Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model

Takagi, Ryo; Ishimaru, Junko; Sugawara, Ayaka; Toyoshima, Koh ei; Ishida, Kentaro; Ogawa, Miho; Sakakibara, Kooko; Asakawa, Kyosuke; Kashiwakura, Akitoshi; Oshima, Masamitsu; Minamide, Ryohei; Sato, Akio; Yoshitake, Toshihiro; Takeda, Akiko; Egusa, Hiroshi; Tsuji, Takashi

doi:10.1126/sciadv.1500887

Cited by 87 publications

(78 citation statements)

References 49 publications

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“…Likewise, HF-bearing cysts arise when dissociated embryonic skin from various mammals, including humans, is subcutaneously transplanted in mice (Zheng et al, 2005b; 2010). More recently, a system for generating integumentary tissues was described in which mouse embryonic stem cell aggregates were partially differentiated and then placed in the kidney capsule of athymic mice (Takagi et al, 2016). Following transplantation, the aggregates preferentially differentiated into full-thickness skin layers in a cyst-like conformation and produced HFs.…”

Section: Discussionmentioning

confidence: 99%

“…Regardless of dermal origin, all skin types require the interplay of epithelial (epidermis) and mesenchymal (dermis) cells for terminal development and appendage formation. In animal models, rodent and human skin with HFs can be reconstituted by co-culturing mesenchymal cells with epithelial cells or, specifically, HF initiating dermal papilla (DP) cells (Asakawa et al, 2012; Chuong et al, 2007; Ehama et al, 2007; Ikeda et al, 2009; Nakao et al, 2007; Takagi et al, 2016; Toyoshima et al, 2012; Zheng et al, 2005a). However, a chemically defined means of generating folliculogenic skin from pluripotent stem cells (PSCs) in vitro has been intangible.…”

Section: Introductionmentioning

confidence: 99%

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Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids

et al. 2018

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Summary The mammalian hair follicle arises during embryonic development from coordinated interactions between the epidermis and dermis. It is currently unclear how to recapitulate hair follicle induction in pluripotent stem cell cultures for use in basic research studies or in vitro drug testing. To date, generation of hair follicles in vitro has only been possible using primary cells isolated from embryonic skin, cultured alone or in a co-culture with stem cell-derived cells, combined with in vivo transplantation. Here, we describe the derivation of skin organoids, constituting epidermal and dermal layers, from a homogeneous population of mouse pluripotent stem cells in a 3D culture. We show that skin organoids spontaneously produce de novo hair follicles in a process that mimics normal embryonic hair folliculogenesis. This in vitro model of skin development will be useful for studying mechanisms of hair follicle induction, evaluating hair growth or inhibitory drugs, and modeling skin diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids

et al. 2018

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“…Takashi Tsuji (RIKEN CDB, Japan) introduced bioengineered organ germs by combining mouse embryonic mesenchyme and epithelia in a tiny droplet in collagen gel and transplanting these into host animals. He reported successful generation of teeth, hair and salivary glands (Ogawa et al, 2013;Takagi et al, 2016;Yamamoto et al, 2016). Importantly, these tissues have functional nerve connections to the host animals.…”

Section: Organogenesismentioning

confidence: 99%

Human development, heredity and evolution

Nishinakamura

Takasato

2017

Development

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From March 27-29 2017, the RIKEN Center for Developmental Biology held a symposium entitled ‘Towards Understanding Human Development, Heredity, and Evolution' in Kobe, Japan. Recent advances in technologies including stem cell culture, live imaging, single-cell approaches, next-generation sequencing and genome editing have led to an expansion in our knowledge of human development. Organized by Yoshiya Kawaguchi, Mitinori Saitou, Mototsugu Eiraku, Tomoya Kitajima, Fumio Matsuzaki, Takashi Tsuji and Edith Heard, the symposium covered a broad range of topics including human germline development, epigenetics, organogenesis and evolution. This Meeting Review provides a summary of this timely and exciting symposium, which has convinced us that we are moving into the era of science targeted on humans.

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“…Bioprinting of skin with all the constituent cell types, appendages and hair follicles is the first challenge. Recently, a group of scientists from Japan reported fabricating bioengineered 3D skin with hair follicles and sebaceous glands [3], which is a remarkable achievement and a great leap to have fully functional bioprinted skin. Further research is needed to create functional skin with sufficient vascularization, innervation and functions such as touch sensation and perception.…”

Section: S Vijayavenkataramanmentioning

confidence: 99%