Abstract
In my presentation, I will discuss our most recent insights into the pathogenesis of acne, the most common skin disease. Until recently, this condition was attributed to a mixture of increased skin oil production and bacterial overgrowth. It has become clear that these are outdated concepts that do not explain why acne develops, nor help us to develop any new treatments. Insights from genetics and skin biology have now helped paved the way for a radical overhaul of our thinking about the condition. The new perspective has already led to the development of in-vitro models, and inspired an effort to identify novel drug targets.
In my presentation, I will discuss our most recent insights into the pathogenesis of acne, the most common skin disease. Until recently, this condition was attributed to a mixture of increased skin oil production and bacterial overgrowth. It has become clear that these are outdated concepts that do not explain why acne develops, nor help us to develop any new treatments. Insights from genetics and skin biology have now helped paved the way for a radical overhaul of our thinking about the condition. The new perspective has already led to the development of in-vitro models, and inspired an effort to identify novel drug targets.
Bio
Maurice van Steensel studied medicine at the University of Nijmegen (the Netherlands) obtaining his MD in 1996. During his study, he was active in clinical genetics research and trained in molecular genetics. After graduating, he completed a cum laude PhD in genetics and dermatology, whilst training to become a dermatologist.In 2006, Dr van Steensel completed his dermatology training and in 2008 became associate professor and vice-chair of the department of Dermatology in Maastricht. He was appointed full professor in 2010 and joined the Institute of Medical Biology, Singapore as a Senior Principal Investigator in February, 2014. In January 2015, Professor Maurice became professor of Dermatology in the School of Medicine, University of Dundee, United Kingdom. In November 2015, he was appointed Honorary Visiting Professor in Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Professor Maurice joined the Skin Research Institute of Singapore full-time as a founding Research Director in June, 2017 and Lee Kong Chian School of Medicine as a full Professor in September of that year.
He is an internationally renowned expert in genetic skin disorders with over two decades of clinical and research experience in the field. His published work runs the gamut from clinical trials to ciliary biology. His present research focuses on the identification of novel active compounds for treating skin conditions.
Maurice van Steensel studied medicine at the University of Nijmegen (the Netherlands) obtaining his MD in 1996. During his study, he was active in clinical genetics research and trained in molecular genetics. After graduating, he completed a cum laude PhD in genetics and dermatology, whilst training to become a dermatologist.In 2006, Dr van Steensel completed his dermatology training and in 2008 became associate professor and vice-chair of the department of Dermatology in Maastricht. He was appointed full professor in 2010 and joined the Institute of Medical Biology, Singapore as a Senior Principal Investigator in February, 2014. In January 2015, Professor Maurice became professor of Dermatology in the School of Medicine, University of Dundee, United Kingdom. In November 2015, he was appointed Honorary Visiting Professor in Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. Professor Maurice joined the Skin Research Institute of Singapore full-time as a founding Research Director in June, 2017 and Lee Kong Chian School of Medicine as a full Professor in September of that year.
He is an internationally renowned expert in genetic skin disorders with over two decades of clinical and research experience in the field. His published work runs the gamut from clinical trials to ciliary biology. His present research focuses on the identification of novel active compounds for treating skin conditions.
Abstract
Sebaceous glands are one of the most important appendages of the skin with a critical role in skin homeostasis. Acne vulgaris is a common dermatological condition caused by multiple factors including the dysregulation of sebaceous glands. The aim of our work is to develop Sebaceous Gland Organoids (SGO) in 3D in vitro culture systems, which can be employed to better understand the mechanisms regulating sebaceous gland maintenance. To achieve this, a suitable matrix composition needs to be identified. Matrigel, a collagenous extract of mouse origin, has been commonly used as a hydrogel for the development of cell spheroids and organoids. However, the xenogeneic origin of Matrigel strongly limits its clinical acceptance. Hence, we formulated a matrix hydrogel that is suitable as an alternative to Matrigel, that supports the growth, maturity, and long-term expansion of mouse SGO. Over a 14-day culture period, the mouse SGO exhibited growth in size and maintained a central lumen filled with sebum lipids, which is characteristic of sebaceous glands in vivo. We adapted the hydrogel system for growing human SGO and found that the average size of these was larger than those developed in Matrigel. The human SGO also showed a more pronounced lipid core compared to those in Matrigel. In order to produce an array that could support high throughput drug screening for mechanistic studies or acne management, we used a 3D bioprinter to print regular sized droplets of hydrogel containing either mouse or human sebocytes. The rate of hydrogel crosslinking was optimized to allow smooth printing while keeping the cells, and eventually the SGO, suspended in a 3D environment. The SGO established through this bioprinting process displayed similar characteristics compared to those cultured manually. Overall, we successfully identified a suitable hydrogel matrix and optimized culture methods for mouse and human SGO production, and adapted this into a printable array for compound screening.
Sebaceous glands are one of the most important appendages of the skin with a critical role in skin homeostasis. Acne vulgaris is a common dermatological condition caused by multiple factors including the dysregulation of sebaceous glands. The aim of our work is to develop Sebaceous Gland Organoids (SGO) in 3D in vitro culture systems, which can be employed to better understand the mechanisms regulating sebaceous gland maintenance. To achieve this, a suitable matrix composition needs to be identified. Matrigel, a collagenous extract of mouse origin, has been commonly used as a hydrogel for the development of cell spheroids and organoids. However, the xenogeneic origin of Matrigel strongly limits its clinical acceptance. Hence, we formulated a matrix hydrogel that is suitable as an alternative to Matrigel, that supports the growth, maturity, and long-term expansion of mouse SGO. Over a 14-day culture period, the mouse SGO exhibited growth in size and maintained a central lumen filled with sebum lipids, which is characteristic of sebaceous glands in vivo. We adapted the hydrogel system for growing human SGO and found that the average size of these was larger than those developed in Matrigel. The human SGO also showed a more pronounced lipid core compared to those in Matrigel. In order to produce an array that could support high throughput drug screening for mechanistic studies or acne management, we used a 3D bioprinter to print regular sized droplets of hydrogel containing either mouse or human sebocytes. The rate of hydrogel crosslinking was optimized to allow smooth printing while keeping the cells, and eventually the SGO, suspended in a 3D environment. The SGO established through this bioprinting process displayed similar characteristics compared to those cultured manually. Overall, we successfully identified a suitable hydrogel matrix and optimized culture methods for mouse and human SGO production, and adapted this into a printable array for compound screening.
Bio
A/Prof Ng Kee Woei was a recipient of the A*STAR Graduate Scholarship. Prior to joining NTU, he was a Senior Research Fellow at the Institute of Medical Biology, A*STAR. In 2010, he began his tenure-track Assistant Professor position at the School of Materials Science and Engineering, NTU, and was promoted to the position of Associate Professor with tenure in 2015. A/Prof Ng’s research interests are highly interdisciplinary. In the area of sustainable nanotechnology, he is interested in understanding the implications of exposure to engineered nanomaterials in various scenarios. Through understanding of nanomaterial behaviour, transformation and interaction with biological systems, his group targets to develop nanotechnologies that are safe to use for both humans and the environment. In the area of biomaterials development, he is recognized for developing novel human hair keratin based platforms for various applications, including tissue engineering and regenerative medicine. His group has now developed the expertise to extract and process human hair keratins into various 2D and 3D templates including coatings, gels, sponges and electrospun mats. This are being explored for a range of biomedical applications such as skin regeneration, tendon repair, RPE cell delivery and bio-inks for 3D printing.
A/Prof Ng Kee Woei was a recipient of the A*STAR Graduate Scholarship. Prior to joining NTU, he was a Senior Research Fellow at the Institute of Medical Biology, A*STAR. In 2010, he began his tenure-track Assistant Professor position at the School of Materials Science and Engineering, NTU, and was promoted to the position of Associate Professor with tenure in 2015. A/Prof Ng’s research interests are highly interdisciplinary. In the area of sustainable nanotechnology, he is interested in understanding the implications of exposure to engineered nanomaterials in various scenarios. Through understanding of nanomaterial behaviour, transformation and interaction with biological systems, his group targets to develop nanotechnologies that are safe to use for both humans and the environment. In the area of biomaterials development, he is recognized for developing novel human hair keratin based platforms for various applications, including tissue engineering and regenerative medicine. His group has now developed the expertise to extract and process human hair keratins into various 2D and 3D templates including coatings, gels, sponges and electrospun mats. This are being explored for a range of biomedical applications such as skin regeneration, tendon repair, RPE cell delivery and bio-inks for 3D printing.
Chairs
Etienne Wang, NSC
Leah Vardy, SRIS
Etienne Wang, NSC
Leah Vardy, SRIS