Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

Agarwal, Yash; Beatty, Cole; Ho, Sara; Thurlow, Lance; A, Das; Kelly, Samantha; Castronova, Isabella; Salunke, Rajeev; Biradar, Shivkumar; Yeshi, Tseten; Richardson, Anthony R.; Bility, Moses T.

doi:10.1038/s41598-020-71548-z

Cited by 15 publications

(13 citation statements)

References 63 publications

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“…Perhaps due to its critical role in various bodily functions, diseases of the skin are common, with >5.4 million cases of skin cancer every year and ~500,000 patients who receive treatment for burns or other skin trauma [6][7][8][9][10][11] . The mouse is a standard model for investigating skin development and disease in vivo [12][13][14][15][16][17] . Yet, there are critical differences between mouse and human skin, such as the mechanisms of wound closure, which have confounded efforts to translate therapies to the clinic 18 .…”

Section: Introductionmentioning

confidence: 99%

Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells

et al. 2022

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Human skin uses millions of hairs and glands distributed across the body surface to function as an external barrier, thermoregulator and stimuli sensor. The large-scale generation of human skin with these appendages would be beneficial, but is challenging. Here, we describe a detailed protocol for generating hair-bearing skin tissue entirely from a homogeneous population of human pluripotent stem cells in a three-dimensional in vitro culture system. Defined culture conditions are used over a 2-week period to induce differentiation of pluripotent stem cells to surface ectoderm and cranial neural crest cells, which give rise to the epidermis and dermis, respectively, in each organoid unit. After 60 d of incubation, the skin organoids produce hair follicles. By day ~130, the skin organoids reach full complexity and contain stratified skin layers, pigmented hair follicles, sebaceous glands, Merkel cells and sensory neurons, recapitulating the cell composition and architecture of fetal skin tissue at week 18 of gestation. Skin organoids can be maintained in culture using this protocol for up to 150 d, enabling the organoids to be used to investigate basic skin biology, model disease and, further, reconstruct or regenerate skin tissue.

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Section: Introductionmentioning

confidence: 99%

Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells

et al. 2022

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“…These studies primarily attempt to generate humanized rat models of various pathological conditions and tissue damage without using BC methods. With the emergence of new humanized rat models, the future of functional human-rat interspecies chimerism holds excellent promise, while the permissiveness of non-cancerous, normal human epithelial chimerism needs to be addressed well ( Agarwal et al, 2020 ).…”

Section: Interspecies Barriers In Chimerasmentioning

confidence: 99%

Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy

Sarmah

Sawada

Hwang

et al. 2023

Front. Cell Dev. Biol.

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Millions of people suffer from end-stage refractory diseases. The ideal treatment option for terminally ill patients is organ transplantation. However, donor organs are in absolute shortage, and sadly, most patients die while waiting for a donor organ. To date, no technology has achieved long-term sustainable patient-derived organ generation. In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology.

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“…Such models can be definitely a boon to study the immunomodulation in skin wound environments. 156 Hu et al developed an improvised humanized mouse model using a double transgenic mouse and fluorescence imaging to study the accurate healing time of wounds. They observed that macroscopic evaluation of wound showed a delay of 2 days in normal light as compared to fluorescent light and hence over estimation of wound closure time.…”

Section: Current Approaches Towards Wound Regenerationmentioning

confidence: 99%

Biomaterial mediated immunomodulation: An interplay of material environment interaction for ameliorating wound regeneration

et al. 2023

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Chronic wounds are the outcome of an imbalanced inflammatory response caused by sustenance of immune microenvironment. In this context, tissue engineered graft played great role in healing wounds but faced difficulty in scar remodelling, immune rejection and poor vascularization. All the limitations faced are somewhere linked with the immune cells involved in healing. In this consideration, immunomodulatory biomaterials bridge a large gap with the delivery of modulating factors for triggering key inflammatory cells responsible towards interplay in the wound micro-environment. Inherent physico-chemical properties of biomaterials substantially determine the nature of cell-materials interaction thereby facilitating differential cytokine gradient involved in activation or suppression of inflammatory signalling pathways, and followed by surface marker expression. This review aims to systematically describe the interplay of immune cells involved in different phases in the wound microenvironment and biomaterials. Additionally, it also focuses on modulating innate immune cell responses in the context of triggering the halted phase of the wound healing, i.e., inflammatory phase. The various strategies are highlighted for modulation of wound microenvironment towards wound regeneration including stem cells, cytokines, growth factors, vitamins, and anti-inflammatory agents to induce interactive ability of biomaterials with immune cells. The last section focuses on prospective approaches and current potential strategies for wound regeneration. This includes the development of different models to bridge the gap between mouse models and human patients. Emerging new tools to study inflammatory response owing to biomaterials and novel strategies for modulation of monocyte and macrophage behaviour in the wound environment are also discussed.

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Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells

Cited by 15 publications

References 63 publications

Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells

Generation and characterization of hair-bearing skin organoids from human pluripotent stem cells

Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy

Biomaterial mediated immunomodulation: An interplay of material environment interaction for ameliorating wound regeneration

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