternative assays were developed to evaluate ocular toxicity and drug effectiveness accurately. Here we review recent achievements in tissue engineering of in vitro 2D, 2.5D, 3D, organoid and organ-on-chip ocular models, as well as in vivo and ex vivo models in terms of their advantages and limitations. Full article
(This article belongs to the Special Issue In Vitro Models of Tissue and Organ Regeneration)
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