Skin organoids: A new human model for developmental and translational research

Lee, Jiyoon; Koehler, Karl R.

doi:10.1111/exd.14292

Cited by 43 publications

(38 citation statements)

References 84 publications

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“…Skin is the largest as well as the most superficial organ to endure diverse physical and chemical assaults, particularly from topical formulations. Skin organoids generated from diverse sources bear paramount importance in several skin-related disease modeling, regenerative medicine, and drug efficacy as well as toxicity testing ( Lei et al, 2017 ; Lee et al, 2020 ; Lee and Koehler, 2021 ). The developmental process of the mouse skin organoid deciphers valuable insight in regenerative medicine as it prospers the path of microenvironmental reprogramming toward restoration of the self-organizing property of adult skin.…”

Section: Skin Organoidsmentioning

confidence: 99%

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

Prasad

Kumar

Buragohain

et al. 2021

Front. Cell Dev. Biol.

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Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.

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Section: Skin Organoidsmentioning

confidence: 99%

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

Prasad

Kumar

Buragohain

et al. 2021

Front. Cell Dev. Biol.

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“…Nevertheless, no immune cells, such as Langerhans cells (LCs), were detected in these skin organoids. It is possible to improve our understanding of different cell types and states, as well as their specific pathways, by mining large datasets of single-cell gene expression profiles in this research ( Lee et al, 2018 ; Lee et al, 2020 ; Lee and Koehler, 2021 ). A recent single-cell analysis identified new subpopulations of basal cells located at the top or bottom of the reticular dermis and reported that cell fate specification is determined by the expression of lineage-specific transcription factors ( Matsumura et al, 2021 ).…”

Section: Sources Of Skin Cells and The Generation Of Skin Organoidsmentioning

confidence: 99%

“…hiPSCs can become ideal sources of cells for generating skin organoids. Thus, it is evident that being able to recapitulate skin tissues in a dish has considerably broadened the scope of skin organoid applications, including the study of human skin development, disease modeling, drug testing, investigating skin barrier biology, the development of cell/gene therapies, and toxicological assessments ( Niehues et al, 2018 ; Lee and Koehler, 2021 ) ( Figure 1B ).…”

Section: The Applications Of Multifunctional Skin Organoidsmentioning

confidence: 99%

Generation of Skin Organoids: Potential Opportunities and Challenges

Sun

Zhang

2021

Front. Cell Dev. Biol.

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Although several types of human skin substitutes are currently available, they usually do not include important skin appendages such as hair follicles and sweat glands, or various skin-related cells, such as dermal adipocytes and sensory neurons. This highlights the need to improve the in vitro human skin generation model for use as a tool for investigating skin diseases and as a source of cells or tissues for skin regeneration. Skin organoids are generated from stem cells and are expected to possess the complexity and function of natural skin. Here, we summarize the current literatures relating to the “niches” of the local skin stem cell microenvironment and the formation of skin organoids, and then discuss the opportunities and challenges associated with multifunctional skin organoids.

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“…From gaining molecular insight into essential aspects of skin development and homeostasis to preclinical testing of new drug candidates for skin diseases to their use as "tissue farms" to grow new skin substitutes for burn and trauma patients, 3D cultures are becoming a mainstay approach both in basic and translational dermatological research (Figure 1). Current 3D culture technologies include the following: (i) free-floating cultures of spherical organoids initiated from pluripotent stem cells; (ii) layered constructs consecutively assembled by seeding primary skin cells into extracellular matrix scaffolds 38 to contain stratified epidermis, sebocyte spheroids 39 or hair pegs 40 ; (iii) freshly micro-dissected skin and hair follicle explant cultures [41][42][43][44] ; and (iv) organ-on-a-chip cultures that incorporate capillary structures and allow active perfusion using microfluidics. 45,46 However, so-called 3D skin "equivalent" cultures are not without limitations.…”

Section: What Org Anot Ypi C Culture S C An and C An ' T Domentioning

confidence: 99%

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

Atwood

Plikus

2021

Experimental Dermatology

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The field of experimental dermatology research has dramatically benefited from the insights yielded by in vivo studies on animal models. Indeed, much of our understanding of the mechanisms that regulate embryonic skin development, adult skin homeostasis and physiological skin responses to stress, such as wound healing, has been educated by studies conducted in animal models, including mutant mice. These works become commonly published on the pages of Experimental Dermatology and, in fact, represent one of the core interests of the journal. Highlighting in vivo mouse model studies are recent works on hair follicle development and growth 1-5 and wound healing. 6-8 Further, studies in animal models often help to elucidate aspects of disease pathogenesis, and mouse models are used to investigate mechanisms of human skin conditions such as atopic dermatitis, 9-13 contact dermatitis, 14-16 psoriasis, 17,18 rosacea 19 and squamous cell carcinoma 20 to name a few. On the other hand, not all human skin diseases or aspects of human skin physiology can be reliably modelled in rodents. This is not surprising, considering that humans and rodents are separated by an estimated 96 million years of evolution. 21 Addressing this fact, many studies are being conducted on patient-derived primary skin cells, including human keratinocytes, 22-25 melanocytes, 26-30 fibroblasts 31-34 and cell co-cultures. 35-37 However, typical in vitro culture conditions fail to replicate and, in fact, do not come close to imitating the biomechanical and biochemical complexity of the microenvironment in which cells exist and to which they respond to in native tissues. Further, ingredients in commonly used cell culture media and the two-dimensional constraints of growth on plastic result in cells being exposed to a lot of artificial cues, to which they adapt but also prominently alter their gene expression profile and functional activities in the process. Therefore, behaviours displayed by skin cells in twodimensional cultures need to be comprehensively validated under more native-like conditions in order to be deemed biologically and physiologically relevant. Helping to bridge the gap, threedimensional (3D) organotypic cultures and organ culture techniques have long been a highly instructive tool for investigating complex, tissue-level behaviours by skin cells.

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Skin organoids: A new human model for developmental and translational research

Cited by 43 publications

References 84 publications

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

Generation of Skin Organoids: Potential Opportunities and Challenges

Fostering a healthy culture: Biological relevance of in vitro and ex vivo skin models

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